Pain
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The insular cortex (IC) processes various sensory information, including nociception, from the trigeminal region. Repetitive nociceptive inputs from the orofacial area induce plastic changes in the IC. Parvalbumin-immunopositive neurons (PVNs) project to excitatory neurons (pyramidal neurons [PNs]), whose inputs strongly suppress the activities of PNs. ⋯ Then, the IC received ROS to induce LTP of IPSCs from PVNs to PNs, and we evaluated pain-related behaviors. Compared to those before ROS, the pain-related behaviors were further reduced after ROS. These results suggest that LTP induction of PVN→PN synapses in the IC could be a possible treatment for abnormal pain in the orofacial area.
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Recent evidence highlights that monetary rewards can increase the precision at which healthy human volunteers can detect small changes in the intensity of thermal noxious stimuli, contradicting the idea that rewards exert a broad inhibiting influence on pain perception. This effect was stronger with contingent rewards compared with noncontingent rewards, suggesting a successful learning process. In the present study, we implemented a model comparison approach that aimed to improve our understanding of the mechanisms that underlie thermal noxious discrimination in humans. ⋯ In addition, reinforcement learning models indicated a temporal evolution of discriminative abilities reflected by a trial-by-trial increase of perceived signal strength only with contingent rewards but not with noncontingent rewards. Modelling of separate learning rates for positive and negative prediction errors indicated that this temporal evolution of discriminative abilities was driven by positive reward prediction errors. These results might indicate increased sensitivity towards better-than-expected outcomes in the temporal adaptation of pain discrimination abilities to a rewarding context in humans.
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Rapid declines in opioid analgesics dispensed in American communities since 2011 raise concerns about inadequate access to effective pain management among patients for whom opioid therapies are appropriate, especially for those living in racial/ethnic minority and socioeconomically deprived communities. Using 2011 to 2021 national data from the Automated Reports and Consolidated Ordering System and generalized linear models, this study examined quarterly per capita distribution of oxycodone, hydrocodone, and morphine (in oral morphine milligram equivalents [MMEs]) by communities' racial/ethnic and socioeconomic profiles. Communities (defined by 3-digit-zip codes areas) were classified as "majority White" (≥50% self-reported non-Hispanic White population) vs "majority non-White." Community socioeconomic deprivation was measured by quartiles of population-weighted Social Deprivation Index. ⋯ The lower distribution in majority non-White communities was statistically significant across all socioeconomic deprivation levels and over all study years. Availability of commonly prescribed opioid analgesics was substantially lower in majority non-White communities than in majority White communities across all levels of socioeconomic deprivation. Policies governing opioid analgesic availability warrant careful consideration and potential adjustments.
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Placebo hypoalgesia and nocebo hyperalgesia, which exemplify the impact of expectations on pain, have recently been conceptualised as Bayesian inferential processes, yet empirical evidence remains limited. Here, we explore whether these phenomena can be unified within the same Bayesian framework by testing the predictive role of expectations and their level of precision (ie, expectation confidence) on pain, with both predictors measured at the metacognitive level. Sixty healthy volunteers underwent a pain test (ie, 8 noxious electrical stimuli) before (Baseline) and after (T0, T1, T2) receiving a sham treatment associated with hypoalgesic (placebo), hyperalgesic (nocebo), or neutral (control) verbal suggestions, depending on group allocation. ⋯ This suggests that both placebo and nocebo responses are well described from a Bayesian perspective. A main effect of time for SCR was observed, suggesting habituation to painful stimuli. Our data provide evidence indicating that both placebo hypoalgesia and nocebo hyperalgesia can be unified within the same Bayesian framework in which not only expectations but also their level of precision, both measured at the metacognitive level, are key determinants of the pain inferential process.
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A variety of minimal clinically important difference (MCID) estimates are available to distinguish subgroups with differing outcomes. When a true gold standard is absent, latent class growth curve analysis (LCGC) has been proposed as a suitable alternative for important change. Our purpose was to evaluate the performance of individual and baseline quartile-stratified MCIDs. ⋯ Classification errors in individual MCID estimates most likely result from ceiling effects. Minimal clinically important differences calculated for each baseline quartile are superior to individually calculated MCIDs and should be used when latent class methods are not available. Use of individual MCIDs likely contribute substantial error and are discouraged for clinical application.