Reduced basal ganglia μ-opioid receptor availability in trigeminal neuropathic pain: a pilot study

Marcos Fabio DosSantos, Ilkka Kristian Martikainen, Thiago Dias Nascimento, Tiffany M Love, Misty Dawn Deboer, Eric C Maslowski, André Antonio Monteiro, Maurice Borges Vincent, Jon-Kar Zubieta, Alexandre F DaSilva, Marcos Fabio DosSantos, Ilkka Kristian Martikainen, Thiago Dias Nascimento, Tiffany M Love, Misty Dawn Deboer, Eric C Maslowski, André Antonio Monteiro, Maurice Borges Vincent, Jon-Kar Zubieta, Alexandre F DaSilva

Abstract

Background: Although neuroimaging techniques have provided insights into the function of brain regions involved in Trigeminal Neuropathic Pain (TNP) in humans, there is little understanding of the molecular mechanisms affected during the course of this disorder. Understanding these processes is crucial to determine the systems involved in the development and persistence of TNP.

Findings: In this study, we examined the regional μ-opioid receptor (μOR) availability in vivo (non-displaceable binding potential BPND) of TNP patients with positron emission tomography (PET) using the μOR selective radioligand [11C]carfentanil. Four TNP patients and eight gender and age-matched healthy controls were examined with PET. Patients with TNP showed reduced μOR BPND in the left nucleus accumbens (NAc), an area known to be involved in pain modulation and reward/aversive behaviors. In addition, the μOR BPND in the NAc was negatively correlated with the McGill sensory and total pain ratings in the TNP patients.

Conclusions: Our findings give preliminary evidence that the clinical pain in TNP patients can be related to alterations in the endogenous μ-opioid system, rather than only to the peripheral pathology. The decreased availability of μORs found in TNP patients, and its inverse relationship to clinical pain levels, provide insights into the central mechanisms related to this condition. The results also expand our understanding about the impact of chronic pain on the limbic system.

Figures

Figure 1
Figure 1
Clinical profile of Trigeminal Neuropathic Pain patients recruited for this study (for more information, refer to the text). The pain location was accessed by a craniofacial pain map of the face [12]. This method (PainTrekW, University of Michigan) provides a 3D map of orofacial pain.
Figure 2
Figure 2
Changes in the μ-opioid receptor availability in Trigeminal Neuropathic Pain.A-C, Representation of decreased μOR BPND in the left NAc in axial (A), sagittal (B) and coronal (C) planes (T = 3.2). D, Plots of individual μOR BPND extracted from the left NAc. Each TNP patient is represented in a black circle and each healthy subject in a white circle. E, Correlations between MPQ scores (PRI and Sensory) and μOR BPND in the left NAc of TNP patients.

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