The inhibitory effect of Phα1ß toxin on diabetic neuropathic pain involves the CXCR4 chemokine receptor.
Pharmacol Rep
; 72(1): 47-54, 2020 Feb.
Article
en En
| MEDLINE
| ID: mdl-32016848
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 Phα1ß, 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 Phα1ß 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. Phα1ß (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: Phα1ß, 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 Phα1ß or AMD-3100, while ω-conotoxin MVIIA did not affect. The inhibitory effects of Phα1ß on PDN may involve voltage-dependent calcium channels.
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Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Venenos de Araña
/
Diabetes Mellitus Experimental
/
Neuropatías Diabéticas
/
Analgésicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Pharmacol Rep
Asunto de la revista:
FARMACOLOGIA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Brasil