Acute stress-induced antinociception is cGMP-dependent but heme oxygenase-independent.
Endogenous carbon monoxide (CO), which is produced by the enzyme heme oxygenase (HO), participates as a neuromodulator in physiological processes such as thermoregulation and nociception by stimulating the formation of 3',5'-cyclic guanosine monophosphate (cGMP). In particular, the acute physical restraint-induced fever of rats can be blocked by inhibiting the enzyme HO. A previous study reported that the HO-CO-cGMP pathway plays a key phasic antinociceptive role in modulating noninflammatory acute pain. Thus, this study evaluated the involvement of the HO-CO-cGMP pathway in antinociception induced by acute stress in male Wistar rats (250-300 g; n=8/group) using the analgesia index (AI) in the tail flick test. The results showed that antinociception induced by acute stress was not dependent on the HO-CO-cGMP pathway, as neither treatment with the HO inhibitor ZnDBPG nor heme-lysinate altered the AI. However, antinociception was dependent on cGMP activity because pretreatment with the guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) blocked the increase in the AI induced by acute stress.
Programa de Graduação em Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
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Carvalho-Costa
Departamento de Morfologia, Fisiologia e Patologia Básica, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
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Branco
Programa de Graduação em Psicobiologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil.
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Leite-Panissi
D059787:Acute Pain / Q000517:prevention & control*; D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism*; D006152:Cyclic GMP / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003905:Deuteroporphyrins / Q000378:metabolism; D006418:Heme / Q000031:analogs & derivatives / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D059226:Nociceptive Pain / Q000378:metabolism / Q000517:prevention & control*; D010069:Oxadiazoles / Q000494:pharmacology; D010147:Pain Measurement / Q000379:methods; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D040701:Stress Disorders, Traumatic, Acute / Q000378:metabolism*
D003905:Deuteroporphyrins; D010069:Oxadiazoles; C106087:heme lysinate; C060750:zinc deuteroporphyrin IX 2,4-bis(glycol); D006418:Heme; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); D006152:Cyclic GMP; D008239:Lysine