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Striatal opioid receptor availability is related to acute and chronic pain perception in arthritis: does opioid adaptation increase resilience to chronic pain?

Brown, Christopher A.a,f,*; Matthews, Julianb; Fairclough, Michaelb; McMahon, Adamb; Barnett, Elizabethb; Al-Kaysi, Alic; El-Deredy, Waeld,e; Jones, Anthony K.P.f

doi: 10.1097/j.pain.0000000000000299
Research Paper

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 11C-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.

Supplemental Digital Content is Available in the Text.Relationships between chronic pain and opioid receptor availability provide initial human evidence of an upregulation of opioid receptors in the brain in chronic pain.

aCamPAIN Group, Division of Anaesthesia, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom

bWolfson Molecular Imaging Centre, University of Manchester, Manchester, United Kingdom

cDepartment of Anaesthesia, Southport and Ormskirk Hospitals, Southport, Merseyside, United Kingdom

dSchool of Psychological Sciences, University of Manchester, Manchester, United Kingdom

eDepartment of Civil Biomedical Engineering, University of Valparaiso, Valparaiso, Chile

fHuman Pain Research Group, Institute of Brain, Behaviour and Mental Health, University of Manchester, Salford, United Kingdom

Corresponding author. Address: CamPain Group, Division of Anaesthesia, University of Cambridge, Box 93, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom. Tel: 01223 256995; fax: 01223 217 887. E-mail address: cb802@cam.ac.uk (C. A. Brown).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.painjournalonline.com).

Received February 19, 2015

Received in revised form June 18, 2015

Accepted July 06, 2015

© 2015 International Association for the Study of Pain
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