| 1. |
- Eftekhari, Sajedeh, et al.
(författare)
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Differentiation of Nerve Fibers Storing CGRP and CGRP Receptors in the Peripheral Trigeminovascular System.
- 2013
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Ingår i: Journal of Pain. - : Elsevier BV. - 1526-5900. ; 14:11, s. 1289-1303
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Tidskriftsartikel (refereegranskat)abstract
- Primary headaches such as migraine are postulated to involve the activation of sensory trigeminal pain neurons that innervate intracranial blood vessels and the dura mater. It is suggested that local activation of these sensory nerves may involve dural mast cells as one factor in local inflammation, causing sensitization of meningeal nociceptors. Immunofluorescence was used to study the detailed distribution of calcitonin gene-related peptide (CGRP) and its receptor components calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) in whole-mount rat dura mater and in human dural vessels. The relative distributions of CGRP, CLR, and RAMP1 were evaluated with respect to each other and in relationship to mast cells, myelin, substance P, neuronal nitric oxide synthase, pituitary adenylate cyclase-activating polypeptide, and vasoactive intestinal peptide. CGRP expression was found in thin unmyelinated fibers, whereas CLR and RAMP1 were expressed in thicker myelinated fibers coexpressed with an A-fiber marker. CLR and RAMP1 immunoreactivity colocalized with mast cell tryptase in rodent; however, expression of both receptor components was not observed in human mast cells. Immunoreactive substance P fibers coexpressed CGRP, although neuronal nitric oxide synthase and vasoactive intestinal peptide expression was very limited, and these fibers were distinct from the CGRP-positive fibers. Few pituitary adenylate cyclase-activating polypeptide immunoreactive fibers occurred and some colocalized with CGRP.
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| 2. |
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| 3. |
- Jensen, Karin B, et al.
(författare)
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Segregating the cerebral mechanisms of antidepressants and placebo in fibromyalgia.
- 2014
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Ingår i: Journal of Pain. - : Elsevier BV. - 1526-5900 .- 1528-8447. ; 15:12, s. 1328-37
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Tidskriftsartikel (refereegranskat)abstract
- UNLABELLED: Antidepressant drugs are commonly used to treat fibromyalgia, but there is little knowledge about their mechanisms of action. The aim of this study was to compare the cerebral and behavioral response to positive treatment effects of antidepressants or placebo. Ninety-two fibromyalgia patients participated in a 12-week, double-blind, placebo-controlled clinical trial with milnacipran, a serotonin-norepinephrine reuptake inhibitor. Before and after treatment, measures of cerebral pain processing were obtained using functional magnetic resonance imaging. Also, there were stimulus response assessments of pressure pain, measures of weekly pain, and fibromyalgia impact. Following treatment, milnacipran responders exhibited significantly higher activity in the posterior cingulum compared with placebo responders. The mere exposure to milnacipran did not explain our findings because milnacipran responders exhibited increased activity also in comparison to milnacipran nonresponders. Stimulus response assessments revealed specific antihyperalgesic effects in milnacipran responders, which was also correlated with reduced clinical pain and with increased activation of the posterior cingulum. A short history of pain predicted positive treatment response to milnacipran. We report segregated neural mechanisms for positive responses to treatment with milnacipran and placebo, reflected in the posterior cingulum. The increase of pain-evoked activation in the posterior cingulum may reflect a normalization of altered default mode network processing, an alteration implicated in fibromyalgia pathophysiology.PERSPECTIVE: This study presents neural and psychophysical correlates to positive treatment responses in patients with fibromyalgia, treated with either milnacipran or placebo. The comparison between placebo responders and milnacipran responders may shed light on the specific mechanisms involved in antidepressant treatment of chronic pain.
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| 4. |
- Kankel, Jennifer, et al.
(författare)
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Differential effects of low dose lidocaine on C-fiber classes in humans
- 2012
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Ingår i: Journal of Pain. - : Elsevier BV. - 1526-5900 .- 1528-8447. ; 13:12, s. 1232-1241
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Tidskriftsartikel (refereegranskat)abstract
- The nonselective sodium channel blocker lidocaine is widely used as a local anesthetic but also systemically for treatment of postoperative and neuropathic pain. Voltage-gated sodium channels are crucial for action potential generation and conduction, and their availability controls the amount of activity-dependent conduction velocity slowing. This important axonal property, as assessed by microneurography, is used to differentiate human mechanoinsensitive (silent) nociceptors from the classical polymodal nociceptors. In the current study, microneurography was used to assess axonal properties of the 2 main nociceptor classes in humans, before and after intradermal injection of lidocaine .1% or control saline solution in the receptive field. In mechanosensitive nociceptors, lidocaine reduced baseline conduction velocity and turned activity-dependent slowing into speeding of conduction. In contrast, mechanoinsensitive fibers were not affected in their baseline conduction velocity or their activity-dependent slowing, but probability of conduction block with repetitive stimulation increased. Recovery cycles showed reduced hyperpolarization in all C-fiber classes after lidocaine injections. These results support our hypothesis that sodium channel subtypes are differentially expressed in the 2 nociceptor classes of mechanosensitive C-fibers (CMs) and mechanoinsensitive C-fibers (CMis).Perspective: This study reveals that microneurography can be used to assess pharmacologicaleffects on single C-fibers directly in humans.
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| 5. |
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| 6. |
- Rothaug, J., et al.
(författare)
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Patients' perception of postoperative pain management : Validation of the international pain outcomes (IPO) questionnaire
- 2013
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Ingår i: Journal of Pain. - : Elsevier BV. - 1526-5900 .- 1528-8447. ; 14:11, s. 1361-1370
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Tidskriftsartikel (refereegranskat)abstract
- PAIN OUT is a European Commission-funded project aiming at improving postoperative pain management. It combines a registry that can be useful for quality improvement and research using treatment and patient-reported outcome measures. The core of the project is a patient questionnaire - the International Pain Outcomes questionnaire - that comprises key patient-level outcomes of postoperative pain management, including pain intensity, physical and emotional functional interference, side effects, and perceptions of care. Its psychometric quality after translation and adaptation to European patients is the subject of this validation study. The questionnaire was administered to 9,727 patients in 10 languages in 8 European countries and Israel. Construct validity was assessed using factor analysis. Discriminant validity assessment used Mann-Whitney U tests to detect mean group differences between 2 surgical disciplines. Internal consistency reliability was calculated as Cronbach's alpha. Factor analysis resulted in a 3-factor structure explaining 53.6% of variance. Cronbach's alpha at overall scale level was high (.86), and for the 3 subscales was low, moderate, or high (range,.53-.89). Significant mean group differences between general and orthopedic surgery patients confirmed discriminant validity. The psychometric quality of the International Pain Outcomes questionnaire can be regarded as satisfactory. Perspective The International Pain Outcomes questionnaire provides an instrument for postoperative pain assessment and improvement of quality of care, which demonstrated good psychometric quality when translated into a variety of languages in a large European and Israeli patient population. This measure provides the basis for the first comprehensive postoperative pain registry in Europe and other countries. © 2013 by the American Pain Society.
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| 7. |
- Schrooten, Martien G. S., 1978-, et al.
(författare)
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When pain meets... : pain-related choice behavior and pain perception in different goal conflict situations
- 2014
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Ingår i: Journal of Pain. - : Elsevier BV. - 1526-5900 .- 1528-8447. ; 15:11, s. 1166-1178
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Tidskriftsartikel (refereegranskat)abstract
- Individuals in pain often face the choice between avoiding pain and pursuing other equally valued goals. However, little is known about pain-related choice behavior and pain perception in goal conflict situations. Seventy-eight healthy volunteers performed a computerized task requiring repeated choices between incompatible options, differing in their effect on probability to receive painful stimulation and money. Depending on group assignment, participants chose between increased pain probability versus decreased money probability (avoidance-avoidance conflict situation); decreased pain probability versus increased money probability (approach-approach conflict situation); or decrease versus increase in both probabilities (double approach/avoidance conflict situation). During the choice task, participants rated painfulness, unpleasantness, threat, and fearfulness associated with the painful stimulation and how they felt. Longer choice latency and more choice switching were associated with higher retrospective ratings of conflict and of decision difficulty, and more equal importance placed on pain avoidance and earning money. Groups did not differ in choice behavior, pain stimulus ratings, or affect. Across groups, longer choice latencies were nonsignificantly associated with higher pain, unpleasantness, threat, and fearfulness. In the avoidance-avoidance group, more choice switching was associated with higher pain-related threat and fearfulness, and with more negative affect. These results of this study suggest that associations between choice behaviors, pain perception, and affect depend on conflict situation.Perspective: We present a first experimental demonstration of the relationship between pain-related choice behaviors, pain, and affect in different goal conflict situations. This experimental approach allows us to examine these relationships in a controlled fashion. Better understanding of pain-related goal conflicts and their resolution may lead to more effective pain treatment.
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| 8. |
- Stening, Kent, et al.
(författare)
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Influence of estrogen levels on thermal perception, pain thresholds and pain tolerance : Studies on women undergoing in vitro fertilization
- 2012
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Ingår i: Journal of Pain. - : Elsevier BV. - 1526-5900 .- 1528-8447. ; 13:5, s. 459-466
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Tidskriftsartikel (refereegranskat)abstract
- We examined the relationship between estrogen and pain in women undergoing in vitro fertilization (IVF). Quantitative sensory tests (QST) were performed twice during the IVF-regimen: once during hormonal down-regulation and once during hormonal upregulation. A group of healthy men and a group of women using monophasic contraceptives were also examined, to control for session-to-session effects. Among the women undergoing IVF, serum 17β-estradiol levels differed strongly between treatments as expected, and increased from 65.7 (SD = 26) pmol/l during the downregulation phase, to 5188 (SD = 2524) pmol/l during the up-regulation phase. Significant outcomes in the QST were only seen for temperature perception thresholds (1.7°C vs. 2.2°C; P = 0.003) and cold pain threshold (11.5°C vs. 14.5°C; P = 0.04). A similar change in cold pain threshold was also seen in the two control groups, however, and statistical analysis suggested that this change was due to a session-to-session effect rather than being the result of hormonal modulation. Heat pain thresholds, heat tolerance, pressure pain thresholds, and the cold pressor test showed no significant differences between sessions. These data demonstrate that pain perception and pain thresholds in healthy women show little, if any, changes even with major variations in serum estradiol levels.
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