Inflammatory pain is very common in the clinic A

Inflammatory pain is very common in the clinic. A study demonstrated that galanin was upregulated after nerve injury or inflammation (Ma and Bisby, 1997). It has been reported that galanin plays an important role in the transmission of nociceptive information in the spinal cord of rats with inflammation, and opioid systems are involved in the galanin-induced antinociception (Xiong et al., 2005). Sun et al. reported that galanin had an antinociceptive role in the arcuate nucleus of hypothalamus of intact rats and rats with inflammation (Sun et al., 2003). The results indicated that galanin played a significant role in the transmission of nociceptive information in the spinal cord and glycoprotein iib iiia inhibitors of rats with inflammation. Although a multitude of studies have proved that the NAc is an important limbic structure of the brain with roles in pain modulation (Gu and Yu, 2007, Jin et al., 2010, Li et al., 2010, Xu et al., 2012a), the underlying antinociceptive mechanism of galanin and especially galanin receptors in NAc remain largely unclear. Therefore, the present study investigated whether galanin and its receptors were involved in the modulation of nociceptive information in the NAc of rats with inflammatory pain.
Materials and methods
Results
Discussion Carrageenin-induced inflammation is a commonly used model for the study of edema formation and nociception (Mayer et al., 1988, Satoh et al., 1992). Hargreaves et al. (1988) described that Carrageenan-induced inflammation resulted in significantly shorter paw withdrawal latencies as compared to saline-treated paws (Hargreaves et al., 1988). The present study showed that subcutaneous injection of carrageenin into the left hindpaw induced bilateral decreases in the HWLs, which was more pronounced in the carrageenin injected paw. The results consist with other previous studies (Yu et al., 1996, Yu et al., 1998, Sun et al., 2003, Xiong et al., 2005). These findings indicate that there is a link whereby increased activity in sensory neurons on one side of the body can induce reciprocal changes within the dorsal horn and dorsal root ganglia on the opposite side (Levine et al., 1985, Mapp et al., 1993). In previous studies, it has been reported that galanin plays an important role in the transmission of nociceptive information in the spinal cord (Xiong et al., 2005) and in the arcuate nucleus of hypothalamus (Sun et al., 2003) of rats with inflammation. The NAc is one of the most important sites involved in pain modulation. Gear et al. reported that the NAc plays an important role in mediating the suppression of tonic or persistent pain (Gear et al., 1999). On the afferent side, Burstein et al. used retrograde labeling techniques to show that hundreds of neurons in the spinal cord project directly to the NAc (Burstein and Giesler, 1989). On the efferent side, the NAc projects to the amygdala and ventral pallidum (Heimer et al., 1991). It has been demonstrated that neurotransmitters, including dopamine (Taylor et al., 2003), gamma-amino butyric acid (Saul'skaya and Marsden, 1998), N-methyl-d-aspartate (Zhang et al., 2004), as well as neuropeptides such as opioid peptides (Li et al., 2002), neurokinin (Altier and Stewart, 1997), neuropeptide Y (Li et al., 2002) are involved in nociceptive modulation in the NAc. These studies proposed that NAc may play a critical role in diverse conditions that produce pain and analgesia (Gu and Yu, 2007, Li et al., 2010, Gear and Levine, 2011). Therefore, it is interesting to study whether galanin and its receptors play a role in pain modulation in the NAc of rats with inflammation. Studies identified that the physiological effects of galanin were mediated by the activation of galanin receptors (Hobson et al., 2008). It is known that there are three types of galanin receptors, GalR1, GalR2 and GalR3 (Branchek et al., 2000). In situ hybridization and reverse transcriptase-polymerase chain reaction (PCR) data indicated the distribution of rat GalR1 mRNA in the hypothalamus (supraoptic nucleus), amygdala, ventral hippocampus, thalamus, brainstem (medulla oblongata, locus coeruleus and lateral parabrachial nucleus), spinal dorsal horn and dorsal root ganglion (Parker et al., 1995, Burgevin et al., 1995, Gustafson et al., 1996). GalR2 mRNA has been localized to hypothalamic nuclei, hippocampus, amygdala, several regions of the cortex and the dorsal root ganglion (Depczynski et al., 1998, Kolakowski et al., 1998, O’Donnell et al., 1999). Very low levels or no expression of GalR3 mRNA is found in the dorsal root ganglion (Mennicken et al., 2002). Galanin receptors might be active in hyperalgesic states such as neuropathological pain. Xu et al. demonstrated that GalR1 expression was downregulated in dorsal root ganglion but upregulated in spinal dorsal horn, whereas GalR2 was upregulated in both dorsal root ganglion and spinal dorsal horn after sciatic nerve-pinch injury (Xu et al., 2012b). In this study, we found that both GalR1 and GalR2 expression were upregulated in NAc of rats with inflammation, indicating GalR1 and GalR2 also might be activated during suffering from inflammatory pain.