Effect of systemic and intrathecal gabapentin on allodynia in a new rat model of postherpetic neuralgia.
Patients with postherpetic neuralgia often have an increased sensitivity to a tactile stimulus but impaired thermal sensitivity in the same affected dermatomes. We recently found that depletion of capsaicin-sensitive afferents by systemic treatment with a potent TRPV1 agonist, resiniferotoxin, in adult rats produces long-lasting paradoxical changes in mechanical and thermal sensitivities, which resemble the unique clinical features of postherpetic neuralgia. The anticonvulsant gabapentin is effective in reducing the subjective pain score in patients with postherpetic neuralgia. In this study, we quantified the potential effect of systemic and intrathecal gabapentin on tactile allodynia induced by resiniferotoxin in rats. Intraperitoneal injection of 200 microg/kg resiniferotoxin produced a rapid and sustained increase in the paw withdrawal latency to a radiant heat stimulus. Profound tactile allodynia developed in all the resiniferotoxin-treated rats within 3 weeks. Intraperitoneal injection of 30-60 mg/kg of gabapentin in resiniferotoxin-treated rats significantly increased the withdrawal threshold in response to von Frey filaments. Furthermore, intrathecal administration of 10-30 microg of gabapentin also produced a significant effect on the mechanical withdrawal threshold in all resiniferotoxin-treated rats. These data provide complementary new information that gabapentin administered systemically and spinally can effectively relieve tactile allodynia in this animal model of postherpetic neuralgia.
Chen
Shao-Rui
SR
Department of Anesthesiology, Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
Pan
Hui-Lin
HL
D000588:Amines / Q000008:administration & dosage*; D000700:Analgesics / Q000008:administration & dosage*; D000818:Animals; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004224:Diterpenes; D000077206:Gabapentin; D006358:Hot Temperature; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects; D009437:Neuralgia / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D009619:Nociceptors / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014110:Touch / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage*
D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D004224:Diterpenes; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; C024353:resiniferatoxin