Gabapentin Normalizes Spinal Neuronal Responses That Correlate with Behavior in a Rat Model of Cancer-induced Bone Pain

Abstract

Cancer-induced bone pain is a major clinical problem for which current treatments lack full efficacy. Gabapentin is licensed for use in neuropathic pain yet is also effective against inflammatory stimuli in animals. A rat model of cancer-induced bone pain using the MRMT-1 cell line injected into the tibia was established to investigate the efficacy of acute (10, 30, 100 mg/kg) and chronic (30 mg/kg) systemic gabapentin on electrophysiological superficial dorsal horn neuronal responses to natural and noxious electrical stimuli, as well as on pain-related behavior. In electrophysiological studies gabapentin worked both acutely (100 mg/kg) and chronically (30 mg/kg) to normalize the hyperexcitable superficial dorsal horn neuronal response, significantly reducing electrical-evoked and mechanical-evoked but not thermal-evoked responses. The behavioral study showed that chronic gabapentin (30 mg/kg) significantly attenuated pain behavior in MRMT-1 rats, restoring responses to preoperative baseline degrees, and that this attenuation was accompanied by a reversion to normal (non-MRMT-1) wide-dynamic-range: nociceptive specific superficial dorsal horn neuronal profiles. Pain-related behavior in this rat model of cancer-induced bone pain is strongly linked to hyperexcitability of a population of superficial dorsal horn neurones. Gabapentin normalizes the cancer-induced bone pain induced dorsal horn neuronal changes and attenuates pain behavior. It may therefore provide a novel clinical treatment for cancer-induced bone pain.