Pain
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Back pain is a common and recurrent health complaint in adolescence. Psychosocial factors may be associated with the onset and persistence of back pain symptoms. This systematic review aims to determine the association between bullying victimization and back pain in young people. ⋯ Our synthesis of evidence found a weak-moderate association between bullying victimization and back pain in young people. Methodological shortcomings and heterogeneity in the field limit causal inference. Future longitudinal studies are required.
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Randomized Controlled Trial
METHA-NeP: effectiveness and safety of methadone for neuropathic pain: a controlled randomized trial.
In this randomized, double-blind, parallel placebo-controlled clinical trial, we evaluated the efficacy of methadone as an add-on therapy for people with chronic neuropathic pain (NP). Eighty-six patients were randomly assigned to receive methadone or placebo for 8 weeks. The primary outcome was the proportion of participants achieving at least 30% pain relief from baseline using a 100-mm pain Visual Analogue Scale. ⋯ No serious adverse events or deaths occurred. Discontinuation due to adverse events was reported in 2 participants in the methadone and none in the placebo arm. Methadone use as an add-on to an optimized treatment for NP with first- and/or second-line drugs provided superior analgesia, improved sleep, and enhanced global impression of change, without being associated with significant serious adverse effects that would raise safety concerns.
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Review
Discordance between preclinical and clinical testing of Na V 1.7-selective inhibitors for pain.
The voltage-gated sodium channel Na V 1.7 plays an important role in pain processing according to genetic data. Those data made Na V 1.7 a popular drug target, especially since its relatively selective expression in nociceptors promised pain relief without the adverse effects associated with broader sodium channel blockade. Despite encouraging preclinical data in rodents, Na V 1.7-selective inhibitors have not yet proven effective in clinical trials. ⋯ Nearly all preclinical studies gave a single dose of drug unlike the repeat dosing used clinically, thus precluding preclinical data from demonstrating whether tolerance or other slow processes occur. In summary, preclinical testing of Na V 1.7-selective inhibitors aligned poorly with clinical testing. Beyond issues that have already garnered widespread attention in the pain literature, our results highlight the treatment regimen and choice of pain model as areas for improvement.
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Repetitive ischemia with reperfusion (I/R) injury is a common cause of myalgia. Ischemia with reperfusion injuries occur in many conditions that differentially affect males and females including complex regional pain syndrome and fibromyalgia. Our preclinical studies have indicated that primary afferent sensitization and behavioral hypersensitivity caused by I/R injury may be due to sex-specific gene expression in the dorsal root ganglia (DRG) and distinct upregulation of growth factors and cytokines in the affected muscles. ⋯ AUF1 knockdown was able to specifically inhibit repeated I/R-induced gene expression in females potentially downstream of prolactin receptor signaling. Data suggest RNA-binding proteins such as pAUF1 may underlie the sex-specific effects on DRG gene expression that modulates behavioral hypersensitivity after repeated I/R injury through prolactin signaling. This study may aid in finding distinct receptor differences related to the evolution of acute to chronic ischemic muscle pain development between sexes.
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Understanding how large language model (LLM) recommendations vary with patient race/ethnicity provides insight into how LLMs may counter or compound bias in opioid prescription. Forty real-world patient cases were sourced from the MIMIC-IV Note dataset with chief complaints of abdominal pain, back pain, headache, or musculoskeletal pain and amended to include all combinations of race/ethnicity and sex. Large language models were instructed to provide a subjective pain rating and comprehensive pain management recommendation. ⋯ Race/ethnicity and sex did not influence LLM recommendations. This study suggests that LLMs do not preferentially recommend opioid treatment for one group over another. Given that prior research shows race-based disparities in pain perception and treatment by healthcare providers, LLMs may offer physicians a helpful tool to guide their pain management and ensure equitable treatment across patient groups.