Antinociception synergy between the peripheral and spinal sites of the heme oxygenase-carbon monoxide pathway
Braz. j. med. biol. res
;
42(1): 141-147, Jan. 2009. graf
Article
Dans Anglais
| LILACS
| ID: lil-505420
ABSTRACT
We have shown that the peripheral and spinal cord heme oxygenase (HO)-carbon monoxide (CO)-soluble guanylate cyclase-cGMP pathways play an important role in antinociception in the rat experimental formalin model. Our objective was to determine if there is synergism between peripheral (paw) and spinal HO-CO pathways in nociception. Rats were handled and adapted to the experimental environment for a few days before the formalin test, in which 50 µL of a 1 percent formalin was injected subcutaneously into the dorsal surface of the right hind paw. The animals were then observed for 1 h and the frequency of flinching behavior was taken to represent the nociceptive response. Thirty minutes before the test, rats were pretreated with intrathecal injections of the HO inhibitor, zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG) or heme-lysinate, which is a substrate of the HO pathway. The paw treatments took place 20 min before the test. Low doses of ZnDPBG did not increase nociception, while a low heme-lysinate dose did not change flinching behavior after paw or spinal injections. Combined subactive spinal (50 nmol) and peripheral (40 nmol) low doses of ZnDPBG induced hypernociception (increase of 80 percent in the first and 25 percent in the second phase flinching), whereas combined spinal-peripheral heme-lysinate (50 and 30 nmol) led to second phase antinociception (40 percent reduction in flinching). These findings suggest a synergy between the peripheral and spinal HO-CO pathways. Local activation of the HO system probably regulates the nociception initiation in peripheral tissue and participates in buffering the emerging nociceptive signals at the peripheral and spinal sites of action. In short, an antinociceptive synergy exists between peripheral and spinal HO pathways, which may reduce the doses required and side effects.
Texte intégral:
Disponible
Indice:
LILAS (Amériques)
Sujet Principal:
Moelle spinale
/
Mesure de la douleur
/
Nocicepteurs
/
Monoxyde de carbone
/
Récepteurs cytoplasmiques et nucléaires
/
Guanylate cyclase
/
Heme oxygenase (decyclizing)
Type d'étude:
Étude pronostique
Limites du sujet:
Animaux
langue:
Anglais
Texte intégral:
Braz. j. med. biol. res
Thème du journal:
Biologie
/
Médicament
Année:
2009
Type:
Article
/
Congrès et conférence
Pays d'affiliation:
Brésil
Institution/Pays d'affiliation:
Universidade de São Paulo/BR
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