Acute Pain

Purpose of reviewOptimal treatment requires a thorough understanding of all factors contributing to pain in the individual patient. In this review, we investigate the influence of cultural frameworks on pain experience and management.Recent findingsThe loosely defined concept of culture in pain management integrates a predisposing set of diverse biological, psychological and social characteristics shared within a group. Cultural and ethnic background strongly influence the perception, manifestation, and management of pain. In addition, cultural, racial and ethnic differences continue to play a major role in the disparate treatment of acute pain. A holistic and culturally sensitive approach is likely to improve pain management outcomes, will better cover the needs of diverse patient populations and help reduce stigma and health disparities. Mainstays include awareness, self-awareness, appropriate communication, and training.

Pain affects millions worldwide, posing significant challenges in diagnosis and treatment. Despite advances in understanding pain mechanisms, there remains a critical need for validated biomarkers to enhance diagnosis, prognostication, and personalized therapy. This review synthesizes recent advancements in identifying and validating acute and chronic pain biomarkers, including imaging, molecular, sensory, and neurophysiological approaches. We emphasize the emergence of composite, multimodal strategies that integrate psychosocial factors to improve the precision and applicability of biomarkers in chronic pain management. Neuroimaging techniques like MRI and positron emission tomography provide insights into structural and functional abnormalities related to pain, while electrophysiological methods like electroencepholography and magnetoencepholography assess dysfunctional processing in the pain neuroaxis. Molecular biomarkers, including cytokines, proteomics, and metabolites, offer diagnostic and prognostic potential, though extensive validation is needed. Integrating these biomarkers with psychosocial factors into clinical practice can revolutionize pain management by enabling personalized treatment strategies, improving patient outcomes, and potentially reducing healthcare costs. Future directions include the development of composite biomarker signatures, advances in artificial intelligence, and biomarker signature integration into clinical decision support systems. Rigorous validation and standardization efforts are also necessary to ensure these biomarkers are clinically useful. Large-scale collaborative research will be vital to driving progress in this field and implementing these biomarkers in clinical practice. This comprehensive review highlights the potential of biomarkers to transform acute and chronic pain management, offering hope for improved diagnosis, treatment personalization, and patient outcomes.

The number of individuals suffering from severe chronic pain and its social and financial impact is staggering. Without significant advances in our understanding of how acute pain becomes chronic, effective treatments will remain out of reach. This mini review will briefly summarize how critical signaling pathways initiated during the early phases of peripheral nervous system inflammation/ neuroinflammation establish long-term modifications of sensory neuronal function. Together with the recruitment of non-neuronal cellular elements, nociceptive transduction is transformed into a pathophysiologic state sustaining chronic peripheral sensitization and pain. Inflammatory mediators, such as nerve growth factor (NGF), can lower activation thresholds of sensory neurons through posttranslational modification of the pain-transducing ion channels transient-receptor potential TRPV1 and TRPA1. Performing a dual role, NGF also drives increased expression of TRPV1 in sensory neurons through the recruitment of transcription factor Sp4. More broadly, Sp4 appears to modulate a nociceptive transcriptome including TRPA1 and other genes encoding components of pain transduction. Together, these findings suggest a model where acute pain evoked by peripheral injury-induced inflammation becomes persistent through repeated cycles of TRP channel modification, Sp4-dependent overexpression of TRP channels and ongoing production of inflammatory mediators.

BackgroundNaV1.8 channels, expressed in peripheral nociceptors, mediate sustained pain signaling. Their inhibition offers a potential opioid-sparing strategy for postoperative pain, although efficacy and safety remain incompletely defined. We synthesized randomized evidence for suzetrigine versus placebo in postoperative pain.MethodsWe conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant meta-analysis of randomized controlled trials comparing suzetrigine (a NaV1.8 inhibitor) versus placebo in surgical patients. The primary outcome was 24-hour pain with the Numeric Pain Rating Scale; secondary outcomes included 48-hour pain, change-from-baseline, and adverse events. Risk of bias was assessed with the Cochrane Risk of Bias 2 tool, and for analyses, we used Hartung-Knapp models with heterogeneity and prediction intervals reported. Random-effects models used Hartung-Knapp adjustments (2-sided α = 0.05).ResultsWe included 4 randomized datasets across 2 phase 3 publications (n = 1584; 1009 intervention, 575 placebo). The mean participant age was 44.9 years; 92.3% were women. Procedures included abdominoplasty (n = 823) and bunionectomy (n = 761). Suzetrigine significantly reduced pain at 24 hours (mean difference = -0.93; 95% confidence interval [CI], -1.38 to -0.48; I2 = 66.0%) and 48 hours (mean difference = -1.02; 95% CI, -1.32 to -0.72; I2 = 11.8%). Analyses of change-from-baseline confirmed consistent benefit. Subgroup analyses revealed similar effects across surgery types. A lower incidence of nausea (risk ratio = 0.63; 95% CI, 0.42-0.95) and dizziness (risk ratio = 0.57; 95% CI, 0.34-0.96) was observed in the suzetrigine group, with no significant differences in headache, vomiting, or constipation. Meta-regressions showed no moderation by sample size or publication year. Risk of bias was low in 2 studies and raised "some concerns" in 2.ConclusionSuzetrigine produced modest reductions in pain at 24 to 48 hours versus placebo. Because opioid consumption was not consistently reported, no conclusions can be drawn regarding opioid-sparing.