Background: Transmission of pain in spinal cord to brain requires N-methyl-D-aspartate receptor (NMDAR) activity to transmit glutamatergic signaling between neurons. NMDAR activity is decreased due to opiates activating the mu-opioid receptor (MOR) in the short term. In the long term, a tolerance to this effect develops, which is a major contributor to dose escalation and subsequently the abuse of opiates. Cross-talk between MOR and NMDAR is mediated by HINT1. HINT1 has not been studied in neuropathic pain states, a prolonged state of pain in which several mechanisms lead to continuous activity of NMDAR and thus the perception of pain. Depending on the role of HINT1 in neuropathic pain, HINT1 may be a promising target for alternatives to opiates in the treatment of pain. 

Methods: Immunohistochemistry, spared nerve injury, intrathecal injection, confocal imaging, Von Frey mechanical hypersensitivity threshold, rotarod

Results/Conclusions: While further testing is required, initial results indicate no significant increase of HINT1 expression in lumbar segment 3 DRG ipsilateral to nerve injury; this segment innervates the area of induced chronic pain. We also observed a significant decrease in the behavioral manifestation of hypersensitivity when mice were intrathecally injected with HINT1 inhibitors.