title: Striatal opioid receptor availability is related to acute and chronic pain perception in arthritis: does opioid adaptation increase resilience to chronic pain?
abstract: The 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.
authors.affiliation: 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.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Brown
authors.forename: Julian
authors.initials: J
authors.lastname: Matthews
authors.forename: Michael
authors.initials: M
authors.lastname: Fairclough
authors.forename: Adam
authors.initials: A
authors.lastname: McMahon
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Barnett
authors.forename: Ali
authors.initials: A
authors.lastname: Al-Kaysi
authors.forename: Wael
authors.initials: W
authors.lastname: El-Deredy
authors.forename: Anthony K P
authors.initials: AKP
authors.lastname: Jones
mesh_terms: D000328:Adult; D000368:Aged; D001168:Arthritis / Q000150:complications*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D059350:Chronic Pain / Q000209:etiology* / Q000473:pathology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004174:Diprenorphine / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009292:Narcotic Antagonists / Q000493:pharmacokinetics; D010104:Oxygen Radioisotopes / Q000493:pharmacokinetics; D058748:Pain Perception / Q000502:physiology*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010487:Periaqueductal Gray / Q000378:metabolism; D049268:Positron-Emission Tomography; D011957:Receptors, Opioid / Q000378:metabolism*; D011795:Surveys and Questionnaires
chemical_list: D002250:Carbon Radioisotopes; D009292:Narcotic Antagonists; D010104:Oxygen Radioisotopes; D011957:Receptors, Opioid; D004174:Diprenorphine