title: Imbalance between the expression of NK1 and GABAB receptors in nociceptive spinal neurons during secondary hyperalgesia: a c-Fos study in the monoarthritic rat.
abstract: The neurochemical changes that operate in nociceptive spinal cord circuits during secondary hyperalgesia are largely unknown, in particular with respect to the balance between excitatory and inhibitory neurotransmission. In this study we evaluated the expression of NK1 and GABA(B) receptors in nociceptive spinal neurons in a model of secondary hyperalgesia consisting of noxious mechanical stimulation of the hindlimb skin close to a joint chronically inflamed by complete Freund's adjuvant. In spinal segments receiving input from that skin area, Fos-immunodetection was combined with immunocytochemistry for NK1 receptors, GABA(B) receptors or both receptors. In control and monoarthritic animals, neurons double-labeled for Fos and each receptor occurred mainly in laminae I and IV-V. In lamina I, the percentage of NK1 neurons expressing Fos was higher in monoarthritics while lower percentages of GABA(B) neurons expressed Fos. The percentage of Fos-positive cells expressing NK1 immunoreaction did not change in monoarthritics but that of Fos cells with GABA(B) immunoreaction was lower in these animals. In laminae IV-V, a large increase in Fos expression was detected in monoarthritic rats but the relative proportions of Fos-positive neurons expressing each receptor were similar in the two groups. Co-localization of NK1 and GABA(B) receptors occurred only in lamina I neurons in both experimental groups with no differences between control and monoarthritic animals in the percentages of Fos-positive neurons that expressed the receptors. Considering the participation of lamina I neurons bearing NK1 and GABA(B) receptors in several spinofugal systems, it is possible that the imbalance between excitatory and inhibitory actions exerted, respectively, by substance P and GABA may subserve secondary hyperalgesia by increasing ascending transmission of nociceptive input.
authors.affiliation: Institute of Histology and Embryology, Faculdade de Medicina and IBMC, University of Porto, Portugal.
authors.forename: A R
authors.initials: AR
authors.lastname: Castro
authors.forename: M
authors.initials: M
authors.lastname: Pinto
authors.forename: D
authors.initials: D
authors.lastname: Lima
authors.forename: I
authors.initials: I
authors.lastname: Tavares
mesh_terms: D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000150:complications; D004195:Disease Models, Animal; D005620:Freund's Adjuvant / Q000633:toxicity; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D009475:Neurons, Afferent / Q000378:metabolism*; D009619:Nociceptors / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000096:biosynthesis*; D018040:Receptors, Neurokinin-1 / Q000096:biosynthesis*; D013116:Spinal Cord / Q000378:metabolism*
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D018080:Receptors, GABA-B; D018040:Receptors, Neurokinin-1; D005620:Freund's Adjuvant