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

P.G Carvalho-Costa,C.R.A Leite-Panissi,L.G.S Branco

doi:10.1590/1414-431x20143926

P.G Carvalho-Costa, C.R.A Leite-Panissi + Show 1 more

Open Access

https://doi.org/10.1590/1414-431x20143926

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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 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.

Highlights

The exposure of animals to threatening situations of either an innate or learned nature results in species-specific defensive behaviors, autonomic alterations and pain inhibition
The results of the present study confirmed that acute stress induced antinociception (Figure 1), but neither heme-lysinate nor ZnDPBG altered the analgesia index (AI) in rats that were evaluated using the tail flick test
The post-hoc Newman-Keuls test showed that the AIs in the ZnDPBG and Na2CO3 groups were different (P,0.05) at all experimental times when compared with the respective baseline values (P,0.05, Newman-Keuls test, Figure 1A)

Summary

Introduction

The exposure of animals to threatening situations of either an innate or learned nature results in species-specific defensive behaviors, autonomic alterations and pain inhibition These reactions are crucial for the survival of the species [1]. A number of studies have shown that the antinociceptive system can be activated by a variety of external or environmental noxious stimuli and plays an important role in control of defensive affective behaviors [2]. In this context, fear induced by conditioned or unconditioned aversive stimuli is known to inhibit behavioral responses to pain [3]. Chronic stress may not interfere with nociception because an adaptation to stressful stimuli may take place or may even promote hypernociception [5]

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