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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Donovan-Rodriguez
Tansy
T
Department of Pharmacology, University College London, London, United Kingdom.
Dickenson
Anthony H
AH
Urch
Catherine E
CE
D000588:Amines / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology*; D001859:Bone Neoplasms / Q000150:complications*; D045744:Cell Line, Tumor; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004594:Electrophysiology; D005071:Evoked Potentials / Q000187:drug effects; D000077206:Gabapentin; D008297:Male; D009368:Neoplasm Transplantation; D009474:Neurons / Q000187:drug effects*; D010027:Osteotomy; D010146:Pain / Q000209:etiology / Q000503:physiopathology / Q000523:psychology*; D010147:Pain Measurement / Q000187:drug effects; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects*; D013696:Temperature; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin