Abstract
Although depressive symptoms including anhedonia (i.e., loss of pleasure) frequently accompany pain, little is known about the risk factors contributing to individual differences in pain-induced anhedonia. In this study, we examined if signaling of brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin-receptor-kinase B (TrkB) contribute to individual differences in the development of neuropathic pain-induced anhedonia. Rats were randomly subjected to spared nerved ligation (SNI) or sham surgery. The SNI rats were divided into two groups based on the results of a sucrose preference test. Rats with anhedonia-like phenotype displayed lower tissue levels of BDNF in the medial prefrontal cortex (mPFC) compared with rats without anhedonia-like phenotype and sham-operated rats. In contrast, tissue levels of BDNF in the nucleus accumbens (NAc) of rats with an anhedonia-like phenotype were higher compared with those of rats without anhedonia-like phenotype and sham-operated rats. Furthermore, tissue levels of BDNF in the hippocampus, L2-5 spinal cord, muscle, and liver from both rats with or without anhedonia-like phenotype were lower compared with those of sham-operated rats. A single injection of 7,8-dihydroxyflavone (10 mg/kg; TrkB agonist), but not ANA-12 (0.5 mg/kg; TrkB antagonist), ameliorated reduced sucrose preference and reduced BDNF-TrkB signaling in the mPFC in the rats with anhedonia-like phenotype. These findings suggest that reduced BDNF-TrkB signaling in the mPFC might contribute to neuropathic pain-induced anhedonia, and that TrkB agonists could be potential therapeutic drugs for pain-induced anhedonia.