| Objective:It has been reported that galanin and its receptors might be involved in the modulation and transmission of nociception in the central nervous system. Our previous research has also demonstrated that galanin induces antinociception in the nucleus accumbens (NAc) of intact rats. However, the interaction between galanin and its receptors in the NAc and the underlying mechanism of suppressing pain transmission remain unclear. The present study seeks to determine the antinociception induced by galanin receptor1 (GalRl) stimulation in the NAc of rats with neuropathic pain.Methods:1. The left sciatic nerve of rats was ligated to mimic a Sciatica model. The experimental protocol for duplicating mononeuropathic pain in rats was similar to that described by Bennett and Xie (1988), which was characterized by spontaneous burning pain combined with hyperalgesia and allodynia to mechanical and/or thermal stimulation.2. Western blots used to determine the expression of GalR1 in the NAc of rats with neuropathic pain and rats with sham operation.3. Four groups of rats received different intra-NAc injections,1) 1μl of 0.9% saline as control group (n=6);2) 1μ of 0.9% saline with 0.05nmol M617 (n= 7); 3) 1μl of 0.9%s aline with 0.5nmol M617 (n=7); 4) 1μl of 0.9% saline with 1nmol M617 (n=7).4. Rats with left sciatic nerve ligation received intra-NAc injection of lnmol M617(n=7), and the intact rats received the same dose of M617 as a control group (n=6).5. Two groups of rats received intra-NAc injection of lnmol M617. followed 5 min later by intra-NAc injection of 1μl of 0.9% saline with lnmol M35 (n=7) or 1μl of 0.9% saline as control (n=6).6. Two groups of rats received intra-NAc injection of 0.5nmol galanin, followed 5 min later by intra-NAc injection of lnmol of M35 (n=7) or 1μl of 0.9% saline as a control (n=7).7. To compare the antinociception induced by M617 and galanin, three groups received intra-NAc injection of lμl of 0.9% saline with 0.5nmol M617 (n=7),1μl of 0.9% saline with 0.5nmol galanin (n=7), and 1μl of 0.9% saline as control (n=7).Results:The left sciatic nerve of rats was ligated to mimic a sciatica model. Western blots showed that the expression of GalR1 was significantly upregulated in the NAc of rats with neuropathic pain. Intra-NAc injection of GalRl agonist M617 induced a dose-dependent increase in hindpaw withdrawal latency (HWL) to noxious thermal and mechanical stimulations in rats with neuropathic pain. Also, the effect of M617 was attenuated by M35, a GalR1/2 antagonist; at the same time, M35 reduced the galanin-induced antinociception, suggesting that GalR1 mediates antinociception induced by galanin in the NAc of rats with neuropathic pain. Furthermore, we found that M617-induced antinociception in rats with neuropathic pain was stronger than the antinociception in intact rats. We also found that injections of M617 and galanin each induced significant increases in HWL, but the galanin-induced anti-nociception was stronger than that of M617.Conclusion:All these results suggest that GalR1 plays an important role in anti-nociception and that other GalRs also are involved in pain modulation induced by galanin in the NAc of rats with neuropathic pain. |
