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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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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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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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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Randomized Controlled Trial Comparative Study
Adrenergic dysregulation and pain with and without acute beta-blockade in women with fibromyalgia and temporomandibular disorder.
In patients with fibromyalgia syndrome (FMS) and temporomandibular disorder (TMD), stress and pain may chronically enhance sympathetic activity, altering cardiovascular responses and worsening pain. This study examined cardiovascular, epinephrine (EPI), norepinephrine (NE), cortisol and clinical pain responses in 54 female patients with these disorders and 34 controls. In a subsample of 10 FMS, 10 TMD patients and 16 controls, using a counterbalanced, double-blind, crossover design, the same responses were assessed after intravenous administration of low dose propranolol vs placebo. Testing included baseline, postural, speech and ischemic pain stressors. FMS patients showed lesser heart rate (HR) increases to posture challenge but greater blood pressure (BP) increases to postural and speech tasks than controls, as well as higher overall BP and greater total vascular resistance (TVR) than TMDs or controls. TMDs showed higher overall cardiac output and lower TVR than controls. Both FMS and TMD groups showed lower baseline NE than controls, and TMDs showed lower overall EPI and NE levels. Group differences in HR, EPI and NE were abolished after propranolol although BP, CO and TVR differences persisted. In both FMS and TMD, the number of painful body sites and ratings of total clinical pain obtained 4 times during each session were significantly lower after beta-blockade vs placebo. ⋯ These findings support the hypothesis that both FMS and TMD may frequently involve dysregulation of beta-adrenergic activity that contributes to altered cardiovascular and catecholamine responses and to severity of clinical pain. Acute treatment with low-dose propranolol led to short-term improvement in all these domains.