Comparison of Antiallodynic Effects between Intrathecal Cholinesterase Inhibitors and NMDA Antagonists on Two Neuropathic Pain Rat Models

Abstract

Cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) antagonists reduce the mechanical allodynia in neuropathic pain models. In this study our aim was to compare the antiallodynic effects between intrathecal cholinesterase inhibitors and NMDA antagonists on two well-characterized neuropathic pain rat models. Methods: Male Sprague Dawley rats were anesthetized and either had the left L5 and L6 spinal nerves ligated (SNL group) or Freund complete adjuvant (FCA) administrated to the sciatic nerve (FCA group) in order to cause neuropathic pain. A catheter was implanted into the intrathecal space for drug administration. After obtaining baseline values, edrophonium (3−100μg), neostigmine (0.3−10μg), AP-5 (0.3−3μg) and MK-801 (1−30μg) were administered intrathecally to each group. The allodynic left hind paw withdrawal thresholds to von Frey hairs were assessed and converted to % MPE. Antiallodynic effects on the two groups were compared by analyzing dose-response curves and ED 50 values. Motor weakness was also checked. Results: Intrathecal edrophonium, neostigmine, AP-5 and MK-801 had a dose-dependent antiallodynic effect on the two neuropathic pain models. Comparing the antiallodynic effect dose response curves, intrathecal cholinesterase inhibitors had lower ED 50 with steep slopes in the SNL model, whereas intrathecal NMDA antagonists had lower ED 50 in the FCA model, but there were no statistically significant differences between the two models. Conclusions: Intrathecal cholinesterase inhibitors and NMDA antagonists have relatively better antiallodynic effects on the SNL and FCA neuropathic pain rat models, respectively.