Proceedings of The Physiological Society
University of Cambridge (2008) Proc Physiol Soc 11, PC101
The role of glutamate receptor ligands in allodynia, hypersensitivity and morphine analgesia during neuropathic pain in mice.
M. Osikowicz1, J. Mika1, W. Makuch1, B. Przewlocka1
1. Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
Recent evidence have indicated that metabotropic glutamate receptor (mGluR) type 5, 2/3 and 7 are present in regions of central nervous system important for nociceptive transmission [2-4], but their involvement in neuropathic pain has not been well established. The present study was aimed to exam the influences of mGluR5 antagonist: MPEP, mGluR2/3 agonist: LY379268 and mGluR7 agonist: AMN082 on development of neuropathic pain symptoms and on morphine effects in Albino Swiss mice after sciatic nerve injury. Chronic constriction injury (CCI) to the sciatic nerve was performed under pentobarbital (36 mg/kg; I.P.) anaesthesia using the procedure described by Bennett and Xie . The mechanical allodynia (von Frey test) was performed in order to evaluate sensitivity to mechanical stimulus. The cold plate test was used to assess sensitivity to cold stimulus. The experimental procedures were performed according to the Institute’s Animal Research Bioethics Committee and in accordance with the NIH Guide for the Care and Use of Laboratory Animals. The data were calculated as the mean ± SEM or as a percent of maximal possible effect (%MPE) ± SEM (n=8-12 per group). Our results demonstrated that both acute and chronic administration of MPEP, LY379268, and AMN082 attenuated allodynia and hyperalgesia seven days after CCI in mice. Moreover, single administration of MPEP (30 mg/kg; I.P.) or LY379268 (10 mg/kg; I.P.) injected 30 min before morphine (20 mg/kg; I.P.) potentiated morphine analgesic effect towards mechanical allodynia and thermal hyperalgesia in the mouse CCI model. Whereas, a single administration of AMN082 (3 mg/kg; I.P.) potentiated the effects of a single morphine injection (20 mg/kg; I.P.) only in the von Frey test. Chronic administration (for seven days) of low doses of MPEP, LY379268 or AMN082 (all drugs at 3 mg/kg; I.P.) potentiated the effects of single doses of morphine (3, 10, 20 mg/kg; I.P.) administered on the last day of experiment; however, AMN082 potentiated only the effect in the cold plate test. Additionally, the same doses of MPEP and LY379268 (but not AMN082) chronically co-administered with morphine (40 mg/kg; I.P.) attenuated the development of morphine tolerance in CCI-exposed mice [5, in press, PAIN]. Our data suggests that mGluR5, mGluR2/3, and mGluR7 are involved in injury-induced plastic changes in nociceptive pathways and that mGluR5 and mGluR2/3 ligands enhanced morphine’s effectiveness in neuropathy, which could have therapeutic implications.
Where applicable, experiments conform with Society ethical requirements