Pain
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The pharmacological inhibition of anandamide (AEA) hydrolysis by fatty acid amide hydrolase (FAAH) attenuates pain in animal models of osteoarthritis (OA) but has failed in clinical trials. This may have occurred because AEA also activates transient receptor potential vanilloid type 1 (TRPV1), which contributes to pain development. Therefore, we investigated the effectiveness of the dual FAAH-TRPV1 blocker OMDM-198 in an MIA-model of osteoarthritic pain. ⋯ OMDM-198 showed antihyperalgesic effects in the OA model, which were comparable with those of a selective TRPV1 antagonist, SB-366,791, and a selective FAAH inhibitor, URB-597. The effect of OMDM-198 was attenuated by the CB1 receptor antagonist, AM-251, and by the nonpungent TRPV1 agonist, olvanil, suggesting its action as an "indirect" CB1 agonist and TRPV1 antagonist. These results suggest an innovative strategy for the treatment of OA, which may yield more satisfactory results than those obtained so far with selective FAAH inhibitors in human OA.
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Topical high-concentration L-menthol is the only established human experimental pain model to study mechanisms underlying cold hyperalgesia. We aimed at investigating the combinatorial effect of cold stimuli and topical L-menthol on cold pain and secondary mechanical hyperalgesia. Analogue to the heat-capsaicin model on skin sensitization, we proposed that cold/menthol enhances or prolong L-menthol-evoked sensitization. ⋯ Skin blood flow increased after L-menthol (P < 0.001) and stayed stable after cold cycles. Repeated application of cold on skin treated by L-menthol facilitated and prolonged L-menthol-induced cold pain and hyperalgesia. This model may prove beneficial for testing analgesic compounds when a sufficient duration of time is needed to see drug effects on CPT or mechanical hypersensitivity.
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The primary objective of this study was to assess the impact of pediatric pain-related conditions on health care expenditures. We analyzed data from a nationally representative sample of 6- to 17-year-old children captured in the 2007 National Health Interview Survey and 2008 Medical Expenditure Panel Survey. Health care expenditures of children with pain-related conditions were compared with those of children without pain-related conditions. ⋯ The incremental health care expenditures associated with pediatric pain-related conditions were similar to those of attention deficit and hyperactivity disorder ($9.23 billion; 95% CI, $1.89-$18.1 billion), but more than those associated with asthma ($5.35 billion; 95% CI, $0-$12.3 billion) and obesity ($0.73 billion; 95% CI, $6.28-$8.81 billion). Health care expenditures for pediatric pain-related conditions exert a considerable economic burden on society. Efforts to prevent and treat pediatric pain-related conditions are urgently needed.
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Although emotion regulation modulates the pain experience, inconsistencies have been identified regarding the impact of specific regulation strategies on pain. Our goal was to examine the effects of emotion suppression and cognitive reappraisal on automatic (ie, nonverbal) and cognitively mediated (ie, verbal) pain expressions. Nonclinical participants were randomized into either a suppression (n = 58), reappraisal (n = 51), or monitoring control (n = 42) condition. ⋯ Reappraisal and suppression induction led to reductions in nonverbal and verbal indices of pain. Moreover, self-reported tendencies to use suppression and reappraisal (as measured by the Emotion Regulation Questionnaire) did not interact with experimental condition in the determination of participants' responses. Results suggest that consciously applying emotion regulation strategies during a painful task can moderate both cognitively mediated (e.g., verbal) and automatic (e.g., facial activity) expressions of pain.
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Small-fiber neuropathy (SFN) is hallmarked by degeneration of small unmyelinated peripheral nerve fibers in the skin. Traditionally, it has been considered as a pure disorder of the peripheral nervous system. Nevertheless, previous work found that dysfunction of skin nerves led to abnormal recruitment of pain-related regions, suggesting that the brain may be affected in SFN. ⋯ Moreover, the degree of reduction in functional connectivity for the ACC to the amygdala and the precuneus was linearly correlated with the severity of intraepidermal nerve fiber depletion. Our findings suggest that SFN is not a pure peripheral nervous system disorder. The pain-related brain networks tend to break into functionally independent components, with severity linked to the degree of skin nerve degeneration.