Perioperative pregabalin does not alter behavioural or diffuse noxious inhibitory control responses in 2 rat models of chronic pain
Francesca Di Domenico, Mateusz W. Kucharczyk, Ryan Patel, Kirsty BannisterAbstract
Introduction:
Multiple 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 perioperative analgesia to avoid adversely influencing experimental outcomes.
Methods:
We conducted a structured review of perioperative 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 perioperative pregabalin on nociceptive behaviours in the acute recovery phase, and behavioural and electrophysiological experimental outcomes in the established phase, of rat SNL and CIBP models.
Results:
A literature search revealed that, for studies using rat models of SNL or CIBP, only 5.37% and 12.69%, respectively, reported the use of perioperative analgesia. We then demonstrated that the use of pregabalin as a perioperative analgesic reduced mechanical hypersensitivity in the acute period after SNL surgery, with no impact on behavioural, electrophysiological, or neuropharmacological outcomes in the established phase of either model.
Conclusions:
This study challenges the basic science researcher's reasoning that perioperative analgesia confounds neurobiological outcomes. The use of perioperative analgesia should be an important consideration to improve animal welfare in chronic models of pain.