The journal of pain : official journal of the American Pain Society
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Quantification of the human painful sensory experience is an essential step in the translation of knowledge from animal nociception to human pain. Translational models for assessment of pain are very important, as such models can be used in: 1) basic mechanistic studies in healthy volunteers; 2) clinical studies for diagnostic and monitoring purposes; 3) pharmacological studies to evaluate analgesic efficacy of new and existing compounds. Quantitative pain assessment, or quantitative sensory testing (QST), provides psychophysical methods that systematically document alterations and reorganization in nervous system function and, in particular, the nociceptive system. QST is defined as the determination of thresholds or stimulus response curves for sensory processing under normal and pathophysiological conditions. The modern concept of advanced QST for experimental pain assessment is a multimodality, multitissue approach where different pain modalities (thermal, mechanical, electrical, and chemical) are applied to different tissues (skin, muscles, and viscera) and the responses are assessed by psychophysical methods (thresholds and stimulus-response functions). Many new and advanced technologies have been developed to help relieve evoked, standardized, and painful reactions. Assessing pain has become a question of solving a multi-input, multi-output problem, with the solution providing the possibility of teasing out which pain pathways and mechanisms are involved, impaired, or affected. ⋯ Many methodologies have been developed for quantitative assessment of pain perception and involved mechanisms. This paper describes the background for the different methods, the use in basic pain experiments on healthy volunteers, how they can be applied in drug profiling, and the applications in clinical practice.
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Randomized Controlled Trial Multicenter Study
A randomized, double-blind, placebo-controlled trial of a selective COX-2 inhibitor, GW406381, in patients with postherpetic neuralgia.
In this randomized, double-blind, placebo-controlled study, we evaluated the efficacy and safety of GW406381, an investigational selective cyclooxygenase (COX)-2 inhibitor with both peripheral and central actions, in 209 patients with postherpetic neuralgia (PHN). Patients were randomly assigned to GW406381 25 mg or 50 mg or placebo treatments for 3 weeks. The primary efficacy outcome measure was the change in average daily pain intensity score from baseline to the last week of treatment. Both doses of GW406381 produced greater reduction in pain score than placebo, but the treatment difference did not reach statistical significance. It was possible that the 3-week duration was too short, as there was a tendency for increasing separation from placebo over time that did not appear to reach maximum effect by the end of the study for either GW406381 treatment group. Overall, GW406381 was well tolerated in this elderly population. ⋯ To our knowledge, this is the first report of a randomized, controlled clinical trial of a selective or nonselective COX inhibitor in neuropathic pain. The results of this study were inconclusive regarding the clinical relevance of the role of COX-2 in modulation of the symptoms of PHN.
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Fibromyalgia (FM) has been associated with alterations in brain morphometry and abnormal dopaminergic neurotransmission. Evidence from preclinical models has demonstrated that dopamine plays a role in promoting neuronal integrity. We therefore sought to confirm previous findings of reduced gray matter density in subjects with FM and to determine whether variations in dopamine metabolism might affect gray matter density. Voxel-based morphometry was used to evaluate anatomical magnetic resonance imaging data from 30 female FM subjects in comparison with 20 age- and gender-matched healthy control subjects. In addition, data from a subset of subjects from both groups who had previously participated in our positron emission tomography study using radiolabeled DOPA (n = 14; 6 FM subjects and 8 control subjects) was used to determine whether correlation might exist between gray matter density and dopamine metabolism. We found a significant reduction in gray matter density within the bilateral parahippocampal gyri, right posterior cingulate cortex, and left anterior cingulate cortex. In addition, a positive correlation was demonstrated between an index of dopamine metabolism from the ventral tegmental area wherein cell bodies of corticolimbic projection neurons originate and gray matter density, specifically in the bilateral parahippocampal gyri and left pregenual cortex. The current results confirm our previous findings that FM is associated with altered brain morphometry. Alterations in dopamine metabolism might contribute to the associated changes in gray matter density. ⋯ Fibromyalgia is associated with reductions in gray matter density within brain regions ostensibly involved in phenomena related to the disorder, including enhanced pain perception, cognitive dysfunction, and abnormal stress reactivity. Given mounting evidence of abnormal dopaminergic neurotransmission associated with the disorder, the strong correlation between dopamine metabolism and gray matter density provides insight as to the pathophysiology that might contribute to these changes.
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We evaluated the effect of infiltration of dilute solutions of capsaicin, administered before plantar incision, on 3 pain-related behaviors: guarding pain, heat-withdrawal latency, and mechanical-withdrawal threshold. Perineural application of capsaicin was also studied and the appearance of the wound was also evaluated. Dilute solutions of capsaicin .025% and .10% were infiltrated in the plantar region 1 day before incision. In another group of rats, perineural capsaicin (1%) was applied to the nerves innervating the plantar aspect of the rat hindpaw. Rats were then tested for pain-related behaviors before and after plantar incision and then daily thereafter. Wound appearance was graded and histopathology was evaluated. Infiltration with capsaicin reduced guarding pain and heat hyperalgesia after plantar incision; there were minimal effects on mechanical responses. Perineural-capsaicin application produced a similar result. Both capsaicin infiltration and perineural-capsaicin application impaired wound apposition. Histologic evaluation also confirmed impaired wound apposition after capsaicin infiltration. In conclusion, dilute solutions of capsaicin have differential effects on pain-related behaviors after plantar incision. Based on the antinociception produced by capsaicin both via infiltration and perineural injection, the effect on wound appearance was likely related to its inhibitory effects on pain behaviors and was not necessarily a local effect of the drug. ⋯ This study demonstrated that capsaicin infiltration before plantar incision produced an analgesic effect that depended upon the stimulus modality tested. When evaluating novel treatments for postoperative pain, studies using a single stimulus modality may overlook an analgesic effect by not examining a variety of stimuli.
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Although sex differences have been investigated in chronic pain populations, little is known about sex differences in the pain experience of paediatric oncology patients and also whether their parents rate the pain experience differently for boys and girls. The aim of the present study was to determine if (1) boys and girls with cancer differ in current perception and past recollection of cancer-related pain and (2) if adolescents' and parents' pain ratings differ in relation to the sex of the adolescent. One hundred twelve adolescents with malignant diagnoses (12 to 18 years) and their parents participated in the study. Girls reported higher pain intensity within the last 7 days and 4 weeks despite similar diagnosis, physical status, duration of diagnoses, and main pain causes. When asked for pain intensity that dated back in time, parent and adolescent ratings diverged, with a trend for parents to reporting higher pain intensity in boys and lower pain intensity in girls, particularly for pain in the preceding 7 days. The present study provides preliminary evidence for sex differences in the recalled pain experience of adolescents with malignant diagnoses. Although boys and girls experience present pain similarly and hence should be treated similarly, girls recall higher pain intensity than boys. Future studies should address whether negative memories in girls play a significant role and may have an impact on girls' well-being and pain-related distress. Additionally, psychosocial factors such as gender role expectations may need to be investigated. Parental variables and their impact on parents' pain ratings, especially for ratings of precedent pain, warrants further investigation. ⋯ Girls with malignant diagnoses differ from boys in their recalled pain intensity ratings, with girls reporting higher pain intensity. Additional pain management strategies referring to the memory of pain may need to be implemented.