Chronic Back Pain Is Associated with Alterations in Dopamine Neurotransmission in the Ventral Striatum

Abstract

Back pain is common in the general population, but only a subgroup of back pain patients develops a disabling chronic pain state. The reasons for this are incompletely understood, but recent evidence implies that both preexisting and pain-related variations in the structure and function of the nervous system may contribute significantly to the development of chronic pain. Here, we addressed the role of striatal dopamine (DA) D2/D3 receptor (D2/D3R) function in chronic non-neuropathic back pain (CNBP) by comparing CNBP patients and healthy controls using PET and the D2/D3R-selective radioligand [(11)C]raclopride. D2/D3R availability was measured at baseline and during a pain challenge, yielding in vivo measures of receptor availability (binding potential, BPND) and DA release (change in BPND from baseline to activated state). At baseline, CNBP patients demonstrated reductions in D2/D3R BPND in the ventral striatum compared with controls. These reductions were associated with greater positive affect scores and pain tolerance measures. The reductions in D2/D3R BPND were also correlated with μ-opioid receptor BPND and pain-induced endogenous opioid system activation in the amygdala, further associated with measures of positive affect, the affective component of back pain and pain tolerance. During the pain challenge, lower magnitudes of DA release, and therefore D2/D3R activation, were also found in the ventral striatum in the CNBP sample compared with controls. Our results show that CNBP is associated with adaptations in ventral striatal D2/D3R function, which, together with endogenous opioid system function, contribute to the sensory and affective-motivational features of CNBP.

Significance statement: The neural systems that underlie chronic pain remain poorly understood. Here, using PET, we provide insight into the molecular mechanisms that regulate sensory and affective dimensions of pain in chronic back pain patients. We found that patients with back pain have alterations in brain dopamine function that are associated with measures of pain sensitivity and affective state, but also with brain endogenous opioid system functional measures. These findings suggest that brain dopamine-opioid interactions are involved in the pathophysiology of chronic pain, which has potential therapeutic implications. Our results may also help to explain individual variation in susceptibility to opioid medication misuse and eventual addiction in the context of chronic pain.

Keywords: amygdala; chronic pain; dopamine; endogenous opioid; striatum.

Copyright © 2015 the authors 0270-6474/15/359957-09$15.00/0.

Figures

Figure 1.

Levels of striatal D2/D3R BPND in CNBP patients and HCs. Significant reductions in D2/D3R BPND, compared with HC sample, were observed at baseline in the right ventral striatum. A, Top, Significant region in the ventral striatum and plots of average D2/D3R BPND values for HC subjects (empty circles) and CNBP patients (filled circles). The D2/D3R BPND in this region was negatively correlated with positive affect and pain tolerance measures in CNBP patients (B, bottom).

Figure 2.

Sustained experimental muscle pain-induced changes in D2/D3R BPND (DA activation) in the striatum, in HC subjects and CNBP patients. In the entire sample, significant D2/D3R activation was observed bilaterally in the ventral and dorsal striatum, with peak effects localized in the left caudate, left putamen, and right nucleus accumbens (A). A significant group × condition interaction in D2/D3R activation was observed in the right ventral striatum, with peak in the right ventral caudate (B). Illustrated on the right are plots of average regional D2/D3R activation in the areas showing significant D2/D3R activation in the entire sample (A) and in the area that showed a significant group × condition interaction (B).

Figure 3.

Associations between baseline D2/D3R BPND in the right ventral striatum and MOR functional measures in the amygdala in CNBP patients. In patients with CNBP, significant associations were found between baseline D2/D3R BPND in the right ventral striatum and baseline MOR BPND in the right (A) and left (B) amygdala and MOR activation during experimental pain in the left amygdala (C). The r and p-values were calculated using data extracted from the significant regions in the voxel-by-voxel regression analyses.