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.

Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1. Relationship of 11C-DPN binding to chronic pain perception and acute pain thresholds.

The Volume of Distribution (VD), as a proxy of 11C-DPN binding, was adjusted for a number of nuisance variables in each analysis (see Methods). (a) Whole-brain SPM regression analysis of McGill sensory pain scores as a predictor of 11C-DPN binding (patients only, n = 17). Images are displayed at a voxel threshold of p < 0.001 uncorrected and a cluster threshold equating to the size of the significant cluster. (b) For illustrative purposes, subsequent extraction of mean VD values from the caudate nucleus was corrected for the same nuisance variables and plotted against McGill sensory pain scores. (c) Pain threshold (laser energy in W cm-2 required to elicit the lowest pain sensation) regressed on VD values (mean across all voxels in the caudate ROI) after correction for nuisance variables. Regression line illustrates fits for the pooled data across groups (patients and controls, n = 26).