Background & Aims: Pain research suffers from a significant translational gap, partially attributable to a focus on sensory over affective aspects of pain. To help combat this, we recently modelled the interaction between anxiety and osteoarthritis (OA) in a rat strain with anxiety-like behaviours (Wistar Kyoto; WKY). WKY rats develop an augmented widespread pain phenotype in the monoiodoacetate (MIA) model of OA, mirroring the clinical population. Here we utilise in vivo electrophysiology and ex vivo analyses to demonstrate altered spinal opioid signalling in this model.
Methods:  This study used 4 experimental groups: Anxiety+OA (WKY/MIA); anxiety+no pain (WKY/saline); no anxiety+OA (Wistar/MIA); no anxiety+no pain (Wistar/saline). Adult male rats received a unilateral intra-articular injection of 1mg MIA or saline, and alterations in pain behaviour (paw withdrawal thresholds) and anxiety status (elevated plus maze) were assessed over 21 days. Responses to cumulative doses of systemic morphine were then assessed via in vivo single unit spinal recordings. In a separate group of rats, spinal expression of spinal mu opioid receptors (MOR) was assessed via Western blotting.
Results: WKY rats display a basal anxiety-like phenotype. MIA injection does not significantly alter anxiety in either strain. Augmented pain behaviour in the WKY-MIA model is associated with increased wind-up of spinal neurons, and a decreased response to systemic morphine, demonstrating increased spinal excitability in this model. Ex vivo analyses reveal alterations in MOR expression.
Conclusions: Morphine has reduced efficacy in rats with anxiety-like behaviour and augmented OA-like pain, with potential implications for clinical prescription of opioids.

DIFFERENTIAL OPIOID FUNCTION IN A RAT MODEL OF ANXIETY-LIKE BEHAVIOUR AND AUGMENTED OSTEOARTHRITIS PAIN