Articles: hyperalgesia.
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Curr Opin Anaesthesiol · Aug 2024
ReviewRemifentanil-induced hyperalgesia: the current state of affairs.
Remifentanil-induced hyperalgesia (RIH) is a part of a general opioid-induced hyperalgesia (OIH) syndrome, seemingly resulting from abrupt cessation of continuous remifentanil infusion at rates equal or exceeding 0.3 mcg/kg/min. The intricate mechanisms of its development are still not completely understood. ⋯ Several ways of prevention and management have been suggested, such as slow withdrawal of remifentanil infusion, the addition of propofol, pretreatment with or concomitant administration of ketamine, buprenorphine, cyclooxygenase-2 inhibitors (NSAIDs), methadone, dexmedetomidine. In clinical and animal studies, these strategies exhibited varying success, and many are still being investigated.
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Randomized Controlled Trial
Theta Burst Stimulation of the Human Motor Cortex Modulates Secondary Hyperalgesia to Punctate Mechanical Stimuli.
Many chronic pain conditions show evidence of dysregulated synaptic plasticity, including the development and maintenance of central sensitization. This provides a strong rationale for neuromodulation therapies for the relief of chronic pain. However, variability in responses and low fidelity across studies remain an issue for both clinical trials and pain management, demonstrating insufficient mechanistic understanding of effective treatment protocols. ⋯ By defining the underlying mechanisms of TBS-driven synaptic plasticity in the nociceptive system, we offer new insight into disease mechanisms and provide targets for promoting functional recovery and repair in chronic pain. For clinical applications, this knowledge is critical for development of more efficacious and mechanisms-based neuromodulation protocols, which are urgently needed to address the chronic pain and opioid epidemics.
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Oxaliplatin-induced peripheral neuropathy (OIPN) is a dose-limiting toxicity characterised by mechanical allodynia and thermal hyperalgesia, without any licensed medications. ART26.12 is a fatty acid-binding protein (FABP) 5 inhibitor with antinociceptive properties, characterised here for the prevention and treatment of OIPN. ART26.12 binds selectively to FABP5 compared to FABP3, FABP4, and FABP7, with minimal off-target liabilities, high oral bioavailability, and a NOAEL of 1,000 mg/kg/day in rats and dogs. ⋯ These results show promise that ART26.12 is a safe and well-tolerated candidate for the treatment and prevention of OIPN through lipid modulation. PERSPECTIVE: Inhibition of fatty acid-binding protein 5 (FABP5) is a novel target for reducing pain associated with chemotherapy. ART26.12 is a safe and well-tolerated small molecule FABP5 inhibitor effective at preventing and reducing pain induced with oxaliplatin through lipid modulation and activation of cannabinoid receptors.
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Excessive alcohol consumption in adolescence can disrupt neural development and may augment pain perception. Recent studies have shown that the nucleus accumbens (NAc) shell is involved in mediating pain sensitivity after peripheral inflammation in rodent models of chronic pain and alcohol use disorder. Interestingly, there have been very few studies examining the impact of chronic ethanol exposure during adolescence on pain sensitivity in adulthood. ⋯ With phasic stimulation, aCIE rats also showed greater dopamine release compared with AIR-exposed rats. Inhibition of dopamine transmission targeted in the NAc shell reversed the aCIE-associated facilitation of mechanical allodynia in both sexes. These data suggest that aCIE exposure exacerbates pain sensitivity during withdrawal in an accumbal dopamine-dependent manner.
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Comparative Study
Healthy women show more experimentally induced central sensitization compared with men.
Women more often experience chronic pain conditions than men. Central sensitization (CS) is one key mechanism in chronic pain that can differ between the sexes. It is unknown whether CS processes are already more pronounced in healthy women than in men. ⋯ The objective CS proxy differences indicate that dorsal horn CS processes are more pronounced in healthy women. The even larger sex differences in subjective CS proxies potentially reflect greater supraspinal influence in women. This study shows that sex differences are present in experimentally induced CS in healthy subjects, which might contribute to women's vulnerability for chronic pain.