Involvement of the heme oxygenase-carbon monoxide-cGMP pathway in the nociception induced by acute painful stimulus in rats

Author(s)

Carvalho, Priscila G. ^[1] ; Branco, Luiz G. S. ; Andrade Leite-Panissi, Christie Ramos ^[2]

Affiliation

^[1] Univ Sao Paulo, Sch Philosophy Sci & Literature Ribeirao Preto, Psychobiol Postgrad Program, BR-14040901 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Odontol Ribeirao Preto, Dent Sch Ribeirao Preto, Dept Morphol Stomatol & Physiol, BR-14040904 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: Brain Research; v. 1385, p. 107-113, APR 18 2011.
• Web of Science Citations: 12

Abstract

Heme oxygenase-carbon monoxide-cGMP (HO-CO-cGMP) pathway has been reported to be involved in peripheral and spinal modulation of inflammatory pain. However, the involvement of this pathway in the modulation of acute painful stimulus in the absence of inflammation remains unknown. Thus, we evaluated the involvement of the HO-CO-cGMP pathway in nociception by means the of analgesia index (AI) in the tail flick test. Rats underwent surgery for implantation of unilateral guide cannula directed toward the lateral ventricle and after the recovery period (5-7 days) were subjected to the measures of baseline tail flick test Animals were divided into groups to assess the effect of intracerebroventricular administration (i.c.v.) of the following compounds: ZnDPBG (HO inhibitor) or vehicle (Na(2)CO(3)), heme-lysinate (substrate overload) or vehicle (L-lysine), or the selective inhibitor of soluble guanilate cyclase ODQ or vehicle (DMSO 1%) following the administration of heme-lysinate or vehicle. Heme overload increased AI, indicating an antinociceptive role of the pathway. This response was attenuated by i.c.v. pretreatment with the HO inhibitor ZnDPBG. In addition, this effect was dependent on cGMP activity, since the pretreatment with ODQ blocked the increase in the AI. Because CO produces most of its actions via cGMP, these data strongly imply that CO is the HO product involved in the antinociceptive response. This modulation seems to be phasic rather than tonic, since i.c.v. treatment with ZnDPBG or ODQ did not alter the AI. Therefore, we provide evidence consistent with the notion that HO-CO-cGMP pathway plays a key phasic antinociceptive role modulating noninflammatory acute pain. (C) 2011 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 05/00096-1 - Functional anatomy evaluation of the defensive behavior of tonic immobility in guinea pigs
• Grantee: Christie Ramos Andrade Leite Panissi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 07/08122-7 - HO-CO-cGMP pathway in the antinociception induced by stress in rats.
• Grantee: Christie Ramos Andrade Leite Panissi
• Support Opportunities: Regular Research Grants