Orofacial cold hyperalgesia due to infraorbital nerve constriction injury in rats: reversal by endothelin receptor antagonists but not non-steroidal anti-inflammatory drugs.
The susceptibility of changes in responsiveness to noxious cold stimulation of rats submitted to chronic constriction of the infraorbital nerve (CION) or carrageenan to drug inhibition was compared. Nocifensive responses were measured as total time rats engaged in bilateral facial grooming with both forepaws over the first 2 min following tetrafluoroethane spray application to the snout. Carrageenan (50 microg, s.c. into upper lip) caused short-lived ipsilateral cold hyperalgesia (peak at 3 h: vehicle 8.4+/-1.3, carrageenan 21.2+/-3.0 s) which was markedly suppressed by i.p. indomethacin (4 mg/kg), celecoxib (10mg/kg) or s.c. dexamethasone (0.5 mg/kg), endothelin ET(A) or ET(B) receptor antagonists (BQ-123 and BQ-788, respectively; 10 nmol/lip). CION caused ipsilateral cold hyperalgesia between Days 2 and 12, which peaked on Days 4 (sham 15.3+/-1.8, CION 32.4+/-5.3s) to 6. Established peak CION-induced cold hyperalgesia was unaffected by indomethacin and celecoxib, whereas dexamethasone, BQ-123, BQ-788, and i.v. injections of selective antagonists of ET(A) (atrasentan, 3-10 mg/kg) or ET(B) (A-192621, 5-20 mg/kg) receptors caused significant inhibitions lasting 1-2.5h (peaks approximately 65-90%). Bosentan (dual ET(A)/ET(B) receptor antagonist, 10 mg/kg, i.v.) abolished CION-induced cold hyperalgesia for up to 6h. Thus, once established, CION-induced orofacial hyperalgesia to cold stimuli appears to lack an inflammatory component, but is alleviated by endothelin ET(A) and/or ET(B) receptor antagonists. If this CION injury model bears predictive value to trigeminal neuralgia (i.e., paroxysmal orofacial pain triggered by various stimuli), endothelin receptors might constitute new targets for treatment of this disorder.
Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Juliana Geremias
JG
Chichorro
Aleksander Roberto
AR
Zampronio
Gloria Emilia Petto
GE
Souza
Giles Alexander
GA
Rae
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000077868:Atrasentan; D000077300:Bosentan; D002351:Carrageenan / Q000633:toxicity*; D000068579:Celecoxib; D003080:Cold Temperature / Q000009:adverse effects*; D003907:Dexamethasone / Q000627:therapeutic use; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D019332:Endothelin-1 / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology; D006120:Grooming / Q000187:drug effects*; D006930:Hyperalgesia / Q000188:drug therapy* / Q000503:physiopathology; D007213:Indomethacin / Q000627:therapeutic use; D008297:Male; D008442:Maxillary Nerve / Q000503:physiopathology*; D009408:Nerve Compression Syndromes / Q000188:drug therapy* / Q000503:physiopathology; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology / Q000627:therapeutic use; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D011759:Pyrrolidines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A / Q000187:drug effects* / Q000502:physiology; D044023:Receptor, Endothelin B / Q000187:drug effects* / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D014277:Trigeminal Neuralgia / Q000188:drug therapy* / Q000503:physiopathology
C120508:A 192621; D000894:Anti-Inflammatory Agents, Non-Steroidal; D019332:Endothelin-1; D016232:Endothelins; D009842:Oligopeptides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D010880:Piperidines; D011720:Pyrazoles; D011759:Pyrrolidines; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013449:Sulfonamides; C074308:sovateltide; C086539:BQ 788; D003907:Dexamethasone; D002351:Carrageenan; D000068579:Celecoxib; D000077300:Bosentan; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D000077868:Atrasentan; D007213:Indomethacin