INTRODUCTION: Neuropathic pain is difficult to control. Morphine produces strong analgesic effects, but with several side effects. Endogenous opioids are clinically safe, but are not used for treatment due to rapid metabolism. However, in vivo transfection of endogenous opioid genes could produce a safe yet powerful analgesic effect. Proopiomelanocortin (POMC) is the precursor for β‐endorphin, an endogenous opioid. This study investigated the analgesic effects of POMC gene transfection using radial shock waves (RSWs) in a rat neuropathic pain model.
METHODS: Chronic constriction injury (CCI) was used to induce neuropathic pain. Rats were divided into three groups: CCI group (n=15), CCI+POMC group (n=15), and control group (n=15). Rats were injected with 100μg POMC gene into their left gastrocnemius muscle before exposure to RSWs. Mechanical allodynia was measured over four weeks. The left gastrocnemius was resected and immunostained for β‐endorphin. Blood was sampled from the heart, and blood β‐endorphin concentrations were assayed using ELISA. In some rats, L4/L5 dorsal root ganglia (DRG) were harvested, sectioned, and immunostained for calcitonin gene‐related peptide (CGRP, a pain‐related neuropeptide) 4, 7, and 14 days post‐surgery. We also evaluated side effects, including body weight and changes in food and water intake.
RESULTS: β‐endorphin blood levels and number of β‐endorphin‐immunoreactive (‐IR) muscle fibers increased significantly in the CCI+POMC group (p<0.01). Compared to the control group, allodynia developed in the CCI group (p<0.05) and CGRP‐IR neurons were increased (p<0.01). However, POMC gene transfection significantly reduced both allodynia and CGRP expression (p<0.05). There were no significant differences in side effects among the groups.
DISCUSSION: POMC gene transfection alleviated allodynia and reduced CGRP expression. These results suggest that POMC gene transfection using RSW is a safe and effective treatment for neuropathic pain.