Journal of Neurophysiology, Vol 68, Issue 2 392-396, Copyright © 1992 by APS

ARTICLES

Baclofen reverses the hypersensitivity of dorsal horn wide dynamic range neurons to mechanical stimulation after transient spinal cord ischemia; implications for a tonic GABAergic inhibitory control of myelinated fiber input

J. X. Hao, X. J. Xu, Y. X. Yu, A. Seiger and Z. Wiesenfeld-Hallin
Department of Clinical Physiology, Karolinska Institute, Huddinge University Hospital, Sweden.

1. In the companion paper, we described a state of hypersensitivity that developed in dorsal horn wide dynamic range (WDR) neurons in rats after transient spinal cord ischemia. Thus the WDR neurons exhibited lower threshold and increased responses to low-intensity mechanical stimuli. The response pattern of these neurons to suprathreshold electrical stimulation was also changed. Notably, the response to A-fiber input was increased. No change in response to thermal stimulation was found before and after spinal cord ischemia. 2. In normal rats, the gamma-aminobutyric acid (GABA)B agonist baclofen (0.1 mg/kg ip) administered 1-3 h before neuronal recording suppressed the responses of WDR neurons to high-intensity mechanical pressure without influencing the threshold and the responses to lower-intensity stimuli. 3. In allodynic rats, similar pretreatment with baclofen totally reversed the hypersensitivity of the WDR neurons to mechanical stimuli and normalized the response pattern of neurons to electrical stimulation. 4. The GABAA receptor agonist muscimol (1 mg/kg ip) did not influence the response of WDR neurons in either normal or allodynic animals. 5. The present results demonstrated that the GABAB agonist baclofen is effective in reversing the hypersensitivity of dorsal horn WDR neurons to low-intensity mechanical stimulation after transient spinal cord ischemia, indicating that dysfunction of the GABAergic inhibitory system may be responsible for the development of neuronal hypersensitivity. 6. It is suggested that GABAergic interneurons exert a tonic presynaptic inhibitory control, through baclofen-sensitive B-type GABA receptors, on input from low-threshold mechanical afferents, and that disruption of this control may result in painful reaction to innocuous stimuli (allodynia).

This article has been cited by other articles:

				K. J. Dougherty and S. Hochman Spinal Cord Injury Causes Plasticity in a Subpopulation of Lamina I GABAergic Interneurons J Neurophysiol, July 1, 2008; 100(1): 212 - 223. [Abstract] [Full Text] [PDF]

				J.-X. Hao, R. C. Kupers, and X.-J. Xu Response Characteristics of Spinal Cord Dorsal Horn Neurons in Chronic Allodynic Rats After Spinal Cord Injury J Neurophysiol, September 1, 2004; 92(3): 1391 - 1399. [Abstract] [Full Text] [PDF]

				K. J. Hutchinson, F. Gomez-Pinilla, M. J. Crowe, Z. Ying, and D. M. Basso Three exercise paradigms differentially improve sensory recovery after spinal cord contusion in rats Brain, June 1, 2004; 127(6): 1403 - 1414. [Abstract] [Full Text] [PDF]

				E. Parisod, P. J. Siddall, M. Viney, J. M. McClelland, and M. J. Cousins Allodynia After Acute Intrathecal Morphine Administration in a Patient with Neuropathic Pain After Spinal Cord Injury Anesth. Analg., July 1, 2003; 97(1): 183 - 186. [Abstract] [Full Text] [PDF]

				K. Madden, W. Clark, and N. Lessov Failure of Ischemic Neuroprotection by Potentiators of Gamma-aminobutyric Acid Clin. Med. Res., April 1, 2003; 1(2): 119 - 124. [Abstract] [Full Text] [PDF]

				R. Gade-Andavolu, J. P. MacMurray, H. Blake, D. Muhleman, W. Tourtellotte, and D. E. Comings Association Between the {gamma}-Aminobutyric Acid A3 Receptor Gene and Multiple Sclerosis Arch Neurol, April 1, 1998; 55(4): 513 - 516. [Abstract] [Full Text] [PDF]

				A. J. Reeve, A. H. Dickenson, and N. C. Kerr Spinal Effects of Bicuculline: Modulation of an Allodynia-Like State by an A1-Receptor Agonist, Morphine, and an NMDA-Receptor Antagonist J Neurophysiol, March 1, 1998; 79(3): 1494 - 1507. [Abstract] [Full Text] [PDF]