nociceptive signals dependent on spinal NMDAR through several possible mechanisms. Through behavioral, pharmacological, and molecular approaches, our study in male rats has revealed several key findings: (1) neurons located in spinal cord laminae I and II express functional Panx1 channels in both neuropathic and sham rats. These channels can open (indicated by YOPRO-1 uptake) through the stimulation of NMDARs with intrathecal NMDA; (2) intrathecal NMDA leads to increased expression of pSrc and pPanx1 in dorsal horn neurons. This elevation exacerbates existing mechanical hyperalgesia in nerve-injured rats; (3) inhibition of Src with intrathecal PP2 or blockade of Panx1 with intrathecal 10Panx effectively mitigates NMDA-induced effects and reduces the spontaneous mechanical hyperalgesia of nerve-injured rats. Notably, while 10Panx successfully alleviates hyperalgesia, it does not alter pSrc expression; and (4) NMDA-stimulated YOPRO-1 uptake in neurons of laminae I-II of spinal cord slice

nociceptive signals dependent on spinal NMDAR through several possible mechanisms. Through behavioral, pharmacological, and molecular approaches, our study in male rats has revealed several key findings: (1) neurons located in spinal cord laminae I and II express functional Panx1 channels in both neuropathic and sham rats. These channels can open (indicated by YOPRO-1 uptake) through the stimulation of NMDARs with intrathecal NMDA; (2) intrathecal NMDA leads to increased expression of pSrc and pPanx1 in dorsal horn neurons. This elevation exacerbates existing mechanical hyperalgesia in nerve-injured rats; (3) inhibition of Src with intrathecal PP2 or blockade of Panx1 with intrathecal 10Panx effectively mitigates NMDA-induced effects and reduces the spontaneous mechanical hyperalgesia of nerve-injured rats. Notably, while 10Panx successfully alleviates hyperalgesia, it does not alter pSrc expression; and (4) NMDA-stimulated YOPRO-1 uptake in neurons of laminae I-II of spinal cord slice

evaluate the performance of individual and baseline quartile-stratified MCIDs. The current study included data from 346 persons with baseline and 12-month postoperative outcome data from KASTPain, a no-effect randomized clinical trial conducted on persons with knee arthroplasty and pain catastrophizing. Subgroup trajectories from LCGC were used as a gold standard comparator. Minimal clinically important difference–specific trajectories of recovery were calculated for the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain, Disability and EuroQol-5 Dimension Visual Analogue Scale of self-reported health. The latent Kappa (Kl) chance-corrected agreement between MCIDs and LCGCs were estimated to indicate which MCID method was best at detecting important change. For all 3 outcomes, the average latent class probabilities ranged from 0.90 to 0.99, justifying the use of LCGCs as a gold standard. The Kl for LCGC and individual MCIDs ranged from 0.21 (95% CI = 0.13, 0.28

An abstract is unavailable.

hared environmental or genetic factors might account for any observed association. Around 3000 participants from the TwinsUK with CWP information and measures of carotid–femoral pulse wave velocity (cfPWV), carotid intima–media thickness (cIMT), and plaque were considered. The relationship between CWP and cfPWV, cIMT, and plaque was determined. UK Biobank data were used to replicate the association. Cholesky decomposition and multivariate pathway twin models were examined. Using a 2-sample Mendelian randomisation approach, the causal association between CWP and coronary artery disease was assessed. TwinsUK participants demonstrated a significant association between CWP and increased cfPWV consistent with arterial stiffening (OR = 1.35, P-value = 0.012), as well as the presence of carotid plaque (OR = 1.45, P-value = 0.8e-5). The twin modelling showed a common latent component and pathway underlying CWP, cfPWV, and carotid plaque, with genetic factors accounting for 68% and 90% of the l