Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.24.057570v1?rss=1 Authors: Lillywhite, A., Woodhams, S. G., Watson, D. J. G., Li, L., Burston, J. J., Gowler, P. R. W., Canals, M., Walsh, D. A., Hathway, G. J., Chapman, V. Abstract: Chronic pain states such as osteoarthritis (OA) are often associated with negative affect, including anxiety and depression. This is, in turn, associated with greater opioid analgesic use, potentially contributing to current and future opioid crises. We utilise an animal model to investigate the neurobiological mechanisms underlying increased opioid use associated with high anxiety and chronic pain. Combining a genetic model of negative affect, the Wistar Kyoto (WKY) rat, and intra-articular injection of monosodium iodoacetate (MIA; 1mg), our model of high anxiety and augmented OA-like pain behaviour mirrors the clinical problem. Effects of morphine (0.5-6mg.kg-1) on pain behaviour and spinal nociceptive neuronal activity were determined in WKY rats, and normo-anxiety Wistar rats, 3 weeks after MIA injection. WKY rats developed augmented OA-like pain, and had blunted inhibitory responses to morphine, when compared to Wistar rats. Potential alterations in endogenous opioid function were probed via systemic blockade of opioid receptors with naloxone (0.1-1mg.kg-1), quantification of circulating levels of {beta}-endorphin, and determination of spinal expression of the mu-opioid receptor (MOR). These studies revealed increased opioidergic tone, and increased spinal desensitization of MORs via the master phosphorylation site at serine residue 375, in this model. We demonstrate attenuated MOR function in the absence of previous exogenous opioid ligand exposure in our model of high anxiety and OA-like pain, which may account for reduced analgesic effect of morphine and provide a potential explanation for increased opioid analgesic intake in high anxiety chronic pain patients. Copy rights belong to original authors. Visit the link for more info