| 1. |
- Groen, Solveig Skovlund, et al.
(författare)
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A serological type II collagen neoepitope biomarker reflects cartilage breakdown in patients with osteoarthritis
- 2021
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Ingår i: Osteoarthritis and Cartilage Open. - : Elsevier BV. - 2665-9131. ; 3:4
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: There is an unmet medical need for biomarkers in OA which can be applied in clinical drug development trials. The present study describes the development of a specific and robust assay measuring type II collagen degradation (T2CM) and discusses its potential as a noninvasive translational biomarker. Methods: A type II collagen specific neoepitope (T2CM) was identified by mass spectrometry and monoclonal antibodies were raised towards the epitope, employed in a chemiluminescence immunoassay. T2CM was assessed in bovine cartilage explants with or without MMP-13 inhibitor, and explant supernatants were analyzed by Western blot. T2CM was measured in plasma samples from one study (n = 48 patients) where OA patients were referred to total knee replacement (TKR). Additionally, T2CM was quantified in serum from OA patients receiving salmon calcitonin treatment (sCT) (n = 50) compared to placebo (n = 57). Results: The T2CM assay was technically robust (13/4 % inter/intra-variation) and specific for the type II collagen fragment cleaved by MMP-1 and -13. The MMP-13 inhibitor reduced the T2CM release from bovine cartilage explants receiving catabolic treatment. These results were confirmed by Western blot. In human end-stage OA patients (scheduled for TKR), the T2CM levels were elevated compared to moderate OA (p<0.004). The OA patients receiving sCT had lower levels of T2CM compared to placebo group after 1, 6, and 24 months of treatment (p = 0.0285, p = 0.0484, p = 0.0035). Conclusions: To our knowledge, T2CM is the first technically robust serological biomarker assay which has shown biological relevance in ex vivo models and OA cohorts. This suggests that T2CM may have potential as a translational biomarker for cartilage degradation.
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| 2. |
- Lemming, Dag, 1962-, et al.
(författare)
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Cuff Pressure Pain Detection Is Associated with Both Sex and Physical Activity Level in Nonathletic Healthy Subjects
- 2017
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Ingår i: Pain medicine (Malden, Mass.). - Oxford : Oxford University Press. - 1526-2375 .- 1526-4637. ; 18:8, s. 1573-1581
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. The aim of this study was to evaluate pressure pain sensitivity on leg and arm in 98 healthy persons (50 women) using cuff algometry. Furthermore, associations with sex and physical activity level were investigated.Method. Normal physical activity level was defined as Godin Leisure-Time Exercise Questionnaire (GLTEQ) score ≤ 45 and high activity level as GLTEQ > 45. A pneumatic double-chamber cuff was placed around the arm or leg where a single chamber was inflated. The cuff inflation rate (1 kPa/s) was constant, and pain intensity was registered continuously on a 10 cm electronic visual analogue scale (VAS). The pain detection threshold (PDT) was defined as when the pressure was perceived as painful, and pain tolerance (PTT) was when the subject terminated the cuff inflation. For PTT, the corresponding VAS score was recorded (VAS-PTT). The protocol was repeated with two chambers inflated.Result. Only single cuff results are given. For women compared with men, the PDT was lower when assessed in the arm (P = 0.002), PTTs were lower in the arm and leg (P < 0.001), and the VAS-PTT was higher in the arm and leg (P < 0.033). Highly active participants compared with less active had higher PDT (P = 0.027) in the leg. Women showed facilitated spatial summation (P < 0.014) in the arm and leg and a steeper VAS slope (i.e., the slope of the VAS pressure curve between PDT and PPT) in the arm and leg (P < 0.003).Conclusion. This study indicates that reduced pressure pain sensitivity is associated both with male sex and physical activity level.
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| 3. |
- Lemming, Dag, et al.
(författare)
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Managing chronic whiplash associated pain with a combination of low-dose opioid (remifentanil) and NMDA-antagonist (ketamine)
- 2007
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Ingår i: European Journal of Pain. - : Wiley. - 1090-3801 .- 1532-2149. ; 11:7, s. 719-732
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to investigate the efficacy of a combination of low-dose remifentanil (REMI) and ketamine (KET) compared to the single drugs and placebo (P) on whiplash associated pain (WAD) in a double-blind, randomized, placebo-controlled, cross-over study. Twenty patients with chronic (>1 year) WAD were included. Four different drug combinations were tested in four sessions: placebo/placebo (P/P), placebo/remifentanil (P/REMI), ketamine/placebo (KET/P) and ketamine/remifentanil (KET/REMI). Target concentrations were 1 and 2 ng/ml (stepwise) for remifentanil and 100 ng/ml for ketamine. Habitual pain intensity was assessed on a visual analogue scale (VAS). Experimental pain was assessed with electrical stimulation (single and repeated) of tibialis anterior (TA) muscle, pressure pain algometry applied over infraspinatus (IS) and TA muscles and VAS scores after intramuscular hypertonic saline infusion in TA. KET/REMI significantly reduced habitual pain. KET/REMI infused at low REMI target concentration (1 ng/ml) significantly elevated electrical intramuscular pain thresholds (single and repeated). Pain thresholds to electrical stimulation were similarly increased by both P/REMI and KET/REMI at 2 ng/ml target concentration. Pressure pain thresholds were increased by both KET/REMI and P/REMI. VAS-scores after intramuscular saline were also similarly decreased by both REMI combinations. Seven out of 20 subjects were non-responders (<50% pain relief). No correlation was found between effects on spontaneous pain and experimental pain. KET/REMI showed an analgesic effect on habitual pain. Experimental pain was attenuated by both combinations containing the opioid, however, KET seemed to enhance the effect of REMI on electrical pain thresholds when a low REMI target concentration was used.
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| 4. |
- Lemming, Dag, et al.
(författare)
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Single-point but not tonic cuff pressure pain sensitivity is associated with level of physical fitness : a study of non-athletic healthy subjects
- 2015
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Ingår i: PLOS ONE. - Linköping : Public Library of Science. - 1932-6203. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Exercise is often used for pain rehabilitation but the link between physical activity level and pain sensitivity is still not fully understood. Pressure pain sensitivity to cuff algometry and conditioned pain modulation (CPM) were evaluated in highly active men (n=22), normally active men (n=26), highly active women (n=27) and normally active women (n=23) based on the Godin Leisure-Time Exercise Questionnaire. Cuff pressure pain sensitivity was assessed at the arm and lower leg. The subjects scored the pain intensity on an electronic Visual Analogue Scale (VAS) during ten minutes with 25 kPa constant cuff pressure and two minutes with zero pressure. The maximal VAS score and area under the VAS-curve were extracted. Pressure pain thresholds (PPT) were recorded by manual pressure algometry on the ipsilateral tibialis anterior muscle before, during and after the tonic arm stimulation.Tonic cuff stimulation of the arm and leg resulted in higher VAS peak scores in women compared with men (p<0.04). In all groups the PPTs were reduced during and after the cuff stimulation compared with baseline (p=0.001). PPT were higher in men compared with women (p=0.03) and higher in highly physical active compared with normal active (p=0.048). Besides the well-known gender difference in pressure pain sensitivity this study demonstrates that a high physical fitness degree in non-athletic subjects is associated with increased pressure pain thresholds but does not affect cuff pressure pain sensitivity in healthy people.
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| 5. |
- Lemming, Dag, et al.
(författare)
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The responses to pharmacological challenges and experimental pain in patients with chronic whiplash-associated pain
- 2005
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Ingår i: The Clinical Journal of Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0749-8047 .- 1536-5409. ; 21:5, s. 412-421
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This study evaluates the analgesic responses to intravenous administration of morphine, lidocaine, and ketamine and their relations to duration of chronic pain after whiplash trauma. In addition, experimental muscle pain sensitivity and its correlation to pain duration and pharmacological responses were assessed. Methods: Thirty-three patients with diagnosed whiplash-associated disorder grade II in the chronic stage, according to the Quebec classification, were included. The pharmacological evaluation was performed in a randomized, double-blind, cross-over design and consisted of a 30-minute period of intravenous administration of morphine (0.3 mg/kg), lidocaine (5 mg/kg), ketamine (0.3 mg/kg), or placebo (isotonic saline). Intensity ratings of habitual pain on a visual analogue scale were taken before, during, and after the infusion. The patients were classified as nonresponders, placebo-responders, or responders (minimum 50% decrease of pain intensity) of the drugs. Pressure pain thresholds and intramuscular and cutaneous electrical stimulation pain thresholds were measured. The pain intensity during experimental muscle pain by intramuscular hypertonic saline was also recorded. Experimental pain assessments were performed on the lower legs outside the habitual painful area. Results: Thirty patients completed the study; 2 were placebo responders and 10 were nonresponders. Of 18 responders, there were 15 morphine responders, 11 lidocaine responders, and 14 ketamine responders. In the patients with whiplash-associated disorder duration less than 2 years, 7 responded to morphine, 5 to lidocaine, and 8 to ketamine. In the patients with pain duration longer than 2 years, 8 responded to morphine, 6 to lidocaine, and 6 to ketamine. Thus, no pattern with respect to pain duration was found. Seventeen patients participated in the experimental pain assessment, and no significant differences in the variables of the intramuscular and cutaneous stimulation and intramuscular-induced pain with respect to response to the pharmacological challenges or whiplash-associated disorder duration existed. Discussion: The pharmacological challenges identified subgroups of patients with chronic whiplash-associated disorder that might be considered before instituting therapeutic interventions or research. However, the pattern of responses to the pharmacological challenges did not show any clear relationships with pain duration or the experimental pain tests.
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| 6. |
- Lemming, Dag, et al.
(författare)
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Widespread pain hypersensitivity and facilitated temporal summation of deep tissue pain in whiplash associated disorder : an explorative study of women
- 2012
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Ingår i: Journal of Rehabilitation Medicine. - : Foundation for Rehabilitation Information. - 1650-1977 .- 1651-2081. ; 44:8, s. 648-657
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Widespread deep tissue pain hyperalgesia was evaluated in women with chronic whiplash associated disorder (n=25) and controls (n=10) using computerized cuff pressure algometry and hypertonic saline infusion. Methods: A pneumatic double-chamber cuff was placed around: (i) the arm and (ii) the leg. Cuff inflation rate was constant and the pain intensity was registered continuously on a visual analogue scale (VAS); thresholds of detection and tolerance were extracted. For assessment of spatial summation the protocol was repeated with a single-chamber cuff inflated around the leg. Temporal summation of pain was assessed from the leg with constant cuff pressure stimulation at 2 different pressure intensities for 10 min. Hypertonic saline was infused in the tibialis anterior muscle. Results: Cuff pressure pain thresholds were lower in subjects with whiplash associated disorder compared with controls (pless than0.05). Tonic pressure stimulation evoked higher maximal VAS and larger areas under the VAS curve in subjects with whiplash associated disorder compared with controls (pless than0.05). The pain threshold and tolerance were higher during single cuff than double cuff stimulation. The area under the VAS curve after intramuscular saline infusion was larger in whiplash associated disorder (pless than0.05). Conclusion: The results indicated widespread hyperalgesia in chronic whiplash associated disorder and facilitated temporal summation outside the primary pain area, suggesting involvement of central sensitization.
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| 7. |
- Skogberg, Olle, et al.
(författare)
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Pain Tolerance in Chronic Pain Patients Seems to be More Associated with Physical Activity than with Depression and Anxiety
- 2022
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Ingår i: Journal of Rehabilitation Medicine. - : Foundation for Rehabilitation Information. - 1650-1977 .- 1651-2081. ; 54
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To explore the associations between habitual self-reported physical activity, pain sensitivity and patient-reported outcomes (including pain intensity) in patients with chronic pain. Design: Cross-sectional, experimental study. Subjects: Patients (n = 78), age range 18-65 years, with different chronic pain conditions (> 3 months) were compared with age- and sex-matched healthy controls (n = 98). Methods: Multivariate correlations between selfreported physical activity, pressure pain sensitivity, and patient-reported outcome measures were assessed. Results: Lower perceived health status (p <0.001, Cohens d =2.34), higher levels of depression (p< 0.001, Cohens d = 1.77), and lower pain tolerance threshold (p < 0.001, Cohens d = 1.66) were the most prominent variables discriminating patients from controls. In patients, bivariate and multivariate analyses showed that higher pressure pain tolerance was associated with male sex, lower pain intensity and fewer painful regions, higher self-efficacy and more self-reported physical activity, but not with lower levels of anxiety and depression. Conclusion: Pain tolerance thresholds, as well as degree of depression and perceived health status discriminated between patients and controls, and there was an association between pain tolerance thresholds and level of self-reported physical activity in patients. This study highlights the importance of further research into how increased physical activity may improve pain sensitivity in patients with chronic pain.
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| 8. |
- Arendt Nielsen, Lars, et al.
(författare)
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Pathophysiological mechanisms in chronic musculoskeletal pain (fibromyalgia) : the role of central and peripheral sensitization and pain disinhibition
- 2007
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Ingår i: Baillière's Best Practice & Research. - : Elsevier BV. - 1521-6942 .- 1532-1770. ; 21:3, s. 465-480
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Tidskriftsartikel (refereegranskat)abstract
- Chronic musculoskeletal pain has biological, psychological and social components. This review deals with the biological factors, with emphasis on the fibromyalgia syndrome (FMS). Studies on central sensitization of pain-transmitting neurons, changes in endogenous pain modulation that give rise to pain disinhibition, referred pain, pain-related decrease in muscle strength and endurance, and pain generators in deep tissues are reviewed. In FMS there is strong scientific support for the statement that the biological part of the syndrome is a longstanding or permanent change in the function of the nociceptive nervous system that can be equated with a disease. Further research is necessary in order to determine which methods are best for diagnosis of the pain hypersensitivity in clinical practice. FMS may be the far end of a continuum that starts with chronic localized/regional musculoskeletal pain and ends with widespread chronic disabling pain. © 2007 Elsevier Ltd. All rights reserved.
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| 9. |
- Biurrun Manresa, Jose A., et al.
(författare)
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Dynamic Changes in Nociception and Pain Perception After Spinal Cord Stimulation in Chronic Neuropathic Pain Patients
- 2015
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Ingår i: The Clinical Journal of Pain. - : LIPPINCOTT WILLIAMS and WILKINS. - 0749-8047 .- 1536-5409. ; 31:12, s. 1046-1053
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Patients with an implanted spinal cord stimulation (SCS) system for pain management present an opportunity to study dynamic changes in the pain system in a situation where patients are not stimulated (ie, experiencing severe pain) compared with a situation in which patients have just been stimulated (ie, pain free or greatly reduced pain). The aims of this study were (1) to determine if there are differences in nociceptive withdrawal reflex thresholds (NWR-T) and electrical pain thresholds (EP-T) before and after SCS; and (2) to establish if these differences are related to psychological factors associated with chronic pain. Methods: Seventeen volunteers with chronic neuropathic pain participated in the experiment. Electrical stimuli were applied to assess the NWR-T and the EP-T. In addition, psychological factors (ie, pain characteristics, depression, anxiety, and disability indexes) were also recorded. The NWR-T and EP-T were assessed with the SCS system off (at least 8 h before the experiment), and then reassessed 1 hour after the SCS system was turned on. Results: Ongoing pain intensity ratings decreased (P=0.018), whereas the NWR-T increased (P=0.028) after the SCS was turned on, whereas no significant difference was found for EP-T (P=0.324). Psychological factors were significant predictors for EP-T but not for NWR-T. Discussion: The results of this study suggest that pain relief after SCS is partially mediated by a decrease in the excitability of dorsal horn neurons in the spinal cord.
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| 10. |
- Boudreau, Shellie A., et al.
(författare)
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Features of cortical neuroplasticity associated with multidirectional novel motor skill training: a TMS mapping study
- 2013
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Ingår i: Experimental Brain Research. - : Springer Science and Business Media LLC. - 0014-4819 .- 1432-1106. ; 225:4, s. 513-526
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Tidskriftsartikel (refereegranskat)abstract
- Given the evidence that the primary motor cortex (MI) consists of subpopulations of upper motor neurons tuned to different directional parameters of a motor movement, this study hypothesized that novel motor skill training involving either a bidirectional or more complex multidirectional tongue-typing movement should produce distinct training-related features of tongue MI neuroplasticity in humans. Novel motor skill training consisted of tongue typing using custom-made intra-oral keypads for 30-min over two consecutive days. The bidirectional keypad consisted of three sensors positioned along the upper palatal midline as a 3 x 1 array, whereas the multidirectional keypad consisted of nine sensors arranged as a 3 x 3 array that was centred along the upper palatal midline. Each sensor corresponded to one letter and participants were asked to type sequences of letters by accurately placing the tongue over the correct sensor. Before and after each training session, excitability of the tongue MI was assessed with transcranial magnetic stimulation (TMS)-motor evoked potentials (MEPs) over 13 motor map sites and TMS-MEP stimulus-response curves were constructed for the first dorsal interosseous (FDI, as an internal control). Tongue-typing performance improved within and across training days for both groups; although bidirectional training displayed greater success. Bidirectional and multidirectional training were associated with increases and decreases in a number of cortical motor map sites from where tongue activity could be evoked, however; multidirectional training was associated with a greater number of cortical motor map sites with increased excitability and a shift in the centre of gravity of the motor map. No effects of training were found on the FDI TMS-MEP stimulus-response curves. This study revealed distinct training-related features of tongue MI neuroplasticity and proposes that a greater amount of functionally related neuronal populations may be 'trained' by the inclusion of different and more complex directional parameters within a novel motor task.
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