Effects of Intracerebroventricular and Intra-Arcuate Nucleus Injection of Ghrelin on Pain Behavioral Responses and Met-Enkephalin and β-Endorphin Concentrations in the Periaqueductal Gray Area in Rats.

Samaneh Pirzadeh,Javad Sajedianfard,Anna Maria Aloisi,Mahboobeh Ashrafi

doi:10.3390/ijms20102475

Samaneh Pirzadeh, Javad Sajedianfard + Show 2 more

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https://doi.org/10.3390/ijms20102475

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Abstract

Ghrelin is an endogenous ligand for orphan growth hormone secretagogue receptors. Ghrelin receptors have been found in central nervous system (CNS) areas responsible for pain modulation and transmission. This study investigated the effects of intracerebroventricular (ICV) and intra-arcuate nucleus (ARC) injection of ghrelin on pain behavioral responses and levels of β-endorphin (β-EP) and met-enkephalin (MENK) in the periaqueductal gray area (PAG) during the formalin test in rats. Thirty-five male rats were studied in five groups. Ghrelin was injected into the left lateral ventricle (ICV, 5 µL) or into the ARC (1 µL). After 15 min, formalin (2.5%) was subcutaneously injected into the left hind paw. Behavioral nociceptive scores were recorded for 60 min. MENK and β-EP were collected by microdialysis in the PAG and determined by high-performance liquid chromatography (HPLC). ICV and ARC injection of ghrelin significantly reduced pain in all phases of the formalin test (p < 0.001). Dialysate concentrations of MENK and β-EP in the PAG increased in all the phases (p < 0.01). In conclusion, the present study shows that the ARC nucleus and the endogenous opioid system are involved in ghrelin-induced pain modulation.

Highlights

Pain is an unpleasant sensory experience caused by intense or damaging stimuli and regulated by the consolidation of complex actions modulated by central factors [1]
Ghrelin is originally secreted by the stomach, but it is found in several regions of the nervous system [3,5,6]; its receptors have been found in different areas of the central nervous system (CNS), including various hypothalamic nuclei such as the arcuate nucleus, other areas of the rat brain such as the hippocampal formation and thalamic regions, and in the spinal cord
ICV and arcuate nucleus (ARC) injection of ghrelin significantly decreased the nociceptive scores in the concentrations of MENK and β-EP in the periaqueductal grey area (PAG), an effect that lasted throughout the formalin test

Summary

Introduction

Pain is an unpleasant sensory experience caused by intense or damaging stimuli and regulated by the consolidation of complex actions modulated by central factors [1]. Ghrelin is originally secreted by the stomach, but it is found in several regions of the nervous system [3,5,6]; its receptors have been found in different areas of the CNS, including various hypothalamic nuclei such as the arcuate nucleus, other areas of the rat brain such as the hippocampal formation and thalamic regions, and in the spinal cord Since many of these structures are responsible for controlling pain transmission [6,7,8,9], ghrelin and its receptors have been suggested to play a key role in the antinociceptive system [10]. Ghrelin has been shown to have an inhibitory effect on inflammatory pain through interference with the central opioid

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