Role of the spinal cord heme oxygenase-carbon monoxide-cGMP pathway in the nociceptive response of rats.
The aim of the present study was to investigate the role of the spinal cord heme oxygenase (HO)-carbon monoxide (CO)-soluble guanylate cyclase (sGC)-cGMP pathway in nociceptive response of rats to the formalin experimental nociceptive model. Animals were handled and adapted to the experimental environment for a few days before the formalin test was applied. For the formalin test 50 microl of a 1% formalin solution was injected subcutaneously in the dorsal surface of the right hind paw. Following injections, animals were observed for 1 h and flinching behavior was measured as the nociceptive response. Thirty min before the test, rats were pretreated with intrathecal injections with the HO inhibitor, zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG) or heme-lysinate, which is known to induce the HO pathway. Control animals were treated with vehicles. We observed a significant increase in nociceptive response of rats treated with ZnDPBG, and a drastic reduction of flinching nociceptive behavioral response in the heme-lysinate treated animals. Furthermore, the HO pathway seems to act via cGMP, since methylene blue (a sGC inhibitor) prevented the reduction of flinching nociceptive behavioral response caused by heme-lysinate. These findings strongly indicate that the HO pathway plays a spinal antinociceptive role during the formalin test, acting via cGMP.
Nascimento
Carlos G O
CG
Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, São Paulo, Brazil.
Branco
Luiz G S
LG
D000818:Animals; D002248:Carbon Monoxide / Q000502:physiology*; D006152:Cyclic GMP / Q000502:physiology*; D003905:Deuteroporphyrins / Q000494:pharmacology; D006418:Heme / Q000031:analogs & derivatives / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000502:physiology*; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000502:physiology*
D003905:Deuteroporphyrins; 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; D008751:Methylene Blue