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Effects of GABA receptor antagonist on trigeminal caudalis nociceptive neurons in normal and neonatally capsaicin-treated rats.
J Neurophysiol. 1999 Nov; 82(5):2154-62.JN

Abstract

We have recently demonstrated that significant increases in cutaneous mechanoreceptive field (RF) size and spontaneous activity occur in nociceptive neurons of trigeminal subnucleus caudalis (Vc, the medullary dorsal horn) of adult rats depleted of C-fiber afferents by neonatal treatment with capsaicin. These neuronal changes in capsaicin-treated (CAP) rats are suggestive of central neuroplasticity and involve N-methyl-D-aspartic acid (NMDA) receptor mechanisms. The present study examined whether the GABA(A) receptor antagonist bicuculline (BIC) or the GABA(B) receptor antagonist 2-hydroxysaclofen (SAC) can influence the RF properties and activity of Vc nociceptive neurons classified as either nociceptive-specific or wide-dynamic range in CAP adult rats or in neonatally vehicle-treated (CON) rats. C-fiber depletion was confirmed in the CAP rats by a significant decrease in plasma extravasation of Evans blue dye in a skin area receiving topical application of mustard oil, a small-fiber excitant and inflammatory irritant. As previously reported, marked increases in cutaneous RF size and spontaneous activity occurred in Vc nociceptive neurons of adult CAP rats, compared with CON rats. GABA(A) receptor blockade by BIC (i.t.) in CON rats produced a significant increase in spontaneous activity and in pinch RF size and tactile RF size (or appearance of a tactile area in the RF of nociceptive-specific neurons), as well as a significant lowering of the mechanical threshold and a significant enhancement of responses to pinch stimuli applied to the RF. In CAP rats, GABA(A) receptor blockade also produced significant changes similar to those documented in CON rats, except for a paradoxical and significant decrease in pinch RF size and no noticeable changes in responses to pinch stimuli. GABA(B) receptor blockade by SAC (i.t.) did not produce any significant changes in Vc nociceptive neurons in either CON or CAP rats. These results suggest that GABA(A) receptor-mediated inhibition may be involved in maintaining the functional expression of Vc nociceptive neuronal properties in normal conditions, and that in animals depleted of their C-fiber afferents, some features of this GABA(A) receptor-mediated modulation may be disrupted such that a GABA(A) receptor-mediated excitation is manifested.

Authors+Show Affiliations

Faculty of Dentistry, University of Toronto, Toronto, Ontario M5G 1G6, Canada.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

10561395

Citation

Chiang, C Y., et al. "Effects of GABA Receptor Antagonist On Trigeminal Caudalis Nociceptive Neurons in Normal and Neonatally Capsaicin-treated Rats." Journal of Neurophysiology, vol. 82, no. 5, 1999, pp. 2154-62.
Chiang CY, Kwan CL, Hu JW, et al. Effects of GABA receptor antagonist on trigeminal caudalis nociceptive neurons in normal and neonatally capsaicin-treated rats. J Neurophysiol. 1999;82(5):2154-62.
Chiang, C. Y., Kwan, C. L., Hu, J. W., & Sessle, B. J. (1999). Effects of GABA receptor antagonist on trigeminal caudalis nociceptive neurons in normal and neonatally capsaicin-treated rats. Journal of Neurophysiology, 82(5), 2154-62.
Chiang CY, et al. Effects of GABA Receptor Antagonist On Trigeminal Caudalis Nociceptive Neurons in Normal and Neonatally Capsaicin-treated Rats. J Neurophysiol. 1999;82(5):2154-62. PubMed PMID: 10561395.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of GABA receptor antagonist on trigeminal caudalis nociceptive neurons in normal and neonatally capsaicin-treated rats. AU - Chiang,C Y, AU - Kwan,C L, AU - Hu,J W, AU - Sessle,B J, PY - 1999/11/24/pubmed PY - 1999/11/24/medline PY - 1999/11/24/entrez SP - 2154 EP - 62 JF - Journal of neurophysiology JO - J. Neurophysiol. VL - 82 IS - 5 N2 - We have recently demonstrated that significant increases in cutaneous mechanoreceptive field (RF) size and spontaneous activity occur in nociceptive neurons of trigeminal subnucleus caudalis (Vc, the medullary dorsal horn) of adult rats depleted of C-fiber afferents by neonatal treatment with capsaicin. These neuronal changes in capsaicin-treated (CAP) rats are suggestive of central neuroplasticity and involve N-methyl-D-aspartic acid (NMDA) receptor mechanisms. The present study examined whether the GABA(A) receptor antagonist bicuculline (BIC) or the GABA(B) receptor antagonist 2-hydroxysaclofen (SAC) can influence the RF properties and activity of Vc nociceptive neurons classified as either nociceptive-specific or wide-dynamic range in CAP adult rats or in neonatally vehicle-treated (CON) rats. C-fiber depletion was confirmed in the CAP rats by a significant decrease in plasma extravasation of Evans blue dye in a skin area receiving topical application of mustard oil, a small-fiber excitant and inflammatory irritant. As previously reported, marked increases in cutaneous RF size and spontaneous activity occurred in Vc nociceptive neurons of adult CAP rats, compared with CON rats. GABA(A) receptor blockade by BIC (i.t.) in CON rats produced a significant increase in spontaneous activity and in pinch RF size and tactile RF size (or appearance of a tactile area in the RF of nociceptive-specific neurons), as well as a significant lowering of the mechanical threshold and a significant enhancement of responses to pinch stimuli applied to the RF. In CAP rats, GABA(A) receptor blockade also produced significant changes similar to those documented in CON rats, except for a paradoxical and significant decrease in pinch RF size and no noticeable changes in responses to pinch stimuli. GABA(B) receptor blockade by SAC (i.t.) did not produce any significant changes in Vc nociceptive neurons in either CON or CAP rats. These results suggest that GABA(A) receptor-mediated inhibition may be involved in maintaining the functional expression of Vc nociceptive neuronal properties in normal conditions, and that in animals depleted of their C-fiber afferents, some features of this GABA(A) receptor-mediated modulation may be disrupted such that a GABA(A) receptor-mediated excitation is manifested. SN - 0022-3077 UR - https://www.unboundmedicine.com/medline/citation/10561395/Effects_of_GABA_receptor_antagonist_on_trigeminal_caudalis_nociceptive_neurons_in_normal_and_neonatally_capsaicin_treated_rats_ L2 - http://www.physiology.org/doi/full/10.1152/jn.1999.82.5.2154?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -