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Synergistic effect between intrathecal non-NMDA antagonist and gabapentin on allodynia induced by spinal nerve ligation in rats.
Anesthesiology. 2000 Feb; 92(2):500-6.A

Abstract

BACKGROUND

Glutamate and non-N-methyl-D-aspartate (NMDA) receptors have been implicated in the development of neuroplasticity in the spinal cord in neuropathic pain. The spinal cord has been identified as one of the sites of the analgesic action of gabapentin. In the current study, the authors determined the antiallodynic effect of intrathecal 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in a rat model of neuropathic pain. Also tested was a hypothesis that intrathecal injection of CNQX and gabapentin produces a synergistic effect on allodynia in neuropathic rats.

METHODS

Allodynia was produced in rats by ligation of the left L5 and L6 spinal nerves. Allodynia was determined by application of von Frey filaments to the left hind paw. Through an implanted intrathecal catheter, 10-100 microg gabapentin or 0.5-8 microg CNQX disodium (a water-soluble formulation of CNQX) was injected in conscious rats. Isobolographic analysis was performed comparing the interaction of intrathecal gabapentin and CNQX using the ED50 dose ratio of 15:1.

RESULTS

Intrathecal treatment with gabapentin or CNQX produced a dose-dependent increase in the withdrawal threshold to mechanical stimulation. The ED50 for gabapentin and CNQX was 45.9+/-4.65 and 3.4+/-0.22 microg, respectively. Intrathecal injection of a combination of CNQX and gabapentin produced a strong synergistic antiallodynic effect in neuropathic rats.

CONCLUSIONS

This study shows that intrathecal administration of CNQX exhibits an antiallodynic effect in this rat model of neuropathic pain. Furthermore, CNQX and gabapentin, when combined intrathecally, produce a potent synergistic antiallodynic effect on neuropathic pain in spinal nerve-ligated rats.

Authors+Show Affiliations

Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1009, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10691238

Citation

Chen, S R., et al. "Synergistic Effect Between Intrathecal non-NMDA Antagonist and Gabapentin On Allodynia Induced By Spinal Nerve Ligation in Rats." Anesthesiology, vol. 92, no. 2, 2000, pp. 500-6.
Chen SR, Eisenach JC, McCaslin PP, et al. Synergistic effect between intrathecal non-NMDA antagonist and gabapentin on allodynia induced by spinal nerve ligation in rats. Anesthesiology. 2000;92(2):500-6.
Chen, S. R., Eisenach, J. C., McCaslin, P. P., & Pan, H. L. (2000). Synergistic effect between intrathecal non-NMDA antagonist and gabapentin on allodynia induced by spinal nerve ligation in rats. Anesthesiology, 92(2), 500-6.
Chen SR, et al. Synergistic Effect Between Intrathecal non-NMDA Antagonist and Gabapentin On Allodynia Induced By Spinal Nerve Ligation in Rats. Anesthesiology. 2000;92(2):500-6. PubMed PMID: 10691238.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synergistic effect between intrathecal non-NMDA antagonist and gabapentin on allodynia induced by spinal nerve ligation in rats. AU - Chen,S R, AU - Eisenach,J C, AU - McCaslin,P P, AU - Pan,H L, PY - 2000/2/26/pubmed PY - 2000/3/11/medline PY - 2000/2/26/entrez SP - 500 EP - 6 JF - Anesthesiology JO - Anesthesiology VL - 92 IS - 2 N2 - BACKGROUND: Glutamate and non-N-methyl-D-aspartate (NMDA) receptors have been implicated in the development of neuroplasticity in the spinal cord in neuropathic pain. The spinal cord has been identified as one of the sites of the analgesic action of gabapentin. In the current study, the authors determined the antiallodynic effect of intrathecal 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in a rat model of neuropathic pain. Also tested was a hypothesis that intrathecal injection of CNQX and gabapentin produces a synergistic effect on allodynia in neuropathic rats. METHODS: Allodynia was produced in rats by ligation of the left L5 and L6 spinal nerves. Allodynia was determined by application of von Frey filaments to the left hind paw. Through an implanted intrathecal catheter, 10-100 microg gabapentin or 0.5-8 microg CNQX disodium (a water-soluble formulation of CNQX) was injected in conscious rats. Isobolographic analysis was performed comparing the interaction of intrathecal gabapentin and CNQX using the ED50 dose ratio of 15:1. RESULTS: Intrathecal treatment with gabapentin or CNQX produced a dose-dependent increase in the withdrawal threshold to mechanical stimulation. The ED50 for gabapentin and CNQX was 45.9+/-4.65 and 3.4+/-0.22 microg, respectively. Intrathecal injection of a combination of CNQX and gabapentin produced a strong synergistic antiallodynic effect in neuropathic rats. CONCLUSIONS: This study shows that intrathecal administration of CNQX exhibits an antiallodynic effect in this rat model of neuropathic pain. Furthermore, CNQX and gabapentin, when combined intrathecally, produce a potent synergistic antiallodynic effect on neuropathic pain in spinal nerve-ligated rats. SN - 0003-3022 UR - https://www.unboundmedicine.com/medline/citation/10691238/Synergistic_effect_between_intrathecal_non_NMDA_antagonist_and_gabapentin_on_allodynia_induced_by_spinal_nerve_ligation_in_rats_ L2 - https://pubs.asahq.org/anesthesiology/article-lookup/doi/10.1097/00000542-200002000-00033 DB - PRIME DP - Unbound Medicine ER -