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Kainate-induced excitation and sensitization of nociceptors in normal and inflamed rat glabrous skin.
Neuroscience. 2006 Feb; 137(3):999-1013.N

Abstract

This study investigates contributions of peripheral kainate receptors to acute nociception and persistent inflammatory pain in rat. Immunohistochemical analysis of kainate receptor expression using antibodies recognizing glutamate receptor subunits 5, 6, and 7 demonstrates that 28% of unmyelinated axons in normal digital nerve are positively labeled. Following intraplantar injection of complete Freund's adjuvant, a significant increase in glutamate receptor subunits 5, 6, and 7-labeled axons occurs at 2 days (40%), but not 7 (31%) or 14 days (28%) post-complete Freund's adjuvant. In behavioral studies, we confirm an increased mechanical sensitivity in complete Freund's adjuvant-injected hind paws. Furthermore, activation of kainate receptors following intraplantar injection of 1.0 mM kainate in normal animals results in a mechanical sensitivity similar to that observed in inflamed animals. A 1.0 mM kainate injection into inflamed hind paws further enhances the mechanical sensitivity. Injection of the non-N-methyl-D-aspartate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (0.1 mM) reverses complete Freund's adjuvant-induced mechanical sensitivity through a local effect. In single unit recordings from nociceptors in a glabrous skin-nerve preparation, mechanical sensitization is present in inflamed skin evidenced by a decrease in mechanical threshold and an increase in discharge rate during a suprathreshold, constant force stimulus. Thermal sensitization is also present evidenced by a decrease in heat threshold. There is a dose-dependent increase in kainate-induced nociceptor activity in both normal and inflamed skin but the kainate required to induce activation is reduced in inflamed skin. Although proportions of kainate-activated nociceptors are the same in normal and inflamed skin, the kainate-induced mean discharge rate is significantly enhanced in inflamed skin. Exposure of normal and inflamed nociceptors to 0.3 mM kainate sensitizes fibers to re-application of kainate and heat. This sensitization is blocked in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione or the glutamate receptor subunit 5 selective antagonist 3S,4aR,6S,8aR-6-[4-carboxy-phenyl] methyl-1,2,3,4,4a,5,6,7,8,8a-deca-hydroisoquinoline-3-carboxylic acid. The data indicate that peripheral kainate receptors not only play an important role in normal nociception but also contribute to mechanical sensitivity and heat sensitization accompanying inflammatory pain.

Authors+Show Affiliations

Department of Neuroscience and Cell Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1069, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16330152

Citation

Du, J, et al. "Kainate-induced Excitation and Sensitization of Nociceptors in Normal and Inflamed Rat Glabrous Skin." Neuroscience, vol. 137, no. 3, 2006, pp. 999-1013.
Du J, Zhou S, Carlton SM. Kainate-induced excitation and sensitization of nociceptors in normal and inflamed rat glabrous skin. Neuroscience. 2006;137(3):999-1013.
Du, J., Zhou, S., & Carlton, S. M. (2006). Kainate-induced excitation and sensitization of nociceptors in normal and inflamed rat glabrous skin. Neuroscience, 137(3), 999-1013.
Du J, Zhou S, Carlton SM. Kainate-induced Excitation and Sensitization of Nociceptors in Normal and Inflamed Rat Glabrous Skin. Neuroscience. 2006;137(3):999-1013. PubMed PMID: 16330152.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Kainate-induced excitation and sensitization of nociceptors in normal and inflamed rat glabrous skin. AU - Du,J, AU - Zhou,S, AU - Carlton,S M, Y1 - 2005/12/05/ PY - 2005/08/18/received PY - 2005/10/06/revised PY - 2005/10/12/accepted PY - 2005/12/7/pubmed PY - 2006/4/13/medline PY - 2005/12/7/entrez SP - 999 EP - 1013 JF - Neuroscience JO - Neuroscience VL - 137 IS - 3 N2 - This study investigates contributions of peripheral kainate receptors to acute nociception and persistent inflammatory pain in rat. Immunohistochemical analysis of kainate receptor expression using antibodies recognizing glutamate receptor subunits 5, 6, and 7 demonstrates that 28% of unmyelinated axons in normal digital nerve are positively labeled. Following intraplantar injection of complete Freund's adjuvant, a significant increase in glutamate receptor subunits 5, 6, and 7-labeled axons occurs at 2 days (40%), but not 7 (31%) or 14 days (28%) post-complete Freund's adjuvant. In behavioral studies, we confirm an increased mechanical sensitivity in complete Freund's adjuvant-injected hind paws. Furthermore, activation of kainate receptors following intraplantar injection of 1.0 mM kainate in normal animals results in a mechanical sensitivity similar to that observed in inflamed animals. A 1.0 mM kainate injection into inflamed hind paws further enhances the mechanical sensitivity. Injection of the non-N-methyl-D-aspartate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (0.1 mM) reverses complete Freund's adjuvant-induced mechanical sensitivity through a local effect. In single unit recordings from nociceptors in a glabrous skin-nerve preparation, mechanical sensitization is present in inflamed skin evidenced by a decrease in mechanical threshold and an increase in discharge rate during a suprathreshold, constant force stimulus. Thermal sensitization is also present evidenced by a decrease in heat threshold. There is a dose-dependent increase in kainate-induced nociceptor activity in both normal and inflamed skin but the kainate required to induce activation is reduced in inflamed skin. Although proportions of kainate-activated nociceptors are the same in normal and inflamed skin, the kainate-induced mean discharge rate is significantly enhanced in inflamed skin. Exposure of normal and inflamed nociceptors to 0.3 mM kainate sensitizes fibers to re-application of kainate and heat. This sensitization is blocked in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione or the glutamate receptor subunit 5 selective antagonist 3S,4aR,6S,8aR-6-[4-carboxy-phenyl] methyl-1,2,3,4,4a,5,6,7,8,8a-deca-hydroisoquinoline-3-carboxylic acid. The data indicate that peripheral kainate receptors not only play an important role in normal nociception but also contribute to mechanical sensitivity and heat sensitization accompanying inflammatory pain. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/16330152/Kainate_induced_excitation_and_sensitization_of_nociceptors_in_normal_and_inflamed_rat_glabrous_skin_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(05)01151-6 DB - PRIME DP - Unbound Medicine ER -