Reduced opioid receptors and anhedonia in chronic pain

Authors

• Scott J Thompson
• Mark H PItcher
• Laura Stone
• Farid Tarum
• Gang Niu
• Xiaoyuan Chen
• Dale O Kiesewetter
• Petra Schweinhardt
• M Catherine Bushnell

Abstract

Positron emission tomography (PET) shows reduced availability of brain opioid receptors in chronic pain patients. This could reflect increased receptor occupancy caused by ongoing pain, a reduction in the number of opioid receptors, or reduced neuronal matter. We investigated these possibilities using the spared nerve injury (SNI) rodent model of neuropathic pain. Using [18F]-diprenorphine PET (SNI n=17, sham n=17), we confirmed reduced opioid receptor availability in insula, caudate-putamen and motor cortex of SNI rats three-months post-surgery. Immunohistochemistry showed reduced expression of the mu-opioid receptor, MOR1, in caudate-putamen and insula. Neither the opioid peptide enkephalin nor the neuronal marker NeuN differed between groups. In nerve-injured animals, sucrose preference, a measure of anhedonia/depression, positively correlated with PET opioid receptor availability and MOR1 expression in the caudate-putamen. These findings provide new evidence that chronic pain alters the brain opioid system, which might explain the limited effectiveness of opioid therapy in chronic pain patients and contribute to pain-induced depression.

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