The role of neuropeptides and capsaicin-sensitive fibres in glutamate-induced nociception and paw oedema in mice.
This study sought to establish whether sensory neuropeptides and the capsaicin-sensitive fibres are involved in the nociception and oedema formation caused by intraplantar (i.pl.) injection of glutamate into the mouse paw. The i.pl. co-injection of the selective neurokinin (NK) NK(2) (SR 48968, 0.05-0.5 nmol/paw), and to a lesser extent the selective NK(1) (FK 888, 0.25-1.0 nmol/paw) receptor antagonists, resulted in a significant inhibition of glutamate-induced nociception. The percentages of inhibition were 82 and 37%, respectively. In contrast, the selective NK(3) receptor antagonist (SR 142801, 0.25-1.0 nmol/paw) failed to significantly affect glutamate-induced nociception. SR 48968, but not FK 888 or SR 142801, significantly inhibited (36%) glutamate-induced paw oedema formation. The i.pl. injection of kinin B(1) receptor antagonist des-Arg(9)-[Leu(8)]-BK (0.2-0.8 nmol/paw), but not the B(2) receptor antagonist HOE 140 (1.0-4.0 nmol/paw), together with glutamate, also inhibited glutamate-induced nociception (53%) in a graded manner, without affecting glutamate-induced paw oedema. The i.pl. co-injection of the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP(8-37) (1 nmol/paw) failed to significantly inhibit glutamate-induced nociception or oedema. Finally, neonatal-capsaicin (50 mg/kg, s.c.) treatment inhibited glutamate-induced nociception by 69% and to a lesser extent glutamate-mediated oedema formation (30%). Collectively, the current results indicate that the nociception caused by i.pl. injection of glutamate in mice is clearly mediated by capsaicin-sensitive fibres and by release of neurokinins from sensory neurones that activate NK(2) receptors and to a lesser extent NK(1) receptors. Furthermore, kinins acting at B(1) (but not at B(2)) receptors also largely account for glutamate-mediated nociceptive behaviour response. In contrast, glutamate-induced paw oedema seems to be primarily mediated via activation of NK(2) receptors and stimulation of capsaicin-sensitive C-fibres. CGRP receptors do not seem to be involved in either of the glutamate responses.
Beirith
Alessandra
A
Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Rua Ferreira Lima 82, 88015-420, Florianópolis, SC, Brazil.
Santos
Adair R S
AR
Calixto
João B
JB
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D065168:Bradykinin Receptor Antagonists; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002211:Capsaicin / Q000378:metabolism / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced / Q000503:physiopathology*; D005528:Foot / Q000503:physiopathology; D018698:Glutamic Acid / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D064729:Neurokinin-1 Receptor Antagonists; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D010880:Piperidines / Q000494:pharmacology; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000378:metabolism; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism
D001549:Benzamides; D065168:Bradykinin Receptor Antagonists; D004151:Dipeptides; D007211:Indoles; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D018015:Receptors, Calcitonin Gene-Related Peptide; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; C078949:FK 888; D018698:Glutamic Acid; C073839:SR 48968; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin