Effects of Pre-treatment with NMDA Antagonist for Tactile Allodynia in Nerve Ligation Induced Neuropathic Pain Rat

Lee, Youn Woo; Yoon, Duck Mi; Lee, Jong Seok; Ahn, Eun Kyoung; Lee, Young Sook; Kim, Jong Rae

Abstract

BACKGROUND: Following peripheral nerve injury, rats will show a tactile allodynia and hyperalgesia. But the mechanism of allodynia is still obscure. Previous studies have shown this allodynia was reversed by intrathecal alpha-2 agonists and NMDA antagonists, but not by morphine. In formalin test, either the pretreatment of NMDA antagonist or morphine prevents the hyperalgesia. The present studies, using rats rendered allodynic by ligation of the left L5 and L6 nerves, aimed to investigate the effects of pretreatment of MK-80l and morphine on the development of tactile allodynia.
METHODS
AND MATERIAL: Male Sprague-Dawley rats (100-150 g) were anesthetized with halothane, the left L5 and L6 spinal nerves were ligated tightly by 6-0 black silk. For sham operation muscle dissection was performed but the spinal nerve was not ligated. For pretreatment of drugs, MK-801 (NMDA antagonist; 0.3mg/kg). CNQX (non-NMDA antagonist; 0.3mg/kg), morphine (1 mg/kg) or saline (placebo) was administered subcutaneously 30 minutes before operation. A second dose was administered subcutaneously 24 hours after operation and further doses were given daily for 2 days further. The volume of injection was 5 ml/kg. To assess the mechanical allodynia, paw withdrawal thresholds of ipsilateral limb were determined using 8 von Frey hairs.
RESULTS
Within 2 days saline, CNQX or morphine injected rats developed tactile allodynia (paw withdrawal threshold was about 2 g), and persisted for over 2 weeks. Pretreatment of MK-801 delayed the development of tactile allodynia for 3 days comparing to that of saline injected rat.
CONCLUSION
NMDA receptor in the central nerve system plays an important role in the development of tactile allodynia induced by peripheral nerve injury. But the mechanism may be different from hyperalgesia developed in formalin test.