PAIN®最新文献

Abstract: 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 a between-subject design, 54 healthy human volunteers took part in a pain discrimination task with monetary rewards either contingent or noncontingent on successful discrimination of small changes in the intensity painful heat stimulation. We used models from 2 traditions in decision-making research, perceptual decision-making, and instrumental learning. Replicating the previous findings, only rewards contingent on behavior enhanced pain discrimination. Drift diffusion modelling revealed increased sensory signal strength and decreased response caution and nondecision times as mechanisms underlying this effect of contingent rewards on pain discrimination. 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.

Abstract: 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. This study investigated how PVNs in the IC modulate pain-related behaviors using optogenetics. To evaluate the effect of PVN activation on pain-related behavior, we applied nociceptive heat stimulation to the whisker pads of PV-Cre rats that received an injection of adeno-associated virus-Flex-channelrhodopsin-2-mCherry into the IC. Exposure to nociceptive heat stimulation significantly increased the amount of pain-related escape behavior, and PVN activation by optogenetics did not significantly decrease pain-related behavior. We next examined the possibility that long-term potentiation (LTP) of PVN→PN synapses suppresses pain-related behaviors. We recorded light-evoked inhibitory postsynaptic currents (IPSCs) from PNs in the IC slice preparation to examine whether optogenetic activation of PVNs can induce LTP. Repetitive optogenetic stimulation (ROS) of PVNs in a manner analogous to theta burst stimulation increased the amplitude of IPSCs for at least 50 minutes. Long-term potentiation was induced by either the -45 or -60 mV membrane potential 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.

Abstract: Studies on pain in preterm infants have usually been confined to observations of painful procedures, and information from extremely preterm infants is limited. Using registry data from a Swedish nationwide cohort, this study explored the epidemiology of pain in very preterm infants, its causes, assessments, and treatment strategies. We included liveborn infants <32 weeks' gestational age (GA) discharged between January 2020 and June 2024. Proportions of infants exposed to potentially painful procedures, experiencing pain, assessed with pain scales, and receiving pharmacological treatment were calculated by each postnatal day. Among 3686 infants (mean birthweight 1176 g, GA 28.2 weeks), 11.6% had a painful condition and 84.1% were exposed to at least 1 potentially painful procedure. In total, 74.6% experienced pain, corresponding to 28,137/185,008 (15.2%) days of neonatal care. For every 2-week increase in GA, significantly lower proportions of infants experienced pain. In infants <28 weeks of GA, proportions with reported pain were approximately half the rate of painful procedures, while in infants born at 28 to 31 weeks, reported pain closely matched exposure to painful procedures. Pain scales were used in 75.0% of the infants. Pharmacological pain treatment was administered to 81.7% of infants, primarily topically or orally. Among infants with pain, proportions treated intravenously were larger at higher GAs. Despite effective analgesia/anesthesia, many very preterm infants experience pain. Visualizing pain epidemiology, procedures, conditions, and treatment by postnatal and gestational age may guide clinical management and generate research hypotheses to reduce short- and long-term adverse effects.

Abstract: 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. 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) to 0.52 (95% CI = 0.41, 0.66). Baseline quartile-stratified Kl for WOMAC Pain and Disability were 0.85 (95% CI = 0.78, 0.92) and 0.74 (95% CI = 0.68, 0.83), respectively. 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.

Abstract: 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. Trial-by-trial expectations, their precision, and perceived pain were measured. Skin conductance response (SCR) was also recorded as an autonomic response marker. Bayesian linear mixed models analyses revealed that, for both placebo and nocebo, pain was predicted by expectations alone and by their interaction with expectations precision. In addition, the discrepancy between expected and perceived pain was predicted by expectation precision, with greater alignment between expected and perceived pain when precision was higher. 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.

Abstract: Female sex is a prominent risk factor for chronic pain, although the underlying mechanisms are not fully understood. This cross-sectional study aimed to investigate the relationship between age at menopause, reproductive lifespan, and chronic pain in a sample of postmenopausal women aged 40 to 93 years. Data were collected from the Tromsø study conducted in Norway between 2015 and 2016 (Tromsø7). Chronic pain was assessed using a single question, which formed a sample size of 5741 participants. Chronic widespread pain was evaluated using the more comprehensive Graphical Index of Pain, resulting in a sample size of 5920 women. Premenopausal women and those who experienced menstrual cessation due to chemotherapy/radiation or hormonal intrauterine devices were excluded from the analysis. Adjusted relative risk ratios with 95% confidence intervals were calculated to determine associations. The results showed that early menopause was associated with a 1% increase in the prevalence of chronic pain for each year of earlier onset at menopause (0.992, CI 95% 0.985-0.998). This association was also observed in women who experienced natural menopause only. However, the association between menopause and chronic widespread pain did not reach statistical significance in the fully adjusted analysis (0.996, CI 95% 0.975-1.017). There were no significant associations found between reproductive lifespan and either outcome. In conclusion, the findings suggest that early menopause in postmenopausal women is linked to a higher prevalence of chronic pain. However, reproductive lifespan does not appear to have a significant impact on chronic pain or chronic widespread pain.

Abstract: Quantitative sensory testing (QST) is a set of methods for quantifying somatosensory functioning. Limitations of laboratory-based QST (LQST) include high cost, complexity in training, lack of portability, and time requirements for testing. Translating QST to a home setting could facilitate future research and clinical care. The objective of this study was to develop a home QST (HQST) tool-kit that is cost-effective, easy to use, and detects changes in sensory and pain processing. Thirty-two young healthy adults underwent sensory testing on their nondominant forearm using standard in-person LQST, followed by "simulated HQST" using video guidance in a separate room from the investigator before and after application of either a lidocaine or capsaicin cream. We observed good agreement between HQST and LQST scores, with significant correlations observed between the pinprick, pressure, cold and heat measures (|ρ| range = 0.36-0.54). The participants rated the HQST protocol as highly acceptable and safe but can be improved in future implementations. Home QST was able to detect hypoesthesia to vibration after lidocaine cream application ( P = 0.024, d = 0.502) and could detect hypoalgesia and hyperalgesia to pressure and heat pain sensitivity tests after application of lidocaine and capsaicin creams, respectively ( P -value range = <0.001-0.036, d -value range = 0.563-0.901). Despite limitations, HQST tool-kits may become a cost-effective, convenient, and scalable approach for improving sensory profiling in clinical care and clinical research.

Abstract: Pediatric chronic pain, particularly chronic postsurgical pain (CPSP), poses a significant public health challenge, impacting 20% of pediatric populations. While several presurgical predictors have been identified, there is a scarcity of data on long-term outcomes, especially beyond 1 to 2 years postsurgery. Previous research primarily focuses on North American children, creating gaps in understanding CPSP outcomes in diverse health systems, such as in Spain. This study, registered as NCT04735211, investigates CPSP in 159 children and adolescents (mean age = 12.4 years, 37.1% girls, retention rate = 65%) undergoing various surgeries in Spain. The objectives include examining CPSP prevalence (Numerical Rating Scale ≥ 4) at 3, 6, 12, and 24 months, exploring postsurgical pain trajectories through group-based trajectory modeling, and identifying potential presurgical predictors for CPSP (pain intensity, pain catastrophizing, pain anxiety, fear of pain, kinesiophobia, health-related quality of life, pain interference, and physical activity), using multiple logistic regressions. Results show a CPSP prevalence of 41% at 3 months, decreasing to 14% at 24 months. Presurgical factors including pain intensity (adjusted odds ratio [aOR] = 1.25, 95% confidence interval [CI] = 1.02-1.53), pain catastrophizing (aOR = 1.06, 95% CI = 1.00-1.13), and pain anxiety (aOR = 1.06, 95% CI = 1.02-1.11) were associated with CPSP at 3 months. Group-based trajectory modeling revealed 3 postsurgical pain trajectories: Low Pain with Rapid Recovery Group (30.2%), Moderate Pain with Recovery Group (53.5%), and High Pain with Slow Recovery Group (16.3%), with group differences in presurgical predictors, excluding physical activity. This study contributes valuable insights into CPSP, emphasizing the need for long-term follow-up. The findings could inform the implementation of preventive programs for CPSP into diverse health systems.