Effects of Duloxetine on the Toll-Like Receptor 4 Signaling Pathway in Spinal Dorsal Horn in a Rat Model of Diabetic Neuropathic Pain.
Pain Med
; 19(3): 580-588, 2018 03 01.
Article
en En
| MEDLINE
| ID: mdl-28575508
ABSTRACT
Objective:
Although duloxetine has been approved for clinical therapy for diabetic peripheral neuropathic pain, the exact mechanism underlying the anti-allodynic effects in rat models of diabetes mellitus remains obscure. We attempted to identify whether duloxetine exerts anti-allodynic effects via inhibition of the TLR4-Myd88-dependent pathway in diabetic neuropathic pain (DNP) rats.Methods:
An animal model of type 1 diabetic neuropathic pain was induced by intraperitoneal streptozotocin in 108 rats randomized into four groups control, DNP, solvent control + DNP, and DNP + duloxetine. The DNP model establishment was validated, providing the MWT and TWL measurements were less than 80% of the baseline value on d14 after streptozotocin administration. The expressions of TLR4, Myd88, and NF-κB in the spinal dorsal horn were determined 21 days after streptozotocin injection by immunohistochemical assay and Western blot.Results:
The results revealed that MWT and TWL in DNP, SC + DNP, and DLX + DNP groups were significantly decreased 14 days after STZ administration vs control (P < 0.05), while the pain thresholds in the DLX + DNP group were partially reversed. The expressions of TLR4, Myd88, and NF-κB in groups C, DNP, and SC + DNP were significantly increased, whereas duloxetine administration significantly downregulated the expressions of TLR4, Myd88, and NF-κB (P < 0.05).Conclusions:
Our findings indicated that duloxetine mitigated mechanical and thermal withdrawal thresholds in STZ-injected rats and rescued the overexpression of the TLR4-Myd88-dependent pathway in the spinal dorsal horn in these rats. Whether these changes directly contributed to the reduction of thermal and mechanical withdrawal behavior needs to be further explored.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Transducción de Señal
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Umbral del Dolor
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Neuropatías Diabéticas
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Receptor Toll-Like 4
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Clorhidrato de Duloxetina
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Analgésicos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2018
Tipo del documento:
Article