ASSESSING THE OUTCOME OF PERIPHERAL NERVE INJURY IN A RODENT MODEL: BEHAVIORAL, PHARMACOLOGICAL, IMMUNOHISTOCHEMICAL, AND MASS-SPECTROMETRIC STUDIES

Abstract

Chronic neuropathic pain (CNP) is a pathophysiological condition and is pain that lasts for longer than 3 months. CNP is usually the result of injury or disease to the central nervous system (CNS) or the peripheral nervous system (PNS). Despite their reputation and their possible side effects, opioids remain a main treatment option for CNP. Preclinical work from the lab has previously shown that an injury to the CNS, in the form of spinal cord injury (SCI), led to CNP in the rat model, and additional data showed that treatment with opioids had an analgesic effect in only ~ 1/3 of the animals tested. SCI is a massive injury inflicted onto the CNS, and here we wanted to probe the outcome of a less severe injury to the PNS, sciatic nerve ligation (SNL) on the development of pain and chronic pain. The aims of this project were to a) determine the behavioral outcome of SNL on pain behaviors, b) assess the analgesic effects of morphine treatment after SNL, c) probe for morphine and dopamine receptor expression in the dorsal root ganglia (DRGs) that receive the sensory information from the periphery, and d) test if the injury potentially led to systemwide changes that could be detected in the blood proteome. We found that, as in centrally-induced pain models, SNL led to a decrease in pain reflex latencies, indicative of a heightened pain sensitivity. Treatment with morphine was also only effective in less than 40% of the animals, again similar to the CNS model. In addition, we found that morphine mu-receptors (MORs) were upregulated in ipsilateral over contralateral dorsal root ganglia (DRGs) at the level of the injury. In contrast, we did not find differences in dopamine D1 receptor (D1R) expression between ipsi- and contralateral sides. Blood samples collected prior to and following SNL were processed for unbiased proteomics. Proteomic analysis identified that unilateral SNL altered the blood proteomic profile. Together, these data suggest that the peripherally-induced unilateral injury mimics the outcomes of the centrally induced CNP model, and that it leads to chronic pain-manifestations that affect both specific neural tissues and blood proteome alike.