Reduced opioid receptors and anhedonia in chronic pain

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.