• Christopher A Brown, Julian Matthews, Michael Fairclough, Adam McMahon, Elizabeth Barnett, Ali Al-Kaysi, Wael El-Deredy, and JonesAnthony K PAKP.
• CamPAIN Group, Division of Anaesthesia, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom Wolfson Molecular Imaging Centre, University of Manchester, Manchester, United Kingdom Department of Anaesthesia, Southport and Ormskirk Hospitals, Southport, Merseyside, United Kingdom School of Psychological Sciences, University of Manchester, Manchester, United Kingdom Department of Civil Biomedical Engineering, University of Valparaiso, Valparaiso, Chile Human Pain Research Group, Institute of Brain, Behaviour and Mental Health, University of Manchester, Salford, United Kingdom.
• Pain. 2015 Nov 1; 156 (11): 2267-2275.

AbstractThe experience of pain in humans is modulated by endogenous opioids, but it is largely unknown how the opioid system adapts to chronic pain states. Animal models of chronic pain point to upregulation of opioid receptors (OpR) in the brain, with unknown functional significance. We sought evidence for a similar relationship between chronic pain and OpR availability in humans. Using positron emission tomography and the radiotracer (11)C-diprenorphine, patients with arthritis pain (n = 17) and healthy controls (n = 9) underwent whole-brain positron emission tomography scanning to calculate parametric maps of OpR availability. Consistent with the upregulation hypothesis, within the arthritis group, greater OpR availability was found in the striatum (including the caudate) of patients reporting higher levels of recent chronic pain, as well as regions of interest in the descending opioidergic pathway including the anterior cingulate cortex, thalamus, and periaqueductal gray. The functional significance of striatal changes were clarified with respect to acute pain thresholds: data across patients and controls revealed that striatal OpR availability was related to reduced pain perception. These findings are consistent with the view that chronic pain may upregulate OpR availability to dampen pain. Finally, patients with arthritis pain, compared with healthy controls, had overall less OpR availability within the striatum specifically, consistent with the greater endogenous opioid binding that would be expected in chronic pain states. Our observational evidence points to the need for further studies to establish the causal relationship between chronic pain states and OpR adaptation.

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