title: Contribution of peripheral vanilloid receptor to the nociception induced by injection of spermine in mice.
abstract: Polyamines (putrescine, spermidine and spermine) are important endogenous regulators of ion channels, such as vanilloid (TRPV1), glutamatergic (NMDA or AMPA/kainate) and acid-sensitive (ASIC) receptors. In the present study, we have investigated the possible nociceptive effect induced by polyamines and the mechanisms involved in this nociception in vivo. The subcutaneous (s.c.) injection of capsaicin (as positive control), spermine, spermidine or putrescine produced nociception with ED(50) of 0.16 (0.07-0.39)nmol/paw, 0.4 (0.2-0.7) μmol/paw, 0.3 (0.1-0.9) μmol/paw and 3.2 (0.9-11.5) μmol/paw, respectively. The antagonists of NMDA (MK801, 1 nmol/paw), AMPA/kainate (DNQX, 1 nmol/paw) or ASIC receptors (amiloride, 100 nmol/paw) failed to reduce the spermine-trigged nociception. However, the TRPV1 antagonists capsazepine or SB366791 (1 nmol/paw) reduced spermine-induced nociception, with inhibition of 81 ± 10 and 68 ± 9%, respectively. The previous desensitization with resiniferatoxin (RTX) largely reduced the spermine-induced nociception and TRPV1 expression in the sciatic nerve, with reductions of 82 ± 9% and 67 ± 11%, respectively. Furthermore, the combination of spermine (100 nmol/paw) and RTX (0.005 fmol/paw), in doses which alone were not capable of inducing nociception, produced nociceptive behaviors. Moreover, different concentrations of spermine (3-300 μM) enhanced the specific binding of [(3)H]-RTX to TRPV1 receptor. Altogether, polyamines produce spontaneous nociceptive effect through the stimulation of TRPV1, but not of ionotropic glutamate or ASIC receptors.
authors.affiliation: Programa de Pós-Graduação em Farmacologia, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Gewehr
authors.forename: Mariane Arnoldi
authors.initials: MA
authors.lastname: da Silva
authors.forename: Gabriela Trevisan
authors.initials: GT
authors.lastname: dos Santos
authors.forename: Mateus Fortes
authors.initials: MF
authors.lastname: Rossato
authors.forename: Sara Marchesan
authors.initials: SM
authors.lastname: de Oliveira
authors.forename: Carine Cristiane
authors.initials: CC
authors.lastname: Drewes
authors.forename: Andréia Martini
authors.initials: AM
authors.lastname: Pazini
authors.forename: Gustavo Petri
authors.initials: GP
authors.lastname: Guerra
authors.forename: Maribel A
authors.initials: MA
authors.lastname: Rubin
authors.forename: Juliano
authors.initials: J
authors.lastname: Ferreira
mesh_terms: D062565:Acid Sensing Ion Channels; D000818:Animals; D015317:Biogenic Polyamines / Q000494:pharmacology; D015153:Blotting, Western; D004224:Diterpenes / Q000378:metabolism / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D008297:Male; D051379:Mice; D009412:Nerve Fibers / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000187:drug effects; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D010147:Pain Measurement / Q000187:drug effects; D018091:Receptors, AMPA / Q000187:drug effects; D018092:Kainic Acid Receptors / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects; D013096:Spermine / Q000008:administration & dosage / Q000494:pharmacology*; D050916:TRPV Cation Channels / Q000187:drug effects*
chemical_list: D062565:Acid Sensing Ion Channels; D015317:Biogenic Polyamines; D004224:Diterpenes; D018698:Glutamic Acid; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D015222:Sodium Channels; D013096:Spermine; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C024353:resiniferatoxin