Nociceptive transmitter release in the dorsal spinal cord by capsaicin-sensitive fibers after noxious gastric stimulation.
Little is known about transmitters that encode noxious gastric stimuli in the spinal cord. The release of glutamate, substance P, and CGRP from the spinal cord was therefore investigated in response to acid injury of the gastric mucosa. Dorsal halves of the caudal thoracic spinal cord (T7-T13) were removed 6 h after oral application of 0.5 M HCl or saline, transferred to a superfusion chamber, and the basal and capsaicin-stimulated (3.3 microM) transmitter release was determined. After acid injury, basal glutamate release increased 134% as compared to saline-treated animals. Capsaicin-stimulated release of CGRP and SP was 48% and 58% lower in acid- than in saline-treated animals, indicating that capsaicin-sensitive fibers in the dorsal spinal cord were already partially depleted by acid treatment. Capsaicin denervation reduced basal glutamate release by 33% after acid injury as compared to non-denervated acid-treated animals. Gastric origin and capsaicin sensitivity of glutamatergic, CGRP- and SP-containing primary afferents in thoracic dorsal root ganglia were then determined by retrograde tracing with True Blue and immunohistochemical labeling with the vanilloid receptor TRPV1. About 65% of True Blue-labeled cells were glutamatergic and more than 73% of this population expressed the TRPV1 receptor. Nearly all True Blue/CGRP (85%)- and True Blue/SP-positive cells (97%) coexpressed TRPV1. We conclude that noxious gastric stimulation with acid induces release of glutamate, SP, and CGRP from capsaicin-sensitive sensory afferents in the dorsal horn of the spinal cord where they may play an important role in gastric nociception and hyperalgesia.
Schicho
Rudolf
R
Department of Experimental and Clinical Pharmacology, Medical University of Graz, Universitätsplatz 4, A-8010 Graz, Austria. rudolf.schicho@meduni-graz.at
Donnerer
Josef
J
Liebmann
Ingrid
I
Lippe
Irmgard Th
IT
D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D000818:Animals; D017763:Autonomic Denervation; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000293:injuries / Q000294:innervation; D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000378:metabolism*; D007150:Immunohistochemistry; D007473:Ion Channels / Q000378:metabolism; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000378:metabolism*; D027981:Symporters / Q000378:metabolism; D050916:TRPV Cation Channels; D013904:Thoracic Vertebrae; D017833:Visceral Afferents / Q000187:drug effects / Q000378:metabolism*
D027322:Amino Acid Transport System X-AG; D050491:Glutamate Plasma Membrane Transport Proteins; D007473:Ion Channels; D027981:Symporters; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D013373:Substance P; D018698:Glutamic Acid; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin