Gabapentin normalizes spinal neuronal responses that correlate with behavior in a rat model of cancer-induced bone pain

• Published in: Anesthesiology (Philadelphia) 2005, Vol.102 (1), p.132-140
• Main Authors: DONOVAN-RODRIGUEZ, Tansy, DICKENSON, Anthony H, URCH, Catherine E
• Format: Article
• Language: English
• Subjects: Amines - pharmacology; Analgesics - pharmacology; Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Behavior, Animal - drug effects; Behavior, Animal - physiology; Biological and medical sciences; Bone Neoplasms - complications; Cell Line, Tumor; Cyclohexanecarboxylic Acids - pharmacology; Dose-Response Relationship, Drug; Electric Stimulation; Electrophysiology; Evoked Potentials - drug effects; Gabapentin; gamma-Aminobutyric Acid - pharmacology; Male; Medical sciences; Neoplasm Transplantation; Neurons - drug effects; Osteotomy; Pain - etiology; Pain - physiopathology; Pain - psychology; Pain Measurement - drug effects; Physical Stimulation; Rats; Rats, Sprague-Dawley; Spinal Cord - cytology; Spinal Cord - drug effects; Temperature
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/00000542-200501000-00022

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.