The journal of pain : official journal of the American Pain Society
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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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Recent evidence points to an association between experimental pain measures obtained preoperatively and acute postoperative pain (POP). We hypothesized that pain temporal summation (TS) might be an additional predictor for POP insofar as it represents the neuroplastic changes that occur in the central nervous system following surgery. Therefore, a wide range of psychophysical tests (TS to heat and mechanical repetitive stimuli, pain threshold, and suprathreshold pain estimation) and personality tests (pain catastrophizing and anxiety levels) were administered prior to thoracotomy in 84 patients. POP ratings were evaluated on the 2nd and 5th days after surgery at rest (spontaneous pain) and in response to activity (provoked pain). Linear regression models revealed that among all assessed variables, enhanced TS and higher pain scores for mechanical stimulation were significantly associated with greater provoked POP intensity (overall r2 = 0.225, P = .008). Patients who did not demonstrate TS to both modalities reported lower scores of provoked POP as compared with patients who demonstrated TS in response to at least 1 modality (F = 4.59 P = .013). Despite the moderate association between pain catastrophizing and rest POP, none of the variables predicted the spontaneous POP intensity. These findings suggest that individual susceptibility toward a greater summation response may characterize patients who are potentially vulnerable to augmented POP. ⋯ This study proposed the role of pain temporal summation assessed preoperatively as a significant psychophysical predictor for acute postoperative pain intensity. The individual profile of enhanced pain summation is associated with the greater likelihood of higher postoperative pain scores.
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Neuropathic pain (NP) is a difficult issue, particularly in cancer which is a dynamic condition where multiple pain etiologies are concomitantly present. Cancer pain is often labeled as mixed mechanism pain and is not easily classified as exclusively nociceptive or NP. The aim of this study was to explore the value of evaluation tools such as Neuropathic Pain Questionnaire (NPQ), complete and short form (NPQ-SF), Leeds Assessment of Neuropathic Signs and Symptoms (LANSS) and Neuropathic Pain Symptom Inventory (NPSI). The secondary outcome was to evaluate the response to opioid titration, according to the hierarchical classification of definite, possible and unlikely NP. A consecutive sample of patients referred for treatment of cancer-related pain were eligible for participation in the study. The inclusion criterion was uncontrolled cancer pain requiring adjustment of opioid therapy. Patients were clinically classified into tertiles based according to graded evidence of nervous system lesion: definite NP, possible NP, or unlikely NP. Pain and symptoms intensities were measured before (T0) and at the end of opioid titration (T1). Patients were titrated with escalating doses of opioids, supported by symptomatic drugs, changing the route of administration, or by opioid switching according to the clinical response. At T1 the opioid response was clinically graded from 1 to 4. Opioid escalation index was calculated. A single independent investigator, blinded to the clinical assessment and treatment, collected data from NPQ, NPQ-SF, LANSS Pain Scale, and NPSI. One hundred and sixty-seven patients concluded the study. Sixty, thirty-six, and seventy-one patients were clinically assessed as having definite NP, possible NP, or unlikely NP, respectively. A relationship between the values of the assessment tools and clinician rating was found. Patients with the highest values of assessment tools were also more likely to be clinically labeled as definite NP, although sensibility and specificity were low. Patients with a clinical diagnosis of definite NP, possible NP, or unlikely NP showed significant differences in opioid response (P < .0005). Patients with "unlikely NP" had a lower pain intensity at T1 (P < .05), and patients with "definite NP" required more intensive treatment. Patients requiring more aggressive treatment showed significantly higher values of Opioid Escalation Index (OEI)mg. ⋯ Screening tools may provide a basis to suggest a common language in cancer pain syndromes. A hierarchical grouping seems to be more flexible and fits cancer patient characteristics. This study also confirms that opioids are clinically effective in "definite NP" conditions although a more aggressive treatment requiring careful utilization of opioids and symptomatic drugs is strictly necessary.
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The purpose of this study was to investigate the prevalence and demographic risk factors of chronic pain and its comorbidity with depression. Computer-assisted telephone interviewing was utilized to obtain a representative community sample in the state of Michigan (n = 1,179). The prevalence of chronic pain due to any cause was 21.9%. Approximately 35% of participants with chronic pain also had comorbid depression (7.7% of the entire sample). Depression was not associated with pain types or sites. A multinomial-regression analysis revealed several demographic correlates of chronic pain and depression. Participants with chronic pain or comorbid pain and depression were more likely to be older, female, employed less than full-time, and have less education than persons without either condition. Logistic regression analyses showed that younger participants were more likely to have comorbid pain and depression than chronic pain only. A similar but marginally significant effect was found for African American participants. Compared to the depression-only group, those in the comorbid group were more likely to be women and middle-aged. These findings provide additional evidence on the prevalence of comorbid pain and depression in the community and suggest that certain demographic groups with chronic pain may especially benefit from depression screenings. ⋯ This article reports on the prevalence of chronic pain and co-occurring depression in a representative community sample. The high prevalence rates of pain and comorbid depression point to the clinical importance of assessing depression in chronic pain samples.
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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.