Elsevier

Brain Research

Volume 1320, 12 March 2010, Pages 16-21
Brain Research

Research Report
Antinociceptive effects of galanin in the central nucleus of amygdala of rats, an involvement of opioid receptors

https://doi.org/10.1016/j.brainres.2009.12.060Get rights and content

Abstract

The central nucleus of amygdala (CeA) is a very important brain structure involved in multiple physiological functions, especially in pain modulation. There are high densities of galanin and galanin receptors found in the CeA. The present study was performed to explore the antinociceptive effects of galanin in the CeA of rats, and possible involvements of opioid receptors in the galanin-induced antinociception. Intra-CeA injection of galanin induced dose-dependent increases in hindpaw withdrawal latencies (HWLs) to noxious thermal and mechanical stimulations in rats. Interestingly, the amtinociceptive effect induced by intra-CeA injection of galanin was blocked by intra-CeA injection of naloxone, a common opioid receptor antagonist, indicating an involvement of opioid receptors in the galanin-induced antinociception in the CeA of rats. Moreover, intra-CeA injection of either selective mu-opioid receptor antagonist β-funaltrexamine (β-FNA) or delta-opioid receptor antagonist naltrindole, but not kappa-opioid receptor antagonist nor-binaltorphimine (nor-BNI), significantly attenuated the galanin-induced increases in HWLs in the CeA of rats. Taken together, the results demonstrate that galanin induces antinociceptive effects in the CeA of rats, and both mu- and delta-opioid receptors are involved in the galanin-induced antinociception.

Introduction

Galanin, a 29 (30 in human) amino acid residue neuropeptide, is widely distributed in the central nervous system and peripheral tissues (Melander et al., 1986, Merchenthaler et al., 1993, Robinson and Brewer, 2008). Galanin has been shown to participate in a variety of physiological functions, such as reproduction, memory and food intake (Counts et al., 2008, Hobson et al., 2008, Merchenthaler et al., 1993, Rajendren, 2002, Taylor et al., 2009). There are three galanin receptors subtypes, GalR1, GalR2 and GalR3, and all the galanin receptors are G protein coupled receptors (Branchek et al., 2000, Robinson and Brewer, 2008).

Numerous studies have demonstrated that galanin and its receptors are involved in the transmission and modulation of nociceptive information at spinal levels (Hua et al., 2004, Liu and Hokfelt, 2002, Wiesenfeld-Hallin et al., 2005, Xu et al., 2008, Zhang et al., 2000). In the brain, studies have demonstrated that galanin plays an antinociceptive role in the hypothalamic arcuate nucleus in intact rats, in rats with inflammation and in rats with chronic neuropathic pain (Gu et al., 2007, Sun et al., 2003), indicating that galanin and galanin receptors play an important role in the antinociception modulation in the central nervous system. Wang et al. also found that galanin and galanin receptors are involved in pain modulation in periaqueductal grey (PAG) of rats (Sun and Yu, 2005, Wang et al., 1999). Interestingly, previous studies also demonstrated an interaction between galanin and opioids in nociceptive modulation in the spinal cord (Zhang et al., 2000), as well as in the brain (Sun and Yu, 2005, Wang et al., 1999).

The central nucleus of amygdala (CeA) is a very important brain structure involved in multiple physiological functions (Ahn and Phillips, 2002, Beckman et al., 2009, Goncalves et al., 2008, Han and Yu, 2009). Bie et al. investigated the potential adaptive function of delta opioid receptor in neurons of the CeA and found that in rats displaying morphine-induced behavior of conditioned place preference the overall synaptic strength of glutamate synapses in CeA neurons was significantly enhanced, implying an involvement of delta opioid receptor in opioid reward and addiction in the CeA (Bie et al., 2009). Recently, Beckman et al. (2009) reported that opioid activity in the CeA can modulate the feeding inhibition of melanocortin stimulation of the hypothalamic paraventricular nucleus. Studies have demonstrated that the CeA is involved in pain modulation in the central nervous system (Goncalves et al., 2008, Han and Yu, 2009, Neugebauer et al., 2004, Xu et al., 2003). Both high densities of galanin and galanin receptors are found in the CeA (Melander et al., 1986, Merchenthaler et al., 1993, Mennicken et al., 2002). These reports strongly suggest a nociceptive modulation role of galanin in the CeA. Therefore, the present study was performed to explore the antinociceptive effects of galanin in the CeA of rats, and possible involvements of opioid receptors in the galanin-induced antinociception.

Section snippets

Antinociceptive effects of galanin in the CeA of rats

Four groups of rats received intra-CeA injection of 0.1 (n = 8), 0.5 (n = 7) or 1 nmol (n = 8) of galanin, or 1 μl of 0.9% saline as a control (n = 7). As shown in Fig. 1, the HWLs to thermal and mechanical stimulations increased significantly in a dose-dependent manner after intra-CeA injection of 0.1 nmol of galanin (Hot-plate Test: Fleft/left (1,13) = 10.62, P < 0.01; Fright/right (1,13) = 14.30, P < 0.01; Randall Selitto Test: Fleft/left (1,13) = 10.00, P < 0.01; Fright/right (1,13) = 5.05, P < 0.05), 0.5 nmol of

Discussion

Lots of studies have demonstrated that galanin and its receptors play important roles in the transmission and modulation of nociceptive information in the spinal cord (Hua et al., 2004, Liu and Hokfelt, 2002, Wiesenfeld-Hallin et al., 2005, Xu et al., 2008, Zhang et al., 2000). There are very few reports related to the roles of galanin in pain modulation at supraspinal levels. Previous studies in our laboratory demonstrated that galanin and galanin receptors are involved in the pain modulation

Animals

All experiments were carried out on freely moving male Wister rats weighing between 200 and 250 g (Experimental Animal Center, Academy of Military Medical Sciences, Beijing, China). The rats were housed in cages with free access to food and water, and maintained in a room temperature of 24 ± 2 °C with a normal day/night cycle. All experiments were performed according to the guidelines of the International Association for the Study of Pain (Zimmermann, 1983) and every effort was made to minimize

Acknowledgments

The work is supported by funds from the National Natural Science Foundation of China (NSFC 30470542, 30870802), National Ministry of Education grant (20040001057), National Undergraduate Innovative Test Program Research Endowment sponsored by the National Ministry of Education and National Program of Basic Research sponsored by the Ministry of Science andTechnology of China (2006CB500706, 2009CB522002).

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