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bioRxiv · 10.1101/2025.11.19.689268

Peri-operative pregabalin does not adversely impact experimentaloutcomes in rat models of chronic pain

Di Domenico, F.·Patel, R.·Bannister, K.
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Abstract

IntroductionMultiple mechanisms contribute to the experience of pain where the use of model organisms to dissect mechanistically sensory regulatory circuitry is a vital component of discovering underlying causes of persistent pain in disease states. Such disease states can be modelled in animals using surgical procedures that, ethically, should involve administration of analgesia. However, since basic pain researchers often wish to measure pain-related events, animals may be denied peri-operative analgesia to avoid adversely influencing experimental outcomes. MethodsWe conducted a systematic review of peri-operative analgesia usage in rat spinal nerve ligation (SNL) and cancer-induced bone pain (CIBP) models. Using a combination of behavioural testing and in vivo electrophysiology in the dorsal horn of the spinal cord, we assessed the impact of peri-operative pregabalin on nociceptive behaviours in the acute recovery phase, and behavioural and electrophysiological experimental outcomes in the chronic phase, of rat SNL and CIBP models. ResultsA literature search revealed that, for studies using rat models of SNL or CIBP, only 5.37 % and 12.69 % respectively reported the use of peri-operative analgesia. We then demonstrated that the use of pregabalin as a peri-operative analgesic reduced mechanical hypersensitivity in the acute period following SNL surgery, with no impact on behavioural, electrophysiological or neuropharmacological outcomes in the chronic phase of either model. ConclusionsThis study challenges the basic science researchers reasoning that peri-operative analgesia confounds neurobiological outcomes. The use of peri-operative analgesia should be an important consideration to improve animal welfare in chronic models of pain. SummaryPeri-operative analgesia can improve animal welfare without adversely affecting long term behavioural or pharmacological experimental outcomes in chronic pain models.

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Di Domenico, F., Patel, R., Bannister, K.. 2025-11-19. Peri-operative pregabalin does not adversely impact experimentaloutcomes in rat models of chronic pain. https://doi.org/10.1101/2025.11.19.689268

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