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1.	Larsson, Britt, et al. (författare) The prevalences of cytochrome c oxidase negative and superpositive fibres and ragged-red fibres in the trapezius muscle of female cleaners with and without myalgia and of female healthy controls 2000 Ingår i: Pain. - 1872-6623 .- 0304-3959. ; 84:2-3, s. 379-387 Tidskriftsartikel (refereegranskat)abstract The association of cytochrome c oxidase negative fibres (COX-negative) and ragged-red fibres (RR-fibres) with work related trapezius myalgia has been proposed. Hitherto studies have been small or without control groups. The aim of the present study was to investigate the prevalences of RR-fibres and COX-negative fibres in female cleaners with (n=25) and without (n=23) trapezius myalgia and in clinically healthy female teachers (n=21). The cleaners did mainly floor cleaning requiring monotonous loading on the trapezius muscle. A questionnaire covering background data and aspects of pain (prevalence, duration, intensity and influence on daily living) was answered. Biopsies were obtained from the trapezius muscle by an open surgical technique. The three groups did not differ in prevalence of COX-negative or COX-superpositive (i.e. type-I fibres with extremely strong brownish reaction in both the COX and SDH/COX stainings) fibres. The prevalence of COX-negative fibres was age dependent. Two subgroups of RR-fibres were present when stained for COX; COX-negative (73%) and COX-superpositive (26%) fibres. Forty-two percent of the COX-negative fibres were RR-fibres and 79% of the COX-superpositive were RR-fibres. A significantly (P=0.002) higher proportion of the COX-superpositive fibres in the cleaners were RR-fibres compared to the teachers. Multivariate regression analysis revealed that age, occupation as cleaner and a tender point in the trapezius were significantly associated with increased prevalences of RR-fibres; a cleaner with a tender point had a 4.35 higher prevalence of RR-fibres compared to a teacher without a tender point. No correlations between other pain related variables and prevalence of RR-fibres were noted. In conclusion, RR-fibres but not COX-negative or COX-superpositive fibres were correlated with cleaning work tasks and with a tender point in the trapezius.
2.	Amandusson, Åsa, 1974-, et al. (författare) Estrogen-induced alterations of spinal cord enkephalin gene expression 1999 Ingår i: Pain. - : Elsevier. - 0304-3959 .- 1872-6623. ; 83:2, s. 243-248 Tidskriftsartikel (refereegranskat)abstract Enkephalin-synthesizing neurons in the super®cial laminae of the spinal and trigeminal dorsal horn are critical components of the endogenous pain-modulatory system. We have previously demonstrated that these neurons display intracellular estrogen receptors, suggesting that estrogen can potentially influence their enkephalin expression. By using Northern blot, we now show that a bolus injection of estrogen results in a rapid increase in spinal cord enkephalin mRNA levels in ovariectomized female rats. Thus, 4 h after estrogen administration the enkephalin mRNA-expression in the lumbar spinal cord was on average 68% higher (P , 0:05) than in control animals injected with vehicle only. A small increase in the amount of enkephalin mRNA was also seen after 8 h (P , 0:05), whereas no difference between estrogen-injected and control animals was found after 24 h or at time periods shorter than 4 h. Taken together with the previous anatomical data, the present findings imply that estrogen has an acute effect on spinal opioid levels in areas involved in the transmission of nociceptive information.
3.	Berglund, Birgitta, et al. (författare) Quantitative and qualitative perceptual analysis of cold dysesthesia and hyperalgesia in fibromyalgia. 2002 Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 96:1-2, s. 177-87 Tidskriftsartikel (refereegranskat)abstract Somatosensory perception thresholds, perceived intensity, and quality of perceptions were assessed in 20 women with fibromyalgia syndrome (FMS) and in 20 healthy age-matched female controls. All patients and controls scaled perceived intensity and described perceived quality of randomized thermal (Thermotest) and tactile (von Frey filaments) stimulation. Perceived intensity was scaled by free-number magnitude estimation and interindividual comparability was accomplished by Master Scaling. Perceived quality was assessed by choosing verbal descriptors from a list. Thenar was used as a reference for each modality tested. All patients were able to reliably scale perceived intensity at thenar, as well as in pain-affected body areas. Perception thresholds for cold pain, heat pain, cold-pain tolerance and heat-pain tolerance were significantly lower in patients than controls. For cold and tactile stimulation, the master scaled perceived intensities were significantly higher in patients' pain-affected areas, whereas for warmth/heat stimulation, the intensities were significantly lower. In the qualitative perceptual analysis the most striking and significant finding was the aberration of cold-evoked perceptions in all patients: most stimuli in the range of 30-10 degrees C were reported as heat or other paresthetic or dysesthetic perceptions. The perceptual quality of warmth, and of touch, did not differ from the controls. Another aberration was observed in the nociceptive range of thermal and of tactile stimulation as significantly more frequent pain-related descriptors than in controls. This indicates a general nociceptive facilitation in addition to the lower thermal pain thresholds. The combination of cold hyperesthesia, cold dysesthesia, and multimodal hyperalgesia suggests a selective pathophysiology at a particular level of integration, possibly in the insular cortex. It is suggested that the aberrations revealed by the supraliminal sensory evaluation may be generic for FMS. Particularly, the aberrations established in all patients for perceived quality and intensity in the cold sensory channel may be an additional diagnostic criterion.
4.	Bergström, Gunnar, Professor, et al. (författare) Reliability and factor structure of the Multidimensional Pain Inventory--Swedish Language Version (MPI-S). 1998 Ingår i: Pain. - : LWW. - 0304-3959 .- 1872-6623. ; 75:1, s. 101-10 Tidskriftsartikel (refereegranskat)abstract The psychological assessment of chronic pain is often accomplished using questionnaires such as the (West Haven-Yale) Multidimensional Pain Inventory ((WHY)MPI) which is constructed to capture the multidimensionality of chronic pain. The (WHY)MPI theoretically originates from behavioural and cognitive behavioural theories of pain. It is divided into three parts and measures psychosocial and behavioural consequences of pain. This questionnaire has displayed satisfactory psychometric properties and translations of the original English version into German and Dutch have been demonstrated to be reliable and valid. The aim of this study was to test the reliability and factor structure of a Swedish translation of the (WHY)MPI, the MPI-S, and also to test the generalisability of the factor structure found for the (WHY)MPI. We performed analyses of internal consistency using Cronbach's alpha, and carried out a confirmatory factor analysis (CFA) employing LISREL-8 on a population of 682 patients suffering from chronic musculoskeletal pain. Test-retest analysis was accomplished on a sub-sample of 54 individuals taken from the aforementioned population. For sections 1 and 2 of the MPI-S the overall reliability and stability were good, and after the exclusion of four items, the factor structure was similar to other versions of the MPI. For section 3, despite removal of five questions, the proposed factor structure could not be replicated. This part of the inventory is designed to measure the extent of different types of activities, and our results suggest that this section may only be used for assessing general activity level. We conclude that, with a few adjustments, the analyses yielded satisfactory results for sections 1 and 2 of the MPI-S regarding its factor structure, reliability and generalisability. For section 3 the hypothesised factor structure could not be confirmed.
5.	Bergström, Gunnar, Professor, et al. (författare) The impact of psychologically different patient groups on outcome after a vocational rehabilitation program for long-term spinal pain patients 2001 Ingår i: Pain. - : LWW. - 0304-3959 .- 1872-6623. ; 93:3, s. 229-237 Tidskriftsartikel (refereegranskat)abstract A better knowledge of differential treatment outcomes for subgroups of chronic spinal pain patients may, for instance, help clinicians in treatment planning or pain researchers in treatment outcome research. The purpose of this prospective study was to evaluate the predictive validity of a subgroup classification based on the Swedish version of the (West Haven Yale) Multidimensional Pain Inventory, the MPI-S. Patients referred to a vocational rehabilitation program were classified into one of three groups, labeled ‘adaptive copers’, ‘dysfunctional’ patients, and ‘interpersonally distressed’ patients, and followed over an 18-month follow-up period. The outcome variables were absence from work (defined as sick listing plus early retirement), general health status, and utilization of health care resources. To our knowledge, the predictive validity of the MPI subgroups has not been evaluated regarding sick listing and early retirement after rehabilitation. As hypothesized, the results showed that the ‘dysfunctional’ patient group had significantly more registered absences from work and reported higher utilization of health care, over the follow-up period compared to the ‘adaptive copers’. Furthermore, as hypothesized, the ‘interpersonally distressed’ and ‘dysfunctional’ patient groups report a poorer general health status than the ‘adaptive copers’ over the whole follow-up period. However, contrary to our hypothesis, the proportion of improved patients did not differ significantly between the subgroups. Altogether, the predictive validity of the MPI-S subgroup classification was mainly confirmed. The clinical implications of this study suggest that the matching of treatment to patient needs may enhance treatment outcome, reduce pain and suffering among chronic spinal pain patients and facilitate a better health economic allocation of treatment resources.
6.	Brattberg, Gunilla, et al. (författare) The prevalence of pain among the oldest old in Sweden 1996 Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 67:1, s. 29-34 Tidskriftsartikel (refereegranskat)abstract Although there is information available about pain in elderly persons, there have been very few studies about pain among the oldest old. In Sweden, 8% of the population is older than 74 years, and 2% is older than 84 years. It is the group over 74 which is growing fastest in proportion to the entire population. The aims of the present study are (a) to analyze if pain increases or decreases with age in the oldest age groups and (b) to study gender differences regarding pain. The present study of a random sample (n = 537) of the oldest old in Sweden shows that there is some evidence of decreased musculoskeletal pain with age. Among women, total reported pain decreases with age. Among men, there is an increase of reported severe pain with age. Including the results from another Swedish population survey of individuals aged 18-84, there is evidence that the prevalence of pain among the older elderly is comparable to the prevalence of pain among the middle-aged (45-64) and is higher than the prevalence among the younger elderly (65-75). Musculoskeletal pain is more common among old women than old men but for chest pain and abdominal pain there is no difference. The sex difference is more pronounced for multiple and severe pain complaints. The prevalence of mild or severe pain in any of the studied locations in the whole study group (77+) was 73% and for individuals over 85 years, 68%. For multiple pain, the figures were 47% for all older elderly (77+) and 46% for individuals over 85 years of age. For severe pain in at least one location, corresponding figures were 33% and 35%.
7.	Buer, Nina, 1960-, et al. (författare) Fear-avoidance beliefs and catastrophizing : occurrence and risk factor in back pain and ADL in the general population 2002 Ingår i: Pain. - 0304-3959 .- 1872-6623. ; 99:3, s. 485-491 Tidskriftsartikel (refereegranskat)abstract Fear-avoidance beliefs and catastrophizing have been shown to be powerful cognitions in the process of developing chronic pain problems and there is a need for increased knowledge in early stages of pain.The objectives of this study were therefore, firstly, to examine the occurrence of fear-avoidance beliefs and catastrophizing in groups with different degrees of non-chronic spinal pain in a general population, and secondly to assess if fear-avoidance beliefs and catastrophizing were related to current ratings of pain and activities of daily living (ADL).The study was a part of a population based back pain project and the study sample consisted of 917 men and women, 35-45 years old, either pain-free or with non-chronic spinal pain. The results showed that fear-avoidance beliefs as well as catastrophizing occur in this general population of non-patients. The levels were moderate and in catastrophizing a 'dose-response' pattern was seen, such that more the catastrophizing was, the more was pain. The study showed two relationships, which were between fear-avoidance and ADL as well as between catastrophizing and pain intensity. Logistic regression analyses were performed with 95% confidence intervals and the odds ratio for fear-avoidance beliefs and ADL was 2.5 and for catastrophizing and pain 1.8, both with confidence interval above unity. The results suggest that fear-avoidance beliefs and catastrophizing may play an active part in the transition from acute to chronic pain and clinical implications include screening and early intervention. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.
8.	Craig, AD, et al. (författare) Association of spinothalamic lamina I neurons and their ascending axons with calbindin-immunoreactivity in monkey and human 2002 Ingår i: Pain. - 0304-3959 .- 1872-6623. ; 97:1-2, s. 105-115 Tidskriftsartikel (refereegranskat)abstract The calbindin-immunoreactivity of spinothalamic (STT) lamina I neurons and their ascending axons was examined in two experiments. In the first experiment, lamina I STT neurons in macaque monkeys were double-labeled for calbindin and for retrogradely transported WGA*HRP following large (n=2) or small (n=1) injections that included the posterior thalamus. Most, but not all (78%) of the contralateral retrogradely labeled lamina I STT cells were positive for calbindin. Calbindin-immunoreactivity was not selectively associated with any particular anatomical type of lamina I STT cell, 82% of the fusiform cells, 78% of the pyramidal cells and 67% of the multipolar cells were double-labeled. In the second experiment, oblique transverse sections from upper cervical spinal segments of three macaque monkeys, one squirrel monkey and five humans were stained for calbindin-immunoreactivity. In each case, a distinct bundle of fibers was densely stained in the middle of the lateral funiculus. This matches the location of anterogradely labeled ascending lamina I axons observed in prior work in cats and monkeys, and it matches the location of the classically described 'lateral spinothalamic tract' in humans. This bundle had variable shape across cases, an observation that might have clinical significance. These findings support the view that lamina I STT neurons are involved in spinal cordotomies that reduce pain, temperature and itch sensations. ⌐ 2002 International Association for the study of Pain. Published by Elsevier Science B.V. All rights reserved.
9.	Graven-Nilsen, T, et al. (författare) Ketamine reduces muscle pain, temporal summation, and referred pain in fibromyalgia patients 2000 Ingår i: Pain. - 0304-3959 .- 1872-6623. ; 85:3, s. 483-491 Tidskriftsartikel (refereegranskat)abstract Central mechanisms related to referred muscle pain and temporal summation of muscular nociceptive activity are facilitated in fibromyalgia syndrome (FMS) patients. The present study assessed the effects of an NMDA-antagonist (ketamine) on these central mechanisms. FMS patients received either i.v. placebo or ketamine (0.3 mg/kg, Ketalar(«)) given over 30 min on two separate occasions. Habitual pain intensity was assessed on a visual analogue scale (VAS). Initially, 29 FMS patients received ketamine or isotonic saline to determine which patients were ketamine responders (>50% decrease in pain intensity at rest by active drug on two consecutive VAS assessments). Fifteen out of 17 ketamine-responders were included in the second part of the study. Before and after ketamine or placebo, experimental local and referred pain was induced by intramuscular (i.m.) infusion of hypertonic saline (0.7 ml, 5%) into the tibialis anterior (TA) muscle. The saline-induced pain intensity was assessed on an electronic VAS, and the distribution of pain drawn by the subject. In addition, the pain threshold (PT) to i.m. electrical stimulation was determined for single stimulus and five repeated (2 Hz, temporal summation) stimuli. The pressure PT of the TA muscle was determined, and the pressure PT and pressure pain tolerance threshold were determined at three bilaterally located tenderpoints (knee, epicondyle, and mid upper trapezius). VAS scores of pain at rest were progressively reduced during ketamine infusion compared with placebo infusion. Pain intensity (area under the VAS curve) to the post-drug infusion of hypertonic saline was reduced by ketamine (-18.4▒0.3% of pre-drug VAS area) compared with placebo (29.9▒18.8%, P<0.02). Local and referred pain areas were reduced by ketamine (-12.0▒14.6% of pre-drug pain areas) compared with placebo (126.3▒83.2%, P<0.03). Ketamine had no significant effect on the PT to single i.m. electrical stimulation. However, the span between the PT to single and repeated i.m. stimuli was significantly decreased by the ketamine (-42.3▒15.0% of pre-drug PT) compared with placebo (50.5▒49.2%, P<0.03) indicating a predominant effect on temporal summation. Mean pressure pain tolerance from the three paired tenderpoints was increased by ketamine (16.6▒6.2% of pre-drug thresholds) compared with placebo (-2.3▒4.9%, P<0.009). The pressure PT at the TA muscle was increased after ketamine (42.4▒9.2% of pre-drug PT) compared with placebo (7.0▒6.6%, P<0.011). The present study showed that mechanisms involved in referred pain, temporal summation, muscular hyperalgesia, and muscle pain at rest were attenuated by the NMDA-antagonist in FMS patients. It suggested a link between central hyperexcitability and the mechanisms for facilitated referred pain and temporal summation in a sub-group of the fibromyalgia syndrome patients. Whether this is specific for FMS patients or a general phenomena in painful musculoskeletal disorders is not known. Copyright (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V.
10.	Grossi et al, G, et al. (författare) Psychosocial correlates of long-term sick-leave among patients with musculoskeletal pain 1999 Ingår i: Pain. - 0304-3959 .- 1872-6623. ; 80:3, s. 607-620 Tidskriftsartikel (refereegranskat)
11.	Jensen, Irene B., et al. (författare) A randomized controlled component analysis of a behavioral medicine rehabilitation program for chronic spinal pain: are the effects dependent on gender? 2001 Ingår i: Pain. - : LWW. - 0304-3959 .- 1872-6623. ; 91:1, s. 65-78 Tidskriftsartikel (refereegranskat)abstract The aim of the present study was to evaluate the outcome of a behavioral medicine (BM) rehabilitation program and the outcome of its two main components, compared to a ‘treatment-as-usual’ control group (CG). The study employed a 4×4 repeated-measures design with four groups and four assessment periods (pre-treatment, post-treatment, 6-month follow-up, and 18-month follow-up). The group studied consisted of subjects on sick leave identified in a nationwide health insurance scheme in Sweden. After inclusion, the subjects were randomized to one of four conditions, which were: (1) behavior-oriented physical therapy (PT); (2) cognitive behavioral therapy (CBT); (3) BM rehabilitation consisting of PT+CBT (BM); (4) a ‘treatment-as-usual’ CG. The treatments were given over a period of 4 weeks, PT and CBT on a part-time basis and BM on a full-time basis. Outcome variables were sick leave, early retirement, and health-related quality of life (measured using the Short Form Health Survey, SF-36). The results showed that the risk of being granted full-time early retirement was significantly lower for females in PT and CBT compared to the CG during the 18-month follow-up period. However, the total absence from work (sick listing plus early retirement) in days over the 18-month follow-up period was not significantly different in the CG compared to the treatments. On the SF-36, women in CBT and BM reported a significantly better health-related quality of life than women in the CG at the 18-month follow-up. No significant differences for men were found on the SF-36 scales. In conclusion, the results revealed gender differences in the outcome of the treatments and that the components of this BM program yielded as good results as the whole program.
12.	Koltzenburg, M, et al. (författare) Dynamic and static components of mechanical hyperalgesia in human hairy skin 1992 Ingår i: Pain. - : Elsevier BV. - 0304-3959 .- 1872-6623. ; 51:2, s. 207-219 Tidskriftsartikel (refereegranskat)abstract The principle finding of the present study is that there are two types of mechanical hyperalgesia developing in human hairy skin following injurious stimuli. Mechanical hyperalgesia comprises a dynamic component (brush-evoked pain, allodynia) signalled by large myelinated afferents and a static component (hyperalgesia to pressure stimuli) signalled by unmyelinated afferents. While the static component is only found in the injured area, the dynamic component also extends into a halo of undamaged tissue surrounding the injury. The irritant chemicals, mustard oil or capsaicin, were applied transdermally in 20 subjects to a patch (2 × 2 cm) of hairy skin. Both substances evoked burning pain and hyperalgesia to mechanical stimuli. While stroking normal skin with a cotton bud was perceived only as touch prior to chemical stimulation, there was a distinctly unpleasant sensation afterwards. This component of mechanical hyperalgesia persisted for at least 30 min and was present in the skin exposed to the irritants (primary hyperalgesia) as well as in a zone of untreated skin surrounding the injury (secondary hyperalgesia) measuring 38 ± 4 cm2 after capsaicin. Pressure pain thresholds dropped to 55 ± 8% of baseline level after mustard oil and to 46 ± 9% after capsaicin. However, this drop of thresholds was short-lived, lasting 5 min following mustard oil but persisting more than 30 min following capsaicin treatment. The reduction of pressure pain thresholds was only observed for treated skin areas, but not in the surrounding undamaged tissue from where brush-evoked pain could be evoked. When pressure pain thresholds were lowered, the pain had a burning quality which differed distinctly from the quality of brush-evoked pain. On-going burning pain and both types of mechanical hyperalgesia were critically temperature dependent. Mildly cooling the skin provided instant relief from on-going pain, abolished brush-evoked pain and normalized pressure pain thresholds. Rewarming resulted in a reappearence of on-going pain and hyperalgesia. The effect of a nerve compression block of the superficial radial nerve on these sensations was tested in 14 experiments. When the ability to perceive light touch had been abolished, there was also no touch-evoked pain, indicating that this component of mechanical hyperalgesia is mediated by large-diameter primary afferents. At a later stage of the block when the subjects' ability to perceive cold stimuli had also been lost, application of cool stimuli still eliminated on-going burning pain, suggesting that pain relief afforded by cooling the skin acts at the peripheral receptor level and not by central masking. Importantly, at this stage of the block, when only unmyelinated primary afferents conducted, neither spontaneous pain, nor hyperalgesia to heat, nor the lowered pressure pain threshold had changed significantly. Based on the differences in quality of sensations, in spatial and temporal profiles and in susceptibility to differential nerve blocks, we conclude that irritant chemicals induce a dynamic and static component of mechanical hyperalgesia signalled by large-diameter or unmyelinated fibres, respectively. While the static component may be mediated by sensitized peripheral nociceptors, the dynamic component is probably the consequence of an altered processing of large diameter primary afferent input in the central nervous system subsequent to a maintained barrage of nociceptor activity. The parallel fluctuation of brush-evoked and burning background pain therefore suggest that on-going activity from nociceptors is required to maintain a central state that permits dynamic mechanical hyperalgesia to be expressed in humans.
13.	Kosek, Eva, et al. (författare) Lack of pressure pain modulation by heterotopic noxious conditioning stimulation in patients with painful osteoarthritis before, but not following, surgical pain relief. 2000 Ingår i: Pain. - 0304-3959 .- 1872-6623. ; 88:1, s. 69-78 Tidskriftsartikel (refereegranskat)abstract To investigate the influence of chronic nociceptive pain on endogenous pain modulation, the effect of heterotopic noxious conditioning stimulation (HNCS) on perception of various somatosensory modalities was assessed in 15 patients with painful osteoarthritis of the hip. Thirteen patients were re-assessed when pain-free 6-14 months following surgery. Sex- and age matched healthy subjects assessed at similar time intervals served as controls. The effects of HNCS were tested using the upper extremity submaximal effort tourniquet test. Subjects rated tourniquet-induced pain intensity on a visual analogue scale (VAS). Quantitative sensory testing (QST) was performed contralaterally to the maximally painful area in 13 patients and contralaterally to the second most painful area in two patients (i.e. lateral thigh n = 12, frontal thigh n = 1, lateral calf n = 2). Sensibility was assessed before, during and 45 min following the tourniquet test. Perception thresholds to light touch were assessed using von Frey filaments and pressure pain thresholds by pressure algometry. Perception thresholds to non-painful and painful warmth and cold were determined using a Thermotest. In both sessions, patients rated the tourniquet-induced pain higher than controls at the start (P < 0.003 and P < 0.006, respectively), but not at the end of the tourniquet test. Decreased sensitivity to light touch (P < 0.001) and innocuous cold (P < 0.002) was seen during the tourniquet in patients and controls alike, on both occasions, while perception thresholds to innocuous warmth and heat pain remained unaffected. In the first session, pressure pain thresholds increased during the tourniquet test in controls (P < 0.002), but not in patients. In the second session, pressure pain thresholds increased during the tourniquet test in controls (P < 0.001) and in patients (P < 0.02). In conclusion, no pressure pain modulation was induced by HNCS in patients before surgery, as opposed to controls, suggesting a dysfunction in systems subserving 'diffuse noxious inhibitory controls' (DNIC). Normal pressure pain modulation induced by HNCS was seen when patients were re-assessed in a pain-free state following surgery, indicating that the dysfunction of DNIC had been maintained by chronic nociceptive pain.
14.	Kosek, Eva, et al. (författare) Modulation of pressure pain thresholds during and following isometric contraction. 1995 Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 61:3, s. 481-486 Tidskriftsartikel (refereegranskat)abstract This study aimed at evaluating the influence of submaximal isometric contraction on pressure pain thresholds (PPTs) in 14 healthy volunteers before and after skin hypoesthesia. PPTs were determined with pressure algometry over m. quadriceps femoris before, during, and following an isometric contraction. Maximum voluntary contraction (MVC) was assessed using a computerized dynamometer. A contraction of 21% MVC was held until exhaustion (max: 5 min) and PPTs were assessed every 30 sec. A local anesthetic cream and a control cream were applied following a double-blind design and PPTs were reassessed. PPTs increased significantly at the start of contraction and continued to increase until the middle of the contraction period, then remaining at this level. After contraction PPTs decreased significantly but for 5 min remained slightly above precontraction levels. Anesthetic cream raised PPT at rest but not during and following contraction. The relative increase in PPTs during and immediately following isometric contraction was lower with anesthetic cream. Isometric contraction of m. quadriceps femoris increase PPTs during and following contraction. The results suggest that input from cutaneous and deeper tissues interacts with nociceptive activity set up by the pressure stimulus. Determining the degree of sensory modulation in muscle and skin in different chronic pain syndromes could become a functional method of patient assessment important for differential diagnosis, treatment evaluation, and follow-up.
15.	Kosek, Eva, et al. (författare) Modulation of pressure pain thresholds during and following isometric contraction in patients with fibromyalgia and in healthy controls. 1996 Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 64:3, s. 415-423 Tidskriftsartikel (refereegranskat)abstract This study aimed at evaluating the influence of submaximal isometric contraction on pressure pain thresholds (PPTs) in 14 fibromyalgia (FM) patients and 14 healthy volunteers, before and after skin hypoesthesia. PPTs were determined with pressure algometry over m. quadriceps femoris before, during and following an isometric contraction. Maximum voluntary contraction (MVC) was assessed using a computerized dynamometer. A contraction of 22% MVC on average was held until exhaustion (max. 5 min) and PPTs were assessed every 30 sec. A local anesthetic cream and a control cream were applied following a double-blind design and PPTs were reassessed. In healthy volunteers PPTs increased during contraction (P < 0.001), then decreased after the end of contraction (P < 0.001) but remained above precontraction values during the 5 min of post-contraction assessments (P < 0.001). In FM patients PPTs decreased in the middle of the contraction period (P < 0.05) and remained below precontraction levels during the rest of the contraction period (P < 0.05) and during the 5 min of post-contraction assessment (immediately post-contraction NS; 2.5 min post-contraction P < 0.01; 5 min post-contraction P < 0.05). The normalized PPTs were significantly lower in patients than in controls during contraction (start P < 0.01; middle P < 0.001; end P < 0.001) and at all times during post-contraction assessments (P < 0.001). Anesthetic cream raised PPTs at rest in controls (P < 0.01) but not in FM patients, and did not influence contraction or post-contraction PPTs in either group. Therefore, the increased pressure pain sensibility in FM patients is more pronounced deep to the skin. The observed decrease of PPTs during isometric contraction in FM patients could be due to sensitization of mechanonociceptors caused by muscle ischemia and/or dysfunction in pain modulation during muscle contraction.
16.	Kosek, E, et al. (författare) Modulatory influence on somatosensory perception from vibration and heterotopic noxious conditioning stimulation (HNCS) in fibromyalgia patients and healthy subjects. 1997 Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 70:1, s. 41-51 Tidskriftsartikel (refereegranskat)abstract In order to assess the function of endogenous mechanisms modulating somatosensory input in fibromyalgia (FM), the effect of vibratory stimulation (VS) and heterotopic noxious conditioning stimulation (HNCS) on perception of various somatosensory modalities was assessed. Ten female FM patients and 10 healthy, age-matched, females participated. VS (100 Hz) was applied to the left forearm for 45 min and quantitative sensory testing (QST) was performed within the vibrated area and in the right thigh before, during and 45 min following vibration. Pressure pain thresholds (PPTs) were assessed by pressure algometry. Perception thresholds to non-painful cold (CT) and warmth (WT), heat pain thresholds (HPTs), cold pain thresholds (CPTs) and stimulus-response curves of pain intensity as a function of graded nociceptive heat stimulation were assessed using a Peltier element based thermal stimulator. The effects of HNCS were tested using the upper extremity submaximal effort tourniquet test. Subjects rated tourniquet induced pain intensity on a visual analogue scale (VAS). QST was performed in the right thigh before, during and 60 min following the tourniquet. FM patients did not differ from controls in the response to VS. There was a local increase of PPTs during vibration (P < 0.001) and of WTs following vibration (P < 0.001). HPTs increased in the forearm and in the thigh (P < 0.009) during vibration. CTs and sensitivity to suprathreshold heat pain were not influenced by VS. The intensity of pain induced by the tourniquet did not differ between groups. PPTs increased during the tourniquet in controls (P < 0.001) but not in FM patients (difference between groups P < 0.001). Decreased sensitivity to non-painful cold (P < 0.001) and non-painful warmth (P < 0.001) was seen during and following (P < 0.001; P < 0.05, respectively) the tourniquet in both groups alike. HPTs and perception of suprathreshold heat pain remained unaffected in both groups. In conclusion, FM patients did not differ from healthy controls in their response to vibration, but no modulation of pressure pain was induced by HNCS, as opposed to controls, suggesting a dysfunction in systems subserving 'diffuse noxious inhibitory controls' (DNIC).
17.	Kosek, Eva, et al. (författare) Perceptual integration of intramuscular electrical stimulation in the focal and the referred pain area in healthy humans. 2003 Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 105:1-2, s. 125-31 Tidskriftsartikel (refereegranskat)abstract The aim of the study was to investigate the perceptual integration of simultaneous stimulation in a focal and a referred pain area to investigate whether referred pain is mainly caused by facilitation of on-going input from the referred pain area by stimulation in the focal pain area or if referred pain is a consequence of misinterpretation of the origin of inputs from the focal pain area. Pain was induced in twelve healthy individuals by intramuscular electrical stimulation in the left infraspinatus muscle (MI) or the left dorsolateral upper arm (UA), i.e. the area of referral commonly reported from stimulation in MI. Conditioning stimulation consisted of, in a counterbalanced order, no stimulation (baseline) and pain intensity rated as 2/10 and 4/10, respectively, on a category scale. During conditioning stimulation in MI, sensitivity to test stimuli was assessed in UA and vice versa. The test stimuli consisted of i.m. electrical stimulation corresponding to the perception threshold to innocuous electrical stimulation, the electrical pain threshold (EPT), and pain intensity rated as 2/10, 4/10 and 6/10, respectively. Conditioning stimulation corresponding to 2/10 did not result in a statistically significant change in sensitivity to any test stimuli in either location. During conditioning stimulation corresponding to 4/10 in m. infraspinatus, all twelve subjects reported referred pain in the dorsolateral upper arm. Compared to baseline, EPTs decreased in the referred pain area (P<0.001), while no other statistically significant changes in sensitivity to test stimuli were seen. Conditioning stimulation corresponding to 4/10 in the dorsolateral upper arm gave rise to referred pain in one individual (area of m. biceps brachii), and no statistically significant changes were seen in the sensitivity to electrical stimuli in m. infraspinatus. In conclusion, an effect at pain threshold level only was documented during simultaneous stimulation in the focal and referred pain area, which does not support facilitation of inputs from the referred pain area as the main mechanism generating referred pain. Instead, referred pain is most likely a consequence of misinterpretation of the origin of input from the stimulated focal pain area, due to excitation of neurones somewhere along the neuroaxis with projected fields in the referred pain area. The fact that conditioning stimulation in m. infraspinatus generated referred pain in the dorsolateral upper arm, but not vice versa suggests that the divergence of the input is not reciprocally arranged.
18.	Kosek, E, et al. (författare) Sensory dysfunction in fibromyalgia patients with implications for pathogenic mechanisms. 1996 Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 68:2-3, s. 375-83 Tidskriftsartikel (refereegranskat)abstract This study, addressing etiologic and pathogenic aspects of fibromyalgia (FM), aimed at examining whether sensory abnormalities in FM patients are generalized or confined to areas with spontaneous pain. Ten female FM patients and 10 healthy, age-matched females participated. The patients were asked to rate the intensity of ongoing pain using a visual analogue scale (VAS) at the site of maximal pain, the homologous contralateral site and two homologous sites with no or minimal pain. Quantitative sensory testing was performed for assessment of perception thresholds in these four sites. Von Frey filaments were used to test low-threshold mechanoreceptive function. Pressure pain sensitivity was assessed with a pressure algometer and thermal sensitivity with a Thermotest. In addition the stimulus-response curve of pain intensity as a function of graded nociceptive heat stimulation was studied at the site of maximal pain and at the homologous contralateral site. FM patients had increased sensitivity to non-painful warmth (P < 0.01) over painful sites and a tendency to increased sensitivity to non-painful cold (P < 0.06) at all sites compared to controls, but there was no difference between groups regarding tactile perception thresholds. Compared to controls, patients demonstrated increased sensitivity to pressure pain (P < 0.001), cold pain (P < 0.001) and heat pain (P < 0.02) over all tested sites. The stimulus-response curve was parallely shifted to the left of the curve obtained from controls (P < 0.003). Intragroup comparisons showed that patients had increased sensitivity to pressure pain (P < 0.01) and light touch (P < 0.05) in the site of maximal pain compared to the homologous contralateral site. These findings could be explained in terms of sensitization of primary afferent pathways or as a dysfunction of endogenous systems modulating afferent activity. However, the generalized increase in sensitivity found in FM patients was unrelated to spontaneous pain and thus most likely due to a central nervous system (CNS) dysfunction. The additional hyperphenomena related to spontaneous pain are probably dependent on disinhibition/facilitation of nociceptive afferent input from normal (or ischemic) muscles.
19.	Kåreholt, Ingemar, et al. (författare) Pain and mortality risk among elderly persons in Sweden 1998 Ingår i: Pain. - 0304-3959 .- 1872-6623. ; 77:3, s. 271-278 Tidskriftsartikel (refereegranskat)abstract The aim of this study is to analyse how the mortality risk varies with mild or severe pain in different locations: chest, back and hips, shoulders, the extremities, abdomen, rectum and head. A Swedish nationally representative sample of 1930 persons born 1892-1915 were interviewed in 1968 (ages 53-76). Survivors were also interviewed in 1974 and 1981 if they had not passed the age of 75 years. Proportional hazard regression was used to analyze mortality risk among persons ages 53-98 years for the period 1968-1991. Relationships were found between mortality risk and headache, chest pain, abdominal pain, pain in the extremities and rectal pain. No relationships were found between mortality and pain in back and hips or in shoulders. There was a correlation between chest pain and increased mortality among both men and women, but the association was significantly stronger among men. There was a significant association between severe rectal pain and mortality among men but no similar association among women. Significant associations between mortality and chest pain and abdominal pain were found among persons younger than 80 years, but not among those older than 80 years. Pain is an indicator of the quality of life and a symptom of underlying medical conditions. The finding that there are relationships between mortality risk and pain in the chest, abdomen, rectum, the extremities and head may be of clinical relevance. These results, however, must be further investigated since the relationships between reported pain and mortality do not imply that pain in these locations is necessarily symptomatic of lethal diseases. Abdominal pain, rectal pain and headache may be indicators of diseases but can also be side effects of treatments for other diseases correlated with higher mortality.
20.	Linton, Steven J., 1952-, et al. (författare) A controlled study of the effects of an early intervention on acute musculoskeletal pain problems 1993 Ingår i: Pain. - : Elsevier. - 0304-3959 .- 1872-6623. ; 54:3, s. 353-359 Tidskriftsartikel (refereegranskat)abstract Current conceptions of chronic pain clearly suggest that proper care at the acute stage should prevent the development of chronic problems. Patients (198) seeking help for acute musculoskeletal pain (MSP), e.g., back and neck pain participated in two studies of the effects of an Early Active intervention which underscored 'well' behavior and function compared to a Treatment as Usual control group. The quantity of the Early Active treatment was a median of 1 doctor's appointment and 3 meetings with a physical therapist. Study I concerned patients with a prior history of sick-listing for MSP, while study II involved patients with no prior history of MSP. Treatment satisfaction, pain experience, activities and sickness absenteeism were assessed before, after and at a 12-month follow-up. In study I (patients with a history of MSP), the results showed significant improvements for both groups, but virtually no differences between the groups. Similarly, in study II (no history of MSP) both groups demonstrated significant improvements e.g., for pain intensity and activity levels. However, the Early Active treatment resulted in significantly less sick-listing relative to the control group. Moreover, the risk of developing chronic (> 200 sick days) pain was 8 times lower for the Early Activation group. This investigation shows that relatively simple changes in treatment result in reduced sickness absenteeism for 'first-time' sufferers only. Consequently, the content and timing of treatment for pain appear to be crucial. Properly administered early intervention may therefore decrease sick leave and prevent chronic problems, thus saving considerable resources.
21.	Linton, Steven J., 1952-, et al. (författare) The secondary prevention of low back pain : a controlled study with follow-up 1989 Ingår i: Pain. - : Elsevier. - 0304-3959 .- 1872-6623. ; 36:2, s. 197-207 Tidskriftsartikel (refereegranskat)abstract The current investigation studied the effectiveness of a secondary prevention program for nurses with back pain who were deemed at risk for developing a chronic problem. A 2 × 3 repeated measures design was employed with 2 groups and 3 assessment periods. The treatment group received an intervention designed to reduce current problems, but above all to prevent reinjury and minor pains from becoming chronic medical problems, and it included a physical and behavioral therapy package. The control group was placed on a waiting-list. Results indicated that the treatment group had significantly greater improvements than the control group for pain intensity, anxiety, sleep quality and fatigue ratings, observed pain behavior, activities, mood, and helplessness. These differences were generally maintained at the 6 month follow-up. In addition, the treatment group broke a trend for increasing amounts of pain-related absenteeism, while the control group did not. Taken as a whole, the results suggest that a secondary prevention program aimed at altering life style factors may represent an effective method for dealing with musculoskeletal pain problems.
22.	Linton, Steven J., 1952- (författare) The socioeconomic impact of chronic back pain : Is anyone benefiting? 1998 Ingår i: Pain. - : Wolters Kluwer. - 0304-3959 .- 1872-6623. ; 75:2-3, s. 163-168 Tidskriftsartikel (refereegranskat)
23.	List, T., et al. (författare) Intra-articular morphine as analgesic in temporomandibular joint arthralgia/osteoarthritis 2001 Ingår i: Pain. - 0304-3959 .- 1872-6623. ; 94:3, s. 275-282 Tidskriftsartikel (refereegranskat)abstract The aim of this study was to determine the analgesic efficacy of a single dose intra-articular injection (i.a.) of morphine in 53 patients with unilateral arthralgia/osteoarthritis of the temporomandibular joint (TMJ). This randomized, double-blind, parallel group, multicenter study included a screening visit, a treatment visit, and a follow-up visit 1 week after treatment. Recordings of visual analog scales (VAS) pain intensity scores at maximum mouth opening (main efficacy variable) and at jaw rest were made directly before a 1-ml i.a. injection into one TMJ of either 1.0 mg morphine-HCl, 0.1 mg morphine-HCl, or saline (placebo). The pain intensity was also recorded at the follow-up and in a diary 3 days before and 5 days after the injection. The VAS pain score at maximum mouth opening was considerably reduced 1-10 h after injection but without significant differences between groups. At the follow-up, the median VAS pain score at maximal mouth opening was significantly lower in the 0.1-mg morphine group than in the 1.0-mg morphine group (P < 0.043) or the saline group (P < 0.021). A significant increase in pain pressure threshold over the affected joint was seen in the 0.1-mg morphine group compared with the saline group at the follow-up but not 1 and 2 h post-injection. The incidence of adverse events was small and did not differ between the treatment groups. In conclusion, one i.a. injection of 0.1 mg morphine significantly increased the pain pressure threshold and mouth opening ability, but evidence for the analgesic property of the locally applied opioid was inconclusive. No dose-effect relation and no significant short-term analgesic property were seen. Although statistically significant, the magnitude of the reduced VAS pain intensity score was not clinically relevant at the 1-week follow-up. © 2001 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.
24.	Marhold, Charlotta, et al. (författare) A cognitive-behavioral return-to-work program : Effects on pain patients with a history of long-term versus short-term sick leave 2001 Ingår i: Pain. - : Elsevier. - 0304-3959 .- 1872-6623. ; 91:1-2, s. 155-163 Tidskriftsartikel (refereegranskat)abstract A cognitive-behavioral return-to-work focused program was evaluated in a randomized controlled design, and the effects were compared between two groups of women with musculoskeletal pain. One group of patients (n=36) had a history of long-term sick leave (>12 months) at the start of the program and the other (n=36) had a history of short-term sick leave (2-6 months). The outpatient treatment program, conducted by a psychologist, included 12 sessions with the primary aim to help the patients return-to-work. The treatment first included teaching of coping strategies such as applied relaxation, stress management, graded activity training and pacing. Thereafter the patients were taught how to manage difficulties at their return-to-work and how to generalize coping strategies to different risk factors at their work places. The control condition received treatment-as-usual. The results showed that the cognitive-behavioral return-to-work program was more effective than the treatment-as-usual control condition in reducing the number of days on sick leave for patients on short-term sick leave, but not for patients on long-term sick leave. The treatment program also helped the patients on short-term sick leave to increase their ability to control and decrease pain and to increase their general activity level compared to the control condition. These results underscore the need for an early return-to-work focused rehabilitation to prevent long-term sick leave and disability.
25.	Svensson, P., et al. (författare) Analysis of stimulus-evoked pain in patients with myofascial temporomandibular pain disorders 2001 Ingår i: Pain. - 0304-3959 .- 1872-6623. ; 92:3, s. 399-409 Tidskriftsartikel (refereegranskat)abstract The pathophysiological mechanisms of myofascial temporomandibular disorders (TMD) are still under investigation. The hypothesis that TMD pain is caused by a generalized sensitization of higher order neurons in the nociceptive pathways combined with a decreased efficacy of endogenous inhibitory systems has recently gained support in the literature. This study was designed to further investigate the somatosensory sensibility within and outside the craniofacial region. Twenty-two patients fulfilled the research diagnostic criteria for TMD for myofascial pain (Dworkin and LeResche, J Craniomandib Disord Facial Oral Pain 6 (1992) 301) and 21 age- and sex-matched subjects served as a control group. The somatosensory sensibility to a deep tonic input was tested by standardized infusions of hypertonic saline into the masseter and anterior tibialis muscle. Furthermore, pressure pain thresholds (PPTs) and heat pain thresholds (HPTs) were assessed with phasic stimuli at the same sites before and following the infusions. Myofascial TMD patients reported infusion of hypertonic saline to be more painful on 10 cm visual analogue scales (peak pain 8.8 ± 0.4 cm) than control subjects (6.8 ± 0.5 cm, t-test: P = 0.003) in the masseter but not in the anterior tibialis (7.4 ± 0.5 vs. 6.6 ± 0.5 cm, P = 0.181). The perceived area of experimental masseter pain measured on drawings was marginally larger in TMD patients (2.6 ± 0.5 arbitrary units (a.u.)) than in control subjects (1.4 ± 0.2 a.u., Mann-Whitney: P = 0.048) but no differences were observed for the anterior tibialis (P = 0.771). The PPTs were lower in the myofascial TMD patients compared to the control group, both in the masseter (analysis of variance (ANOVA): P = 0.002) and in the anterior tibialis (P = 0.005), whereas there were no significant differences in HPT (ANOVAs: P = 0.357, P = 0.101). There were no significant correlations between measures of somatosensory sensibility and measures of clinical pain intensity, pain duration, graded chronic pain scores or somatization or depression scores (Pearson: R < 0.304, P > 0.172). The present study in a well-defined group of myofascial TMD patients found that the responsiveness to both tonic and phasic deep stimuli, but not to phasic superficial inputs at the pain threshold level, in the craniofacial region was higher compared with a control group. These findings suggest that myofascial TMD pain is associated with a facilitation of stimulus-evoked pain primarily, but not exclusively related to the painful region. © 2001 International Association for the Study of Pain.
26.	Sundblad, Gunilla Brun, et al. (författare) Self-rated pain and perceived health in relation to stress and physical activity among school-students : a 3-year follow-up. 2008 Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 136:3, s. 239-49 Tidskriftsartikel (refereegranskat)abstract The aim of this longitudinal study was to assess changes with age regarding prevalence of pain and perceived health in a student population, as well as change over time at grade level. Pain included frequency of headache, abdominal, and musculoskeletal pain and perceived health included problems sleeping and/or if they often felt tired, lonely, and sad. If gender, age (grade level), stress, physically activity were related to pain and health complaints were tested with multivariate logistic regression analysis. The students (n=1908) came from randomly selected schools throughout Sweden and attended grades 3, 6 and 9 (ages 9, 12 and 15 at the onset of the year) in 2001. Three years later, 67% (n=1276) of the same students answered a questionnaire that was constructed for the purpose of the studies. The responses given by the same students showed that girls' complaints of pain and perceived health increased with age and boys decreased. Over half (56%) of the girls and two-thirds (67%) of the boys reported no frequent complaints either year. At grade level most variables were rated the same as three years earlier by the same age group. Stress was significantly related to pain and health complaints for girls and the risk of complaints, as calculated with odds ratio, was most evident for students who were characterized as being physically inactive in 2001 and remained inactive three years later. Jointly, significant predictors, such as stress, being physically inactive, gender and grade level, explained 8-20% of the frequent complaints.
27.	Aarnio, Mikko, et al. (författare) Whiplash injuries associated with experienced pain and disability can be visualized with [11C]-D-deprenyl positron emission tomography and computed tomography 2022 Ingår i: Pain. - : Lippincott Williams & Wilkins. - 0304-3959 .- 1872-6623. ; 163:3, s. 489-495 Tidskriftsartikel (refereegranskat)abstract Knowledge of etiological mechanisms underlying whiplash-associated disorders is incomplete. Localisation and quantification of peripheral musculoskeletal injury and inflammation in whiplash-associated disorders would facilitate diagnosis, strengthen patients' subjective pain reports, and aid clinical decisions, all of which could lead to improved treatment. In this longitudinal observational study, we evaluated combined [11C]-D-deprenyl positron emission tomography and computed tomography after acute whiplash injury and at 6-month follow-up. Sixteen adult patients (mean age 33 years) with whiplash injury grade II were recruited at the emergency department. [11C]-D-deprenyl positron emission tomography and computed tomography, subjective pain levels, self-rated neck disability, and active cervical range of motion were recorded within 7 days after injury and again at 6-month follow-up. Imaging results showed possible tissue injuries after acute whiplash with an altered [11C]-D-deprenyl uptake in the cervical bone structures and facet joints, associated with subjective pain locale and levels, as well as self-rated disability. At follow-up, some patients had recovered and some showed persistent symptoms and reductions in [11C]-D-deprenyl uptake correlated to reductions in pain levels. These findings help identify affected peripheral structures in whiplash injury and strengthen the idea that positron emission tomography and computed tomography detectable organic lesions in peripheral tissue are relevant for the development of persistent pain and disability in whiplash injury.
28.	Ackermann, PW (författare) Katz et al., efficacy and safety of tanezumab in the treatment of chronic low back pain [Pain 2011;152:2248-2258] and Hill, blocking the effects of NGF as a route to safe and effective pain relief - fact or fancy? [Pain 2011;152:2200-2201] 2012 Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 1872-6623 .- 0304-3959. ; 153:5, s. 1128-1129 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
29.	Agalave, Nilesh M., et al. (författare) Sex-dependent role of microglia in disulfide high mobility group box 1 protein-mediated mechanical hypersensitivity 2021 Ingår i: Pain. - : Lippincott Williams & Wilkins. - 0304-3959 .- 1872-6623. ; 162:2, s. 446-458 Tidskriftsartikel (refereegranskat)abstract High mobility group box 1 protein (HMGB1) is increasingly regarded as an important player in the spinal regulation of chronic pain. Although it has been reported that HMGB1 induces spinal glial activation in a Toll-like receptor (TLR)4-dependent fashion, the aspect of sexual dimorphisms has not been thoroughly addressed. Here, we examined whether the action of TLR4-activating, partially reduced disulfide HMGB1 on microglia induces nociceptive behaviors in a sex-dependent manner. We found disulfide HMGB1 to equally increase microglial Iba1 immunoreactivity in lumbar spinal dorsal horn in male and female mice, but evoke higher cytokine and chemokine expression in primary microglial culture derived from males compared to females. Interestingly, TLR4 ablation in myeloid-derived cells, which include microglia, only protected male mice from developing HMGB1-induced mechanical hypersensitivity. Spinal administration of the glial inhibitor, minocycline, with disulfide HMGB1 also prevented pain-like behavior in male mice. To further explore sex difference, we examined the global spinal protein expression using liquid chromatography-mass spectrometry and found several antinociceptive and anti-inflammatory proteins to be upregulated in only male mice subjected to minocycline. One of the proteins elevated, alpha-1-antitrypsin, partially protected males but not females from developing HMGB1-induced pain. Targeting downstream proteins of alpha-1-antitrypsin failed to produce robust sex differences in pain-like behavior, suggesting that several proteins identified by liquid chromatography-mass spectrometry are required to modulate the effects. Taken together, the current study highlights the importance of mapping sex dimorphisms in pain mechanisms and point to processes potentially involved in the spinal antinociceptive effect of microglial inhibition in male mice.
30.	Agalave, Nilesh M, et al. (författare) Spinal HMGB1 induces TLR4-mediated long-lasting hypersensitivity and glial activation and regulates pain-like behavior in experimental arthritis. 2014 Ingår i: Pain. - : Lippincott Williams & Wilkins. - 0304-3959 .- 1872-6623. ; 155:9, s. 1802-1813 Tidskriftsartikel (refereegranskat)abstract Extracellular high mobility group box-1 protein (HMGB1) plays important roles in the pathogenesis of nerve injury- and cancer-induced pain. However, the involvement of spinal HMGB1 in arthritis-induced pain has not been examined previously and is the focus of this study. Immunohistochemistry showed that HMGB1 is expressed in neurons and glial cells in the spinal cord. Subsequent to induction of collagen antibody-induced arthritis (CAIA), Hmgb1 mRNA and extranuclear protein levels were significantly increased in the lumbar spinal cord. Intrathecal (i.t.) injection of a neutralizing anti-HMGB1 monoclonal antibody or recombinant HMGB1 box A peptide (Abox), which each prevent extracellular HMGB1 activities, reversed CAIA-induced mechanical hypersensitivity. This occurred during ongoing joint inflammation as well as during the postinflammatory phase, indicating that spinal HMGB1 has an important function in nociception persisting beyond episodes of joint inflammation. Importantly, only HMGB1 in its partially oxidized isoform (disulfide HMGB1), which activates toll-like receptor 4 (TLR4), but not in its fully reduced or fully oxidized isoforms, evoked mechanical hypersensitivity upon i.t. injection. Interestingly, although both male and female mice developed mechanical hypersensitivity in response to i.t. HMGB1, female mice recovered faster. Furthermore, the pro-nociceptive effect of i.t. injection of HMGB1 persisted in Tlr2- and Rage-, but was absent in Tlr4-deficient mice. The same pattern was observed for HMGB1-induced spinal microglia and astrocyte activation and cytokine induction. These results demonstrate that spinal HMGB1 contributes to nociceptive signal transmission via activation of TLR4 and point to disulfide HMGB1 inhibition as a potential therapeutic strategy in treatment of chronic inflammatory pain.
31.	Ahacic, K, et al. (författare) Prevalence of musculoskeletal pain in the general Swedish population from 1968 to 2002 : Age, period, and cohort patterns 2010 Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 151:1, s. 206-214 Tidskriftsartikel (refereegranskat)abstract We examined age, period, and cohort patterns in musculoskeletalpainprevalence between 1968 and 2002 in the Swedishpopulation. A repeated nationally representative survey allowed cross-sectional comparisons of ages 18–75 (5 waves n ≈ 5000), and ages 77+ at later waves (2 waves n ≈ 500). Cross-sectional 10-year age group differences in 5 waves, time-lag differences between waves (shifts across time) for age groups, and within-cohort differences between waves for 10-year birth cohorts followed over time were analyzed using graphs and ordered logistic regressions. The outcome scale was based on the three items measuring slight or severe pain in back, shoulder, and joints during the past 12 months. Age–period–cohort models showed that painprevalence increased with age – mild or severe at all locations. Adjusted for the age-related increase, the cohorts followed over time did not show significant period change, except for cohorts born during 1940s. Beginning with the 1940s’ cohorts painprevalence increased over the period, and after baseline later cohorts also entered adulthood and the study with a higher painprevalence. The prevalence of pain in the adult population thus increased with the passage through age and time of the 1940s cohorts. While there were no pronounced cohort differences at baseline in 1968, results demonstrated strong age effects in pain. The results indicate that the prevalence of musculoskeletalpain among the oldest age groups may increase in the future, when more baby-boomers are entering their oldest ages.
32.	Ahmed, Aisha S, et al. (författare) Suppression of pain and joint destruction by inhibition of the proteasome system in experimental osteoarthritis 2012 Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 153:1, s. 18-26 Tidskriftsartikel (refereegranskat)abstract Osteoarthritis is a degenerative joint disease with pain and loss of joint function as major pathological features. Recent studies show that proteasome inhibitors reduce pain in various pathological conditions. We evaluated the effects of MG132, a reversible proteasome inhibitor on pain and joint destruction in a rat model of osteoarthritis. Osteoarthritis was induced by intraarticular injection of monosodium iodoacetate into the rat knee. Knee joint stiffness was scored and nociception was evaluated by mechanical pressure applied to the respective hind paw. Knee joint destruction was assessed by radiological and histological analyses. Expression of matrix metalloproteinase-3 (MMP-3) was analyzed by quantitative reverse transcription polymerase chain reaction in the knee articular cartilage. Expression of substance P (SP) and calcitonin gene-related peptide (CGRP) was studied in the dorsal root ganglia (L4–L6) by quantitative reverse transcription polymerase chain reaction and in the knee joints by immunohistochemistry. Our results indicate that daily treatment of osteoarthritic rats with MG132 significantly increases their mobility while the swelling, pain thresholds, and pathological features of the affected joints were reduced. Furthermore, the upregulated expression of MMP-3, SP, and CGRP in the arthritic rats was normalized by MG132 administration. We conclude that the proteasome inhibitor MG132 reduces pain and joint destruction, probably by involving the peripheral nervous system, and that changes in SP and CGRP expression correlate with alterations in behavioural responses. Our findings suggest that nontoxic proteasome inhibitors may represent a novel pharmacotherapy for osteoarthritis.
33.	Aili, Katarina, 1980-, et al. (författare) Long-term trajectories of chronic musculoskeletal pain: a 21-year prospective cohort latent class analysis 2021 Ingår i: Pain. - Philadelphia, PA : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 162:5, s. 1511-1520 Tidskriftsartikel (refereegranskat)abstract Our knowledge of the prevalence, impact, and outcomes of chronic pain in the general population is predominantly based on studies over relatively short periods of time. The aim of this study was to identify and describe trajectories of the chronic pain status over a period of 21 years. Self-reported population data (n = 1858) from 5 timepoints were analyzed. Pain was categorized by: no chronic pain (NCP), chronic regional pain (CRP), and chronic widespread pain (CWP). Latent class growth analysis was performed for identification of trajectories and logistic regression analysis for identification of predictors for pain prognosis. Five trajectories were identified: (1) persistent NCP (57%), (2) migrating from NCP to CRP or CWP (5%), (3) persistent CRP or migration between CRP and NCP (22%), (4) migration from CRP to CWP (10%), and (5) persistent CWP (6%). Age, sleeping problems, poor vitality, and physical function at baseline were associated with pain progression from NCP. Female gender, seeking care for pain, lack of social support, poor physical function, vitality, and mental health predicted poor pain prognosis among those with CRP. In conclusion, chronic pain was common in the population including 6% reporting persistent CWP, although the majority persistently reported NCP. Most people had stable pain status, but some had ongoing change in pain status over time including people who improved from chronic pain. It was possible to identify clinically relevant factors, characterizing trajectories of chronic pain development, that can be useful for identifying individuals at risk and potential targets for intervention.
34.	Alier, Kwai, et al. (författare) Selective stimulation of GalR1 and GalR2 in rat substantia gelatinosa reveals a cellular basis for the anti- and pro-nociceptive actions of galanin 2008 Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 137:1, s. 138-146 Tidskriftsartikel (refereegranskat)abstract Galanin modulates spinal nociceptive processing by interacting with two receptors, GalR1 and GalR2. The underlying neurophysiological mechanisms were examined by whole-cell recording from identified neurons in the substantia gelatinosa of young adult rats. GalR1 was activated with a 'cocktail' containing the GalR1/2 agonist, AR-M 961 (0.5 mu M), in the presence of the GalR2 antagonist, M871 (1.0-2.5 mu M). GalR2 was activated with the selective agonist, AR-M 1896 (0.5-1.0 mu M). Application of the 'GalR1 agonist cocktail' often activated an inwardly-rectifying conductance in delay firing (excitatory) and tonically firing (inhibitory) neurons. This conductance was not activated by AR-M 1896 which instead decreased or increased an outwardly-rectifying conductance at voltages positive to -70 rnV. Despite this variability in its actions on current-voltage relationships, AR-M 1896 very consistently decreased membrane excitability, as measured by cumulative action potential latency in response to a depolarizing current ramp. This strong GalR2-mediated effect was seen in neurons where membrane conductance was decreased, and where membrane excitability might be predicted to increase. GalR2 was also located presynaptically, as AR-M 1896 increased the interevent interval of spontaneous EPSCs in both delay and tonic cells. By contrast, the 'GalR1 agonist cocktail' had little effect on spontaneous EPSCs, suggesting that presynaptic terminals do not express GalR1. These diverse actions of GalR1 and GalR2 activation on both inhibitory and excitatory neurons are discussed in relation to the known spinal antinociceptive and pro-nociceptive actions of galanin, to the possible association of GalR1 with the inhibitory G-protein, G(i/o) and to report that GalR2 activation suppresses Ca(2+) channel currents.
35.	Andrews, NA, et al. (författare) Ensuring transparency and minimization of methodologic bias in preclinical pain research: PPRECISE considerations 2016 Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 1872-6623 .- 0304-3959. ; 157:4, s. 901-909 Tidskriftsartikel (refereegranskat)
36.	Aresh, Bejan, 1984-, et al. (författare) Spinal Cord Interneurons Expressing the Gastrin-Releasing Peptide Receptor Convey Itch Through VGLUT2-Mediated Signaling 2017 Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 158:5, s. 945-961 Tidskriftsartikel (refereegranskat)abstract Itch is a sensation that promotes the desire to scratch, which can be evoked by mechanical and chemical stimuli. In the spinal cord, neurons expressing the gastrin-releasing peptide receptor (GRPR) have been identified as specific mediators of itch. However, our understanding of the GRPR population in the spinal cord, and thus how these neurons exercise their functions, is limited. For this purpose, we constructed a Cre line designed to target the GRPR population of neurons (Grpr-Cre). Our analysis revealed that Grpr-Cre cells in the spinal cord are predominantly excitatory interneurons that are found in the dorsal lamina, especially in laminae II-IV. Application of the specific agonist gastrin-releasing peptide induced spike responses in 43.3% of the patched Grpr-Cre neurons, where the majority of the cells displayed a tonic firing property. Additionally, our analysis showed that the Grpr-Cre population expresses Vglut2 mRNA, and mice ablated of Vglut2 in Grpr-Cre cells (Vglut2-lox; Grpr-Cre mice) displayed less spontaneous itch and attenuated responses to both histaminergic and nonhistaminergic agents. We could also show that application of the itch-inducing peptide, natriuretic polypeptide B, induces calcium influx in a subpopulation of Grpr-Cre neurons. To summarize, our data indicate that the Grpr-Cre spinal cord neural population is composed of interneurons that use VGLUT2-mediated signaling for transmitting chemical and spontaneous itch stimuli to the next, currently unknown, neurons in the labeled line of itch.
37.	Arnison, Tor, 1984-, et al. (författare) Longitudinal, bidirectional relationships of insomnia symptoms and musculoskeletal pain across adolescence : the mediating role of mood 2022 Ingår i: Pain. - : Wolters Kluwer. - 0304-3959 .- 1872-6623. ; 163:2, s. 287-298 Tidskriftsartikel (refereegranskat)abstract Previous studies have established a bidirectional relationship between sleep and pain, and mood has been proposed as a mediator of this relationship. There are only a limited number of longitudinal studies examining the mediational role of mood, and the directionality of effects between sleep, pain and mood is uncertain. Also, and despite the high prevalence of pain and sleep problems during adolescence, these relationships have rarely been examined in a longitudinal sample of adolescents. Here, longitudinal survey data with five yearly measurements was used to examine the bidirectional relationship between insomnia symptoms and pain across adolescence (Mbaseline age = 13.65 years, Nbaseline = 2766). We also explored if depressed mood, positive affect and anxious mood function as mediators in both directions of the sleep-pain relationship. Utilizing latent variables for insomnia, pain and mood at multiple time-points, the data was analyzed with cross-lagged panel models for longitudinal data with structural equation modeling. Current results confirmed a bidirectional relationship between insomnia symptoms and pain, where the effect of insomnia symptoms on pain was stronger than vice versa. Depressed mood and anxious mood mediated the effect of insomnia symptoms on pain, but not the reverse effect of pain on insomnia symptoms. Positive affect did not serve as a mediator in either direction. These findings add novel insights into the temporal directionality of sleep, pain and mood during adolescence, suggesting a temporal path from sleep to pain, via mood, rather than a reciprocal relationship between the constructs.
38.	Baad-Hansen, Lene, et al. (författare) Intraoral somatosensory abnormalities in patients with atypical odontalgia : a controlled multicenter quantitative sensory testing study 2013 Ingår i: Pain. - : Elsevier. - 0304-3959 .- 1872-6623. ; 154:8, s. 1287-1294 Tidskriftsartikel (refereegranskat)abstract Intraoral somatosensory sensitivity in patients with atypical odontalgia (AO) has not been investigated systematically according to the most recent guidelines. The aims of this study were to examine intraoral somatosensory disturbances in AO patients using healthy subjects as reference, and to evaluate the percent agreement between intraoral quantitative sensory testing (QST) and qualitative sensory testing (QualST). Forty-seven AO patients and 69 healthy control subjects were included at Universities of Washington, Malmö, and Aarhus. In AO patients, intraoral somatosensory testing was performed on the painful site, the corresponding contralateral site, and at thenar. In healthy subjects, intraoral somatosensory testing was performed bilaterally on the upper premolar gingiva and at thenar. Thirteen QST and 3 QualST parameters were evaluated at each site, z-scores were computed for AO patients based on the healthy reference material, and LossGain scores were created. Compared with control subjects, 87.3% of AO patients had QST abnormalities. The most frequent somatosensory abnormalities in AO patients were somatosensory gain with regard to painful mechanical and cold stimuli and somatosensory loss with regard to cold detection and mechanical detection. The most frequent LossGain code was L0G2 (no somatosensory loss with gain of mechanical somatosensory function) (31.9% of AO patients). Percent agreement between corresponding QST and QualST measures of thermal and mechanical sensitivity ranged between 55.6% and 70.4% in AO patients and between 71.1% and 92.1% in control subjects. In conclusion, intraoral somatosensory abnormalities were commonly detected in AO patients, and agreement between quantitative and qualitative sensory testing was good to excellent.
39.	Babiloni, A. H., et al. (författare) Towards the endotyping of the sleep-pain interaction: a topical review on multitarget strategies based on phenotypic vulnerabilities and putative pathways 2021 Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 162:5, s. 1281-1288 Tidskriftsartikel (refereegranskat)
40.	Backonja, M, et al. (författare) Value of quantitative sensory testing in neurological and pain disorders: NeuPSIG consensus 2013 Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 1872-6623 .- 0304-3959. ; 154:9, s. 1807-1819 Tidskriftsartikel (refereegranskat)
41.	Baron, R, et al. (författare) Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles 2017 Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 1872-6623 .- 0304-3959. ; 158:2, s. 261-272 Tidskriftsartikel (refereegranskat)
42.	Barr, Travis P., et al. (författare) Sensitization of cutaneous neuronal purinergic receptors contributes to endothelin-1-induced mechanical hypersensitivity 2014 Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 155:6, s. 1091-1101 Tidskriftsartikel (refereegranskat)abstract Endothelin (ET-1), an endogenous peptide with a prominent role in cutaneous pain, causes mechanical hypersensitivity in the rat hind paw, partly through mechanisms involving local release of algogenic molecules in the skin. The present study investigated involvement of cutaneous ATP, which contributes to pain in numerous animal models. Pre-exposure of ND7/104 immortalized sensory neurons to ET-1 (30 nM) for 10 min increased the proportion of cells responding to ATP (2 mu M) with an increase in intracellular calcium, an effect prevented by the ETA receptor-selective antagonist BQ-123. ET-1 (3 nM) pre-exposure also increased the proportion of isolated mouse dorsal root ganglion neurons responding to ATP (0.2-0.4 mu M). Blocking ET-1-evoked increases in intracellular calcium with the IP3 receptor antagonist 2-APB did not inhibit sensitization to ATP, indicating a mechanism independent of ET-1-mediated intracellular calcium increases. ET-1-sensitized ATP calcium responses were largely abolished in the absence of extracellular calcium, implicating ionotropic P2X receptors. Experiments using quantitative polymerase chain reaction and receptor-selective ligands in ND7/104 showed that ET-1-induced sensitization most likely involves the P2X4 receptor subtype. ET-1-sensitized calcium responses to ATP were strongly inhibited by broad-spectrum (TNP-ATP) and P2X4-selective (5-BDBD) antagonists, but not antagonists for other P2X subtypes. TNP-ATP and 5-BDBD also significantly inhibited ET-1-induced mechanical sensitization in the rat hind paw, supporting a role for purinergic receptor sensitization in vivo. These data provide evidence that mechanical hypersensitivity caused by cutaneous ET-1 involves an increase in the neuronal sensitivity to ATP in the skin, possibly due to sensitization of P2X4 receptors.
43.	Bartocci, M, et al. (författare) Pain activates cortical areas in the preterm newborn brain 2006 Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 1872-6623 .- 0304-3959. ; 122:1-2, s. 109-117 Tidskriftsartikel (refereegranskat)
44.	Baumler, P, et al. (författare) Comment on Ernst et al. Acupuncture: does it alleviate pain and are there serious risks? A review of reviews. [Pain 2011;152:755-764] 2011 Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 1872-6623 .- 0304-3959. ; 152:9, s. 2181-2182 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
45.	Bednarska, Olga, 1973-, et al. (författare) Reduced excitatory neurotransmitter levels in anterior insulae are associated with abdominal pain in irritable bowel syndrome 2019 Ingår i: Pain. - : Lippincott Williams & Wilkins. - 0304-3959 .- 1872-6623. ; 160:9, s. 2004-2012 Tidskriftsartikel (refereegranskat)abstract Irritable bowel syndrome (IBS) is a visceral pain condition with psychological comorbidity. Brain imaging studies in IBS demonstratealtered function in anterior insula (aINS), a key hub for integration of interoceptive, affective, and cognitive processes. However,alterations in aINS excitatory and inhibitory neurotransmission as putative biochemical underpinnings of these functional changesremain elusive. Using quantitative magnetic resonance spectroscopy, we compared women with IBS and healthy women (healthycontrols [HC]) with respect to aINS glutamate 1 glutamine (Glx) and g-aminobutyric acid (GABA1) concentrations and addressedpossible associations with symptoms. Thirty-nine women with IBS and 21 HC underwent quantitative magnetic resonancespectroscopy of bilateral aINS to assess Glx and GABA1 concentrations. Questionnaire data from all participants and prospectivesymptom-diary data from patients were obtained for regression analyses of neurotransmitter concentrations with IBS-related andpsychological parameters. Concentrations of Glx were lower in IBS compared with HC (left aINS P , 0.05, right aINS P , 0.001),whereas no group differences were detected for GABA1concentrations. Lower right-lateralized Glx concentrations in patients weresubstantially predicted by longer pain duration, while less frequent use of adaptive pain‐coping predicted lower Glx in left aINS. Ourfindings provide first evidence for reduced excitatory but unaltered inhibitory neurotransmitter levels in aINS in IBS. The results alsoindicate a functional lateralization of aINS with a stronger involvement of the right hemisphere in perception of abdominal pain and ofthe left aINS in cognitive pain regulation. Our findings suggest that glutaminergic deficiency may play a role in pain processing in IBS.
46.	Bendtsen, Preben, 1956-, et al. (författare) What are the qualities of dilemmas experienced when prescribing opioids in general practice? 1999 Ingår i: Pain. - 0304-3959 .- 1872-6623. ; 82, s. 89-96 Tidskriftsartikel (refereegranskat)
47.	Berglund, Anita, et al. (författare) The influence of prognostic factors on neck pain intensity, disability, anxiety and depression over a 2-year period in subjects with acute whiplash injury 2006 Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 125:3, s. 244-256 Tidskriftsartikel (refereegranskat)abstract The influence of potential prognostic factors (occupant- and crash-related factors, initial neck pain intensity and headache, whiplash injury severity, helplessness, locus of control, socioeconomic status) on neck pain intensity (VAS), disability (DRI), anxiety and depression (HADS) was estimated in a cohort of 3704 subjects with whiplash injury following a motor vehicle crash. Questionnaires were administered (baseline, 1-, 6-, 12-, 24-month follow-ups). VAS was trichotomized; "low" (0-30), "moderate" (31-54), "severe" (55-100). A cumulative logit model with a proportional odds assumption was applied. Results regarding depression differed somewhat from the other outcomes. Overall, initial neck pain intensity was an important prognostic factor, but acted also as an evident effect modifier. Females had slightly increased odds for all outcomes but depression, for which no gender differences were shown. Injury severity was associated with all outcomes, but was most pronounced regarding disability among those who perceived numbness/pain in arms/hands and also had severe initial neck pain (proportional odds ratio [OR] 6.5; 95% confidence interval [CI] 2.5-17.0). Initial headache influenced all outcomes. Income was not related to any of the outcomes, whereas a lower level of education was associated with all outcomes but depression. Locus of control was not a factor of importance. In contrast, helplessness was related to all outcomes, but was most pronounced regarding neck pain intensity and depression for subjects with severe initial neck pain (OR 4.8; 95% CI 2.9-7.8; OR 6.6; 95% CI 2.6-17.0). Associations seem to be established early, and then to be relatively constant over time.
48.	Bergman, Stefan, 1959-, et al. (författare) Health status as measured by SF-36 reflects changes and predicts outcome in chronic musculoskeletal pain: a 3-year follow up study in the general population 2004 Ingår i: Pain. - Philadelphia : Ovid Technologies (Wolters Kluwer Health). - 1872-6623 .- 0304-3959. ; 108:1-2, s. 115-123 Tidskriftsartikel (refereegranskat)abstract The SF-36 is a well-validated health status instrument measuring eight different health concepts. One aim of this study was to compare health status as measured by SF-36 in subjects from the general population with no chronic pain (NCP), chronic regional pain (CRP), and chronic widespread pain (CWP). A second aim was to assess if SF-36 could reflect changes in pain status over time. A third aim was to study if health status at baseline, measured by SF-36, could predict pain status 3 years later. The study was designed as a 3-year follow up with a postal questionnaire, including the SF-36 health survey, to 2357 subjects from the general population aged 20-74 years. The results were controlled for age, sex, co-morbidity, and socio-economic status. At baseline, all eight health concepts of SF-36 discriminated between subgroups with NCP, CRP and CWP. Changes in SF-36 over the 3-year follow up time coincided with improvement or deterioration of pain status. Baseline SF-36 scores predicted pain outcome 3 years later. These results support that both physical and mental aspects of health status as measured by SF-36 are affected by the burden of musculoskeletal pain, are sensitive to changes in pain status, and also predict the further development of pain. (C) 2003 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
49.	Berna, C, et al. (författare) Side effects can enhance treatment response through expectancy effects: an experimental analgesic randomized controlled trial 2017 Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 1872-6623 .- 0304-3959. ; 158:6, s. 1014-1020 Tidskriftsartikel (refereegranskat)
50.	Bernfort, Lars, et al. (författare) Severity of chronic pain in an elderly population in Sweden-impact on costs and quality of life 2015 Ingår i: Pain. - : Elsevier / Lippincott, Williams andamp; Wilkins. - 0304-3959 .- 1872-6623. ; 156:3, s. 521-527 Tidskriftsartikel (refereegranskat)abstract Chronic pain is associated with large societal costs, but few studies have investigated the total costs of chronic pain with respect to elderly subjects. The elderly usually require informal care, care performed by municipalities, and care for chronic diseases, all factors that can result in extensive financial burdens on elderly patients, their families, and the social services provided by the state. This study aims to quantify the societal cost of chronic pain in people of age 65 years and older and to assess the impact of chronic pain on quality of life. This study collected data from 3 registers concerning health care, drugs, and municipal services and from 2 surveys. A postal questionnaire was used to collect data from a stratified sample of the population 65 years and older in southeastern Sweden. The questionnaire addressed pain intensity and quality of life variables (EQ-5D). A second postal questionnaire was used to collect data from relatives of the elderly patients suffering from chronic pain. A total of 66.5% valid responses of the 10,000 subjects was achieved; 76.9% were categorized as having no or mild chronic pain, 18.9% as having moderate chronic pain, and 4.2% as having severe chronic pain. Consumed resources increased with the severity of chronic pain. Clear differences in EQ-5D were found with respect to the severity of pain. This study found an association between resource use and severity of chronic pain in elderly subjects: the more severe the chronic pain, the more extensive (and expensive) the use of resources.

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