A role of supraspinal galanin in behavioural hyperalgesia in the rat.

Diana Amorim,Antti Pertovaara,Ana David-Pereira,Patrícia Rebelo,Patrícia Marques,Filipa Pinto-Ribeiro,Sónia Puga,Patrício Costa,Armando Almeida

doi:10.1371/journal.pone.0113077

Diana Amorim, Antti Pertovaara + Show 7 more

Open Access

https://doi.org/10.1371/journal.pone.0113077

Copy DOI

Journal: PloS one	Publication Date: Nov 18, 2014
Citations: 80	License type: CC BY 4.0

Affiliation: University of Minho, University of Helsinki

Abstract

IntroductionIn chronic pain disorders, galanin (GAL) is able to either facilitate or inhibit nociception in the spinal cord but the contribution of supraspinal galanin to pain signalling is mostly unknown. The dorsomedial nucleus of the hypothalamus (DMH) is rich in galanin receptors (GALR) and is involved in behavioural hyperalgesia. In this study, we evaluated the contribution of supraspinal GAL to behavioural hyperalgesia in experimental monoarthritis.MethodsIn Wistar-Han males with a four week kaolin/carrageenan-induced monoarthritis (ARTH), paw-withdrawal latency (PWL) was assessed before and after DMH administration of exogenous GAL, a non-specific GALR antagonist (M40), a specific GALR1 agonist (M617) and a specific GALR2 antagonist (M871). Additionally, the analysis of c-Fos expression after GAL injection in the DMH was used to investigate the potential involvement of brainstem pain control centres. Finally, electrophysiological recordings were performed to evaluate whether pronociceptive On- or antinociceptive Off-like cells in the rostral ventromedial medulla (RVM) relay the effect of GAL.ResultsExogenous GAL in the DMH decreased PWL in ARTH and SHAM animals, an effect that was mimicked by a GALR1 agonist (M617). In SHAM animals, an unselective GALR antagonist (M40) increased PWL, while a GALR2 antagonist (M871) decreased PWL. M40 or M871 failed to influence PWL in ARTH animals. Exogenous GAL increased c-Fos expression in the RVM and dorsal raphe nucleus (DRN), with effects being more prominent in SHAM than ARTH animals. Exogenous GAL failed to influence activity of RVM On- or Off-like cells of SHAM and ARTH animals.ConclusionsOverall, exogenous GAL in the DMH had a pronociceptive effect that is mediated by GALR1 in healthy and arthritic animals and is associated with alterations of c-Fos expression in RVM and DRN that are serotonergic brainstem nuclei known to be involved in the regulation of pain.

Highlights

In chronic pain disorders, galanin (GAL) is able to either facilitate or inhibit nociception in the spinal cord but the contribution of supraspinal galanin to pain signalling is mostly unknown
In basal conditions several studies showed that, both in humans and rodents, GAL is expressed in the supraoptic nucleus, the paraventricular nucleus of the hypothalamus, the dorsomedial hypothalamic nucleus (DMH), the arcuate nuclei, the lateral hypothalamic area, the locus coeruleus (LC), the amygdala (AMY) and the median raphe nucleus [6], all areas involved in supraspinal pain modulation [7,8,9,10,11]
As hyperalgesia is one of the hallmarks of chronic pain, activation of the dorsomedial nucleus of the hypothalamus (DMH) promotes behavioural hyperalgesia and GAL receptors are strongly expressed in the DMH, here we evaluated the contribution of GAL receptors in the DMH to the descending control of inflammatory hyperalgesia in monoarthritis as well as nociception in healthy controls

Summary

Introduction

Galanin (GAL) is able to either facilitate or inhibit nociception in the spinal cord but the contribution of supraspinal galanin to pain signalling is mostly unknown. The dorsomedial nucleus of the hypothalamus (DMH) is rich in galanin receptors (GALR) and is involved in behavioural hyperalgesia. In basal conditions several studies showed that, both in humans and rodents, GAL is expressed in the supraoptic nucleus, the paraventricular nucleus of the hypothalamus, the dorsomedial hypothalamic nucleus (DMH), the arcuate nuclei, the lateral hypothalamic area, the locus coeruleus (LC), the amygdala (AMY) and the median raphe nucleus [6], all areas involved in supraspinal pain modulation [7,8,9,10,11]. In relation to receptor expression, GALR1 is greatly expressed in the LC, dorsal raphe nucleus (DRN), the paraventricular nucleus of the hypothalamus, DMH, AMY, thalamus and medulla oblongata [12,13,14,15]. Most brain areas mentioned above are involved in the codification and modulation of nociceptive inputs [7,10]

Methods

Results

Discussion

Conclusion