The journal of pain : official journal of the American Pain Society
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Meta Analysis
Characterisation of common genetic variants in P2RX7 and their contribution to chronic pain conditions.
The adenosine triphosphate (ATP)-gated channel P2X7 is encoded by a gene enriched for common nonsynonymous variants. Many of these variants have functional cellular effects, and some have been implicated in chronic pain. In this study, we first systematically characterized all 17 common nonsynonymous variants using whole-cell patch clamp electrophysiology. ⋯ Cumulative allele count analysis did not provide additional insights. In conclusion, our results go beyond reproducing association for rs7958311 with chronic pain and suggest that its unique combination of gain-of-function in channel and loss-of-function in pore activity may explain why it is likely the only common P2RX7 variant with contribution to chronic pain. PERSPECTIVE: This study characterizes all common P2RX7 variants using cellular assays and statistical association analyses with chronic pain, with Markov state modeling of the most robustly associated variant.
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Review Meta Analysis
Conditioned pain modulation and temporal summation of pain in patients with traumatic and non-specific neck pain: a systematic review and meta-analysis.
In patients with neck pain, it is unclear whether pain inhibition and facilitation endogenous pain mechanisms are altered. This systematic review and meta-analysis aimed to improve their understanding by assessing conditioned pain modulation (CPM) and temporal summation of pain (TSP) in patients with neck pain associated with whiplash-associated disorders (WAD) or of a nonspecific neck pain (NSNP) nature compared to pain-free controls. Very low certainty evidence suggests: impaired CPM when assessed remotely in chronic WAD patients (n = 7, 230 patients and 204 controls, standardized mean differences (SMD) = -.47 [-.89 to -.04]; P = .04) but not locally (n = 6, 155 patients and 150 controls; SMD = -.34 [-.68 to .01]; P = .05), impaired CPM in chronic NSNP patients when assessed locally (n = 5, 223 patients and 162 controls; SMD = -.55 [-1.04 to -.06]; P = .04) but not remotely (n = 3, 72 patients and 66 controls; SMD = -.33 [-.92 to .25]; P = .13), TSP not facilitated in either chronic WAD (local TSP: n = 4, 90 patients and 87 controls; SMD = .68 [-.62 to 1.99]) (remote TSP: n = 8, 254 patients and 214 controls; SMD = .18 [-.12 to .48]) or chronic NSNP (local TSP: n = 2, 139 patients and 92 controls; SMD = .21 [-1.00 to 1.41]), (remote TSP: n = 3; 91 patients and 352 controls; SMD = .60 [-1.33 to 2.52]). ⋯ PERSPECTIVE: This review and meta-analysis present the current evidence on CPM and TSP in patients with WAD and NSNP. Standardization of measurement methodology is needed to draw clear conclusions. Subsequently, future studies should investigate the clinical relevance of these measurements as prognostic variables or predictors of treatment success.