Acute stress-induced antinociception is cGMP-dependent but heme oxygenase-independent

Abstract

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 39,59-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.

Role of TRPV1 channels of the dorsal periaqueductal gray in the modulation of nociception and open elevated plus maze-induced antinociception in mice

“…Besides their role in pain modulation on peripheral primary afferents [13,14], TRPV1 channels have also been involved in the control of pain transmission in the central nervous system [1,2,7,15]. There is also evidence suggesting the participation of vanilloid receptors in brainstem areas involved in the modulation of defensive reactions [3,6] and on the descending pain inhibitory system [2,16,17] in which the midbrain periaqueductal gray matter (PAG) plays a crucial role (e.g.…”