Pain
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Significant age- and experience-dependent remodelling of spinal and supraspinal neural networks occur, resulting in altered pain responses in early life. In adults, endogenous opioid peptide and endocannabinoid (ECs) pain control systems exist which modify pain responses, but the role they play in acute responses to pain and postnatal neurodevelopment is unknown. Here, we have studied the changing role of the ECs in the brainstem nuclei essential for the control of nociception from birth to adulthood in both rats and humans. ⋯ The expression patterns and levels of ECs enzymes and receptors were assessed using quantitative PCR and immunohistochemistry. In human brainstem, we show age-related alterations in the expression of key enzymes and receptors involved in ECs function using PCR and in situ hybridisation. These data reveal that significant changes on ECs that to this point have been unknown and which shed new light into the complex neurochemical changes that permit normal, mature responses to pain.
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More than half of individuals experiencing major thermal burn injury (MThBI) receive an autologous skin graft (autograft), in which skin is removed from a healthy "donor" site and transplanted to the burn site. Persistent pain and itch at the graft site are major causes of suffering and disability in MThBI survivors. African Americans have a higher risk of MThBI, and in other clinical settings African Americans experience a greater burden of pain and itch relative to European Americans. ⋯ In adjusted linear mixed models, African Americans experienced a slower rate of pain resolution in the acute phase of recovery (β = -0.05 vs -0.08 NRS points per day, P < 0.001), which resulted in a higher pain severity in the persistent phase of recovery (NRS mean difference = 1.21, 95% confidence interval [0.12-2.29]), although not statistically significant after correction for multiple comparisons. African Americans also experience greater itch severity in 6 weeks to 12 months after burn injury compared with European Americans (NRS mean difference = 1.86 [0.80-2.93]), which results from a faster rate of itch development in African Americans in the acute recovery phase after burn injury. Future studies may improve outcomes in African Americans and lead to new pathogenic insights that benefit all burn injury survivors.
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Primary dysmenorrhea (PD), or painful menstruation in the absence of identified uterine pathology, affects 5 to 9 in every 10 reproductive-aged women. Despite its high prevalence, just a few studies with very small patient numbers have focused on health-related quality of life impairment in PD. We aimed to assess health-related quality of life values for a severe and a mild hypothetical PD health state using 10-year time trade-off and willingness-to-pay methods. ⋯ Compared with the non-PD group, women with PD valued both health states worse according to willingness to pay (P < 0.05) but similar in the time trade-off. It seems that PD substantially contributes to the quality-adjusted life year loss in this age group, which is comparable with losses from chronic diseases such as type 1 diabetes, asthma, atopic eczema, or chronic migraine. Our findings provide a useful input to cost-effectiveness and cost-benefit analyses of PD treatments.
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The purinergic P2X2 receptor (P2X2R) is an adenosine triphosphate-gated ion channel widely expressed in the nervous system. Here, we identified a putative cyclin-dependent kinase 5 (Cdk5) phosphorylation site in the full-size variant P2X2aR (TPKH), which is absent in the splice variant P2X2bR. We therefore investigated the effects of Cdk5 and its neuronal activator, p35, on P2X2aR function. ⋯ Moreover, co-immunoprecipitation experiments showed an interaction between Cdk5 and P2X2R in mouse trigeminal ganglia. Finally, endogenous P2X2aR-mediated currents in PC12 cells and P2X2/3R mediated increases of intracellular Ca in trigeminal neurons were Cdk5 dependent, since inhibition with roscovitine accelerated the desensitization kinetics of these responses. These results indicate that the P2X2aR is a novel target for Cdk5-mediated phosphorylation, which might play important physiological roles including pain signaling.