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  • At the end of experiments

    2021-10-23

    At the end of experiments rats were injected high dose of sodium pentobarbital (90mg/kg) and the rat’s head was cut and frozen in −20°C for 20min with the injecting tube in situ before section. The location of the tip of the injecting tube was verified and all the tips of the injecting tube were in the PAG of rats in the present study, as shown in Fig. 1. Solutions for intra-PAG injection were prepared with sterilized saline (0.9%), each with a volume of 1μl of 2nmol of galanin (Tocris Bioscience company, UK), 0.1, 0.5 or 1nmol of M871 (the selective galanin receptor 2 antagonist, Tocris Bioscience company, UK), or 0.1, 1, 5, or 10μg of MAP (myristoylated autocamtide-2-inhibitory peptide, MAP, a selective CaMKII inhibitor; GL Biochem, Shanghai). One microliter of 0.9% saline was injected as a control. Data from nociceptive tests were expressed as mean±S.E.M. Statistical difference between groups was determined by Student’s t test (two-tailed). *P<0.05, **P<0.01 and ***P<0.001 were considered as significant differences.
    Discussion Wang et al. demonstrated that intra-PAG injection of galanin induced significant antinociceptive effects in rats [16]. In order to determine whether GalR2 is involved in galanin-induced antinociception in PAG, using the GalR2 antagonist M871, the present study demonstrated that intra-PAG injection of M871 attenuated the galanin induced antinociception dose-dependently, indicating an involvement of GalR2 in galanin-induced antinociception in PAG of rats. Furthermore, intra-PAG administration of the CaMKII inhibitor MAP inhibited the galanin induced antinociception, indicating that CaMKII may be involved in the galanin-induced antinociception in PAG of rats. CaMKII is a common molecular involved in the cellular signal pathway of G-protein coupled receptor [10], and it has been demonstrated to be involved in pain modulation, especially in central neuropathic pain and other pathological pain [3], [4], [9]. It is known that activation of GalR2 induces increases in the content of Ca2+ [10], the increased content of Ca2+ may activate CaMKII and then induces nociceptive modulation in the central Boc-D-Asp(OtBu)-OH.DCHA mg [11], [17]. Crown et al. reported that CaMKII contributed to persistent central neuropathic pain following spinal cord injury [3]. Ferhatovic et al. reported the relationship of CaMKII expression and pain-related behavior in rat models of type 1 and type 2 diabetes [4]. Interestingly, Kadic and his collogues demonstrated that the effects of intra-ganglionic injection of CaMKII inhibitors on pain-related behavior in diabetic neuropathy [9]. In the present study, intra-PAG administration of the CaMKII inhibitor MAP inhibited the galanin induced antinociception, indicating that CaMKII may be involved in the cellular signal pathway of GalR2 in galanin-induced antinociception in PAG of rats.
    Acknowledgements The study is supported by grants from XIETONG Foundation of Yantai University, and the National Natural Science Foundation of China (NSFC 30870802, 81171043).
    Introduction The neurohormones arginine vasopressin (AVP) and oxytocin (OT) perform homeostatic functions for water balance and reproduction. Structurally similar, differing by only two amino acids, AVP and OT are mainly derived from preprohormones synthesized by magnocellular neurons (MCNs) in the paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus (Hth), and are secreted from the posterior pituitary (the neurohypophysis; NH) into the general circulation, where they exert their multiple effects. It is generally believed that regulation of AVP and/or OT release occurs in both the somatodendritic regions in the hypothalamus and the nerve terminal regions in the neurohypophysis and involves both neuron–neuron and neuronal–glial cell interactions (Hussy, 2002, Landgraf, Neumann, 2004, Panatier, 2009, Son et al, 2013, Tobin et al, 2012). Numerous neuromodulators of the central nervous system (CNS) can modify the mechanisms involved in AVP/OT synthesis and release (Bojanowska et al, 1999, Chu et al, 2009, Ciosek, Drobnik, 2013, Ciosek, Izdebska, 2009, Iovino et al, 2012, Juszczak et al, 2007, Sladek, Kapoor, 2001). Putative modulators include two members of the galanin neuropeptide family: “parental” galanin (Gal) and its cousin galanin-like peptide (GALP).