Galanin Receptor 1 Plays an Antinociceptive Effect via Inhibiting PKA Activation in the Nucleus Accumbens of Rats With Neuropathic Pain

Galanin and galanin receptors (GalRs) have been reported to be involved in the transmission and modulation of nociceptive information in the central nervous system (CNS). However, the underlying mechanism of the antinociception of GalRs in neuropathic pain remains unclear. This study investigated the antinociception induced by galanin receptor 1 (GalR1) via protein kinase A (PKA) signaling pathway in the nucleus accumbens (NAc) of rats with neuropathic pain. A mononeuropathy model was replicated by ligation of the left sciatic nerve, following which the expression of phospho-PKA (p-PKA) in the NAc were markedly up-regulated at 14th and 28th day after ligation of sciatic nerve, and p-PKA expression was down-regulated by intra-NAc injection of GalR1 agonist M617, but the GalR1 antagonist M35 did not have an effect. We also found that M35 in the NAc blocked the M617-induced increase in the hind paw withdrawal latencies (HWLs) of rats with mononeuropathy, but M35 alone had no effect on HWLs, and PKA inhibitor H-89 attenuated the M617-induced an increase in the HWLs. These results suggested that GalR1 induced an antinociception via inhibiting PKA activation, implying that GalR agonists may be potential and potent therapeutic options to treat chronic neuropathic pain.

Central Administration of Galanin Receptor 1 Agonist Boosted Insulin Sensitivity in Adipose Cells of Diabetic Rats

Our previous studies testified the beneficial effect of central galanin on insulin sensitivity of type 2 diabetic rats. The aim of the study was further to investigate whether central M617, a galanin receptor 1 agonist, can benefit insulin sensitivity. The effects of intracerebroventricular administration of M617 on insulin sensitivity and insulin signaling were evaluated in adipose tissues of type 2 diabetic rats. The results showed that central injection of M617 significantly increased plasma adiponectin contents, glucose infusion rates in hyperinsulinemic-euglycemic clamp tests, GLUT4 mRNA expression levels, GLUT4 contents in plasma membranes, and total cell membranes of the adipose cells but reduced the plasma C-reactive protein concentration in nondiabetic and diabetic rats. The ratios of GLUT4 contents were higher in plasma membranes to total cell membranes in both nondiabetic and diabetic M617 groups than each control. In addition, the central administration of M617 enhanced the ratios of pAkt/Akt and pAS160/AS160, but not phosphorylative cAMP response element-binding protein (pCREB)/CREB in the adipose cells of nondiabetic and diabetic rats. These results suggest that excitation of central galanin receptor 1 facilitates insulin sensitivity via activation of the Akt/AS160 signaling pathway in the fat cells of type 2 diabetic rats.