Alterations in endogenous opioid functional measures in chronic back pain

Abstract

The absence of consistent end organ abnormalities in many chronic pain syndromes has led to a search for maladaptive CNS mechanisms that may explain their clinical presentations and course. Here, we addressed the role of brain regional μ-opioid receptor-mediated neurotransmission, one of the best recognized mechanisms of pain regulation, in chronic back pain in human subjects. We compared μ-opioid receptor availability in vivo at baseline, during pain expectation, and with moderate levels of sustained pain in 16 patients with chronic nonspecific back pain (CNBP) and in 16 age- and gender-matched healthy control subjects, using the μ-opioid receptor-selective radioligand [(11)C]carfentanil and positron emission tomography. We found that CNBP patients showed baseline increases in thalamic μ-opioid receptor availability, contrary to a previously studied sample of patients diagnosed with fibromyalgia. During both pain expectation and sustained pain challenges, CNBP patients showed regional reductions in the capacity to activate this neurotransmitter system compared with their control sample, further associated with clinical pain and affective state ratings. Our results demonstrate heterogeneity in endogenous opioid system functional measures across pain conditions, and alterations in both receptor availability and endogenous opioid function in CNBP that are relevant to the clinical presentation of these patients and the effects of opioid analgesics on μ-opioid receptors.

Figures

Figure 1.

Increased thalamic MOR BPND in CNBP patients. Patients with CNBP demonstrated significant increases in MOR BPND in the right thalamus (R thal) and left thalamus (L thal). A, B, The thalamic clusters are shown in radiological convention in axial (Z = 5; A) and coronal planes (Y = −14; B). C, Plots of average cluster MOR BPND values for HC subjects (empty circles, N = 16) and CNBP patients (filled circles, N = 16).

Figure 2.

Associations between thalamic MOR BPND and positive affect and gray matter in CNBP patients. A, B, Significant negative correlations were found between MOR BPND and positive affect as measured by PANAS in the right thalamus (R thal; A) and left thalamus (L thal; B). C, D, The thalamic MOR BPND was also negatively correlated with gray matter volume in the right (C) and left thalamus (D).

Figure 3.

Reductions in brain regional MOR BPND in patients with FM. A–C, Significant reductions in MOR BPND, compared with controls, were observed in the right thalamus (R thal; Y = −11; A), the right nucleus accumbens (R nacc) and left nucleus accumbens (L nacc; Y = 15; B), the left amygdala (L amy)/left hippocampus (L hipp; Y = −9; C), and the left insula. D, Plots of average cluster MOR BPND values for HC subjects (empty circles, N = 19) and FM patients (filled circles, N = 19).

Figure 4.

Differential effects of pain expectation and sustained experimental muscle pain on MOR BPND in HC subjects and CNBP patients. A–C, Significant differences in MOR activation were observed between HC and CNBP samples in the left amygdala (L amy) during pain expectation, shown in coronal (Y = −6; A) and axial planes (Z = −15; B), and during sustained pain, shown in coronal plane (Y = −12; C). D, Plots of average MOR BPND changes for HC subjects (empty circles, N = 16) and CNBP patients (filled circles, N = 15).