Pain
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We evaluated the role of sigma(1) receptors on capsaicin-induced mechanical hypersensitivity and on nociceptive pain induced by punctate mechanical stimuli, using wild-type and sigma(1) receptor knockout (sigma(1)-KO) mice and selective sigma(1) receptor-acting drugs. Mutation in sigma(1)-KO mice was confirmed by PCR analysis of genomic DNA and, at the protein level, by [(3)H](+)-pentazocine binding assays. Both wild-type and sigma(1)-KO mice not treated with capsaicin showed similar responses to different intensities of mechanical stimuli (0.05-8 g force), ranging from innocuous to noxious, applied to the hind paw. ⋯ The effects of the sigma(1) antagonists were reversed by the sigma(1) agonist PRE-084 (32 mg/kg, s.c.). None of the drugs tested modified the responses induced by a painful mechanical punctate stimulus (4 g force) in nonsensitized animals. These results suggest that sigma(1) receptors are essential for capsaicin-induced mechanical hypersensitivity, but are not involved in mechanical nociceptive pain.
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Randomized Controlled Trial Comparative Study
Efficacy and safety of topical diclofenac containing dimethyl sulfoxide (DMSO) compared with those of topical placebo, DMSO vehicle and oral diclofenac for knee osteoarthritis.
While topical non-steroidal anti-inflammatory drugs are considered safe, their long-term efficacy for osteoarthritis has been suspect. We conducted a 12-week, double-blind, double-dummy, randomized controlled trial of topical diclofenac (TDiclo) in a vehicle solution containing dimethyl sulfoxide (DMSO) in 775 subjects with radiologically confirmed, symptomatic primary osteoarthritis of the knee. This 5-arm study compared TDiclo with a placebo solution, the DMSO vehicle, oral diclofenac (ODiclo) and the combination of TDiclo+ODiclo for relieving the signs and symptoms of knee osteoarthritis. ⋯ Addition of TDiclo to ODiclo did not increase the incidence of systemic adverse events. TDiclo in DMSO vehicle is an effective treatment option for knee osteoarthritis with efficacy similar to, but tolerability better than ODiclo. DMSO vehicle was no more efficacious than placebo.
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Individuals with "insecure" adult attachment styles have been shown to experience more pain than people with secure attachment, though results of previous studies have been inconsistent. We performed a cross-sectional study on a large population-based sample to investigate whether, compared to pain free individuals, subjects with chronic widespread pain were more likely to report insecure adult attachment style. Subjects in a population-based cross-sectional study completed a self-rated assessment of adult attachment style. ⋯ Subjects with CWP were more likely to report a preoccupied (RRR 2.6; 95%CI 1.8-3.7), dismissing (RRR 1.9; 95%CI 1.2-3.1) or fearful attachment style (RRR 1.4; 95%CI 1.1-1.8) than those free of pain. Among CWP subjects, insecure attachment style was associated with number of pain sites (Dismissing: RRR 2.8; 95%CI 1.2-2.3, Preoccupied: RRR=1.8, 95%CI 0.98-3.5) and degree of pain-related disability (Preoccupied: RRR=2.1, 95%CI 1.0-4.1), but not pain intensity. These findings suggest that treatment strategies based on knowledge of attachment style, possibly using support and education, may alleviate distress and disability in people at risk of, or affected by, chronic widespread pain.
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Controlled Clinical Trial
Moderation and mediation in the psychological and drug treatment of chronic tension-type headache: the role of disorder severity and psychiatric comorbidity.
We evaluated two putative moderators of treatment outcome as well as the role of Headache Management Self-Efficacy (HMSE) in mediating treatment outcomes in the drug and non-drug treatment of chronic tension-type headache (CTTH). Subjects were 169 participants (M=38 yrs.; 77% female; M headache days/mo.=22) who received one of four treatments in the treatment of CTTH trial (JAMA, 2001; 285: 2208-15): tricyclic antidepressant medication, placebo, (cognitive-behavioral) stress-management therapy plus placebo, and stress-management therapy plus antidepressant medication. Severity of CTTH disorder and the presence of a psychiatric (mood or anxiety) disorder were found to moderate outcomes obtained with the three active treatments and with placebo, as well as to moderate the role of HMSE in mediating improvements. ⋯ HMSE mediated treatment outcomes in the two stress-management conditions, but the pattern of HMSE mediation was complex, varying with the treatment condition, the outcome measure, and the moderator variable. Irrespective of the severity of the CTTH disorder HMSE fully mediated observed improvements in headache activity in the two stress-management conditions. However, for patients with a mood or anxiety disorder HMSE only partially mediated improvements in headache disability, suggesting an additional therapeutic mechanism is required to explain observed improvements in headache disability in the two stress-management conditions.
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Complex regional pain syndrome, which is characterised by pain and trophic disturbances, develops frequently after peripheral limb trauma. There is an increasing evidence of an involvement of the immune system in CRPS, and recently we showed that CRPS patients have autoantibodies against nervous system structures. Therefore we tested the sera of CRPS patients, neuropathy patients and healthy volunteers for surface-binding autoantibodies to primary cultures of autonomic neurons and differentiated neuroblastoma cell lines using flow cytometry. ⋯ Our data show that about 30-40% of CRPS patients have surface-binding autoantibodies against an inducible autonomic nervous system autoantigen. These data support an autoimmune hypothesis in CRPS patients. Further studies must elucidate origin and function of these autoantibodies in CRPS.