Pain
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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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TRPV1 is a nociceptive ion channel activated by polymodal stimuli such as capsaicin, proton, and noxious heat. Multiple inflammatory mediators activate protein kinases, especially protein kinase C (PKC), which phosphorylates TRPV1. Emerging evidence suggests that phosphorylation of TRPV1 constitutes specific signals underpinning pathological nociception. ⋯ Moreover, bradykinin-induced hypersensitivity to capsaicin was largely attenuated by the S800A mutation. These results suggest that mechanisms of PKC-induced hypersensitivity of TRPV1 are modality specific and that S800 is a polymodal sensitization site integrating multiple inflammatory signals in nociceptors. Our data provide a rationale for a novel approach targeting TRPV1 S800 for antihyperalgesia.
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Chronic dry eye disease (DE) is associated with an unstable tear film and symptoms of ocular discomfort. The characteristics of symptoms suggest a key role for central neural processing; however, little is known about central neuroplasticity and DE. We used a model for tear deficient DE and assessed effects on eye blink behavior, orbicularis oculi muscle activity (OOemg), and trigeminal brainstem neural activity in male rats. ⋯ Synaptic blockade at the Vi/Vc transition or the Vc/C1 region greatly reduced hypertonic saline-evoked OOemg activity in DE and sham rats. These results indicated that persistent tear deficiency caused sensitization of ocular-responsive neurons at multiple regions of the caudal trigeminal brainstem and enhanced OOemg activity. Central sensitization of ocular-related brainstem circuits is a significant factor in DE and likely contributes to the apparent weak correlation between peripheral signs of tear dysfunction and symptoms of irritation.