Refining capsaicin-induced pain models: A comprehensive analysis of preclinical practices and their translational...

Pain remains a significant clinical challenge despite advances in mechanistic understanding. Animal models have been instrumental in advancing our understanding of pain mechanisms, however translating this understanding into positive clinical outcomes has been lacking. Capsaicin, a TRPV1 agonist and active component of chili peppers, is widely used in pre-clinical pain studies to evoke nociceptive responses. This systematic review investigates how capsaicin is currently used as a nociceptive stimulus in preclinical behavioural models of pain. We examine the purpose of capsaicin use, species and sexes of animals tested, methods of administration, dosage, and the types of pain behaviours assessed. Capsaicin-evoked behaviours are primarily used to understand TRPV1 specific pain mechanisms and screen analgesic compounds. We report male rodent studies are the dominant subject for capsaicin-induced behaviours and that within the limited studies involving female rodents, conflating data regarding sex specific effects exists. Very few novel behavioural techniques have been introduced, with studies heavily relying on behavioural measures such as von Frey sensitivity, hindpaw movements and thermal withdrawal latencies. We also report no significant correlation between increasing capsaicin dose and time of observed behavioural sensitivity, suggesting lower doses should be considered. We believe the data collected and reported here is useful to future researchers in both assessment of model relevance and informing experimental design. By analysing current practices and identifying areas for improvement in experimental design, this review aims to inform methodology for future studies and improve animal welfare.