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Galanin receptor 1 plays an antinociceptive effect via inhibiting PKA activation in the nucleus accumbens of rats with neuropathic pain
Y. Zhang, Y. Gao, C. Y. Li, W. Dong, Y. Dong, M. N. Li, Y. N. Liu, S. L. Xu
Language English Country Czech Republic
Document type Journal Article
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- MeSH
- Enzyme Activation drug effects physiology MeSH
- Analgesics metabolism MeSH
- Bradykinin analogs & derivatives pharmacology MeSH
- Galanin analogs & derivatives pharmacology MeSH
- Rats MeSH
- Pain Measurement drug effects methods MeSH
- Neuralgia metabolism prevention & control MeSH
- Nucleus Accumbens drug effects metabolism MeSH
- Peptide Fragments pharmacology MeSH
- Rats, Sprague-Dawley MeSH
- Cyclic AMP-Dependent Protein Kinases antagonists & inhibitors metabolism MeSH
- Receptor, Galanin, Type 1 agonists antagonists & inhibitors biosynthesis MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
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 14(th) and 28(th) 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.
Department of Physiology School of Basic Medicine Kunming Medical University Kunming China
Department of Tumor 4th Affiliated Hospital Kunming Medical University Kunming China
References provided by Crossref.org
Literatura
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- $a 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 14(th) and 28(th) 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.
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