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Spinal AMPA receptor inhibition attenuates mechanical allodynia and neuronal hyperexcitability following spinal cord injury in rats.
J Neurosci Res. 2007 Aug 15; 85(11):2352-9.JN

Abstract

In this study, we examined whether a competitive AMPA receptor antagonist, NBQX, attenuates mechanical allodynia and hyperexcitability of spinal neurons in remote, caudal regions in persistent central neuropathic pain following spinal cord injury in rats. Spinal cord injury was produced by unilateral T13 transverse spinal hemisection, from dorsal to ventral, in male Sprague Dawley rats (200-250 g). Mechanical thresholds were measured behaviorally, and the excitability of wide-dynamic-range (WDR) dorsal horn neurons in the lumbar cord (L4-L5) was measured to assess central neuropathicpain. On postoperation day (POD) 28 after spinalhemisection, mechanical thresholds were significantly decreased in both injured (ipsilateral) and noninjured (contralateral) hindpaws compared with preinjury and sham control, respectively (P < 0.05). Intrathecal administration of NBQX (0.25, 0.5, 1 mM) significantly reversed the decreased mechanical thresholds in both hindpaws, dose dependently (P < 0.05). The excitability of WDR neurons was significantly enhanced on both sides of the lumbar dorsal horn 28 days following spinal hemisection (P < 0.05). The hyperexcitability of WDR neurons was attenuated by topical administration of NBQX (0.125, 0.25, 0.5, 1 mM), dose dependently (P < 0.05). Regression analysis indicated that at least three molecules of NBQX bond per receptor complex, and are needed to achieve inhibition of WDR hyperexcitability. In conclusion, our study demonstrates that the AMPA receptor plays an important role in behaviors related to the maintenance of central neuropathic pain below the level of spinal cord injury.

Authors+Show Affiliations

Department of Physiology, Brain Research Institute, and BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. ysgwak@utmb.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17549753

Citation

Gwak, Young Seob, et al. "Spinal AMPA Receptor Inhibition Attenuates Mechanical Allodynia and Neuronal Hyperexcitability Following Spinal Cord Injury in Rats." Journal of Neuroscience Research, vol. 85, no. 11, 2007, pp. 2352-9.
Gwak YS, Kang J, Leem JW, et al. Spinal AMPA receptor inhibition attenuates mechanical allodynia and neuronal hyperexcitability following spinal cord injury in rats. J Neurosci Res. 2007;85(11):2352-9.
Gwak, Y. S., Kang, J., Leem, J. W., & Hulsebosch, C. E. (2007). Spinal AMPA receptor inhibition attenuates mechanical allodynia and neuronal hyperexcitability following spinal cord injury in rats. Journal of Neuroscience Research, 85(11), 2352-9.
Gwak YS, et al. Spinal AMPA Receptor Inhibition Attenuates Mechanical Allodynia and Neuronal Hyperexcitability Following Spinal Cord Injury in Rats. J Neurosci Res. 2007 Aug 15;85(11):2352-9. PubMed PMID: 17549753.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spinal AMPA receptor inhibition attenuates mechanical allodynia and neuronal hyperexcitability following spinal cord injury in rats. AU - Gwak,Young Seob, AU - Kang,Jonghoon, AU - Leem,Joong Woo, AU - Hulsebosch,Claire E, PY - 2007/6/6/pubmed PY - 2007/12/13/medline PY - 2007/6/6/entrez SP - 2352 EP - 9 JF - Journal of neuroscience research JO - J Neurosci Res VL - 85 IS - 11 N2 - In this study, we examined whether a competitive AMPA receptor antagonist, NBQX, attenuates mechanical allodynia and hyperexcitability of spinal neurons in remote, caudal regions in persistent central neuropathic pain following spinal cord injury in rats. Spinal cord injury was produced by unilateral T13 transverse spinal hemisection, from dorsal to ventral, in male Sprague Dawley rats (200-250 g). Mechanical thresholds were measured behaviorally, and the excitability of wide-dynamic-range (WDR) dorsal horn neurons in the lumbar cord (L4-L5) was measured to assess central neuropathicpain. On postoperation day (POD) 28 after spinalhemisection, mechanical thresholds were significantly decreased in both injured (ipsilateral) and noninjured (contralateral) hindpaws compared with preinjury and sham control, respectively (P < 0.05). Intrathecal administration of NBQX (0.25, 0.5, 1 mM) significantly reversed the decreased mechanical thresholds in both hindpaws, dose dependently (P < 0.05). The excitability of WDR neurons was significantly enhanced on both sides of the lumbar dorsal horn 28 days following spinal hemisection (P < 0.05). The hyperexcitability of WDR neurons was attenuated by topical administration of NBQX (0.125, 0.25, 0.5, 1 mM), dose dependently (P < 0.05). Regression analysis indicated that at least three molecules of NBQX bond per receptor complex, and are needed to achieve inhibition of WDR hyperexcitability. In conclusion, our study demonstrates that the AMPA receptor plays an important role in behaviors related to the maintenance of central neuropathic pain below the level of spinal cord injury. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/17549753/Spinal_AMPA_receptor_inhibition_attenuates_mechanical_allodynia_and_neuronal_hyperexcitability_following_spinal_cord_injury_in_rats_ L2 - https://doi.org/10.1002/jnr.21379 DB - PRIME DP - Unbound Medicine ER -