The inhibitory efect of Phα1β toxin on diabetic neuropathic pain involves the CXCR4 chemokine receptor.
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2020
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Background: Diabetic neuropathy is a common cause of painful diabetic neuropathy (PDN). C-X-C chemokine receptor type 4 (CXCR4) expression is increased in peripheral nerve samples from diabetes patients, suggesting a role for CXCR4 in PDN. Therefore, we evaluated the effects of Phα1β, ω-conotoxin MVIIA, and AMD3100 in a model of streptozotocin (STZ)-induced PDN in rodents and naïve model of rats with the activation of the CXCR4/stromal cell-derived factor 1 (SDF-1) signal. Methods: Diabetic neuropathy was induced by intraperitoneal (ip) injection of STZ in Wistar rats. Naïve rats were intrathecally injected with SDF-1 to test the CXCR4/SDF-1 signal. The effects of Phα1β intrathecal (it), ω-conotoxin MVIIA intrathecal (it), and AMD3100 intraperitoneal (ip) on rat hypersensitivity, IL-6, and the intracellular calcium [Ca2+]i content of diabetic synaptosomes were studied. Results: The drugs reduced the hypersensitivity in diabetic rats. SDF-1 (1.0 µg/it) administration in naïve rats induced hypersensitivity. Phα1β (100 pmol/it) or AMD3100 (2.5 µg/ip) reduced this hypersensitivity after 2 h treatments, while ω-conotoxin MVIIA did not have an effect. IL-6 and [Ca2+]i content increased in the spinal cord synaptosomes in diabetic rats. The drug treatments reduced IL-6 and the calcium influx in diabetic synaptosomes. Conclusions: Phα1β, ω-conotoxin MVIIA, and AMD3100, after 2 h of treatment of STZ-induced PDN, reduced hypersensitivity in diabetic rats. In naïve rats with CXCR4/SDF-1 activation, the induced hypersensitivity decreased after 2 h treatments with Phα1β or AMD-3100, while ω-conotoxin MVIIA did not affect. The inhibitory effects of Phα1β on PDN may involve voltage-dependent calcium channels.
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ω-Conotoxin MVIIA
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SILVA JÚNIOR, C. A. et al. The inhibitory efect of Phα1β toxin on diabetic neuropathic pain involves the CXCR4 chemokine receptor. Pharmacological Reports, v. 72, p. 47–54, jan. 2020. Disponível em: <https://link.springer.com/article/10.1007/s43440-019-00002-3>. Acesso em: 10 fev. 2020.