Expression and functional characterization of transient receptor potential vanilloid 4 in the dorsal root ganglion and spinal cord of diabetic rats with mechanical allodynia

2020 ◽  
Vol 162 ◽  
pp. 30-39
Author(s):  
Yuan-Yuan Cui ◽  
Meng-Ying Li ◽  
Yu-Ting Li ◽  
Jia-Yi Ning ◽  
Xing-Chun Gou ◽  
...  
2020 ◽  
Vol 21 (12) ◽  
pp. 4341 ◽  
Author(s):  
Yukako Kamata ◽  
Toshie Kambe ◽  
Terumasa Chiba ◽  
Ken Yamamoto ◽  
Kazuyoshi Kawakami ◽  
...  

Painful peripheral neuropathy is a common adverse effect of paclitaxel (PTX) treatment. To analyze the contribution of transient receptor potential vanilloid 1 (TRPV1) in the development of PTX-induced mechanical allodynia/hyperalgesia and thermal hyperalgesia, TRPV1 expression in the rat spinal cord was analyzed after intraperitoneal administration of 2 and 4 mg/kg PTX. PTX treatment increased the expression of TRPV1 protein in the spinal cord. Immunohistochemistry showed that PTX (4 mg/kg) treatment increased TRPV1 protein expression in the superficial layers of the spinal dorsal horn 14 days after treatment. Behavioral assessment using the paw withdrawal response showed that PTX-induced mechanical allodynia/hyperalgesia and thermal hyperalgesia after 14 days was significantly inhibited by oral or intrathecal administration of the TRPV1 antagonist AMG9810. We found that intrathecal administration of small interfering RNA (siRNA) to knock down TRPV1 protein expression in the spinal cord significantly decreased PTX-induced mechanical allodynia/hyperalgesia and thermal hyperalgesia. Together, these results demonstrate that TRPV1 receptor expression in spinal cord contributes, at least in part, to the development of PTX-induced painful peripheral neuropathy. TRPV1 receptor antagonists may be useful in the prevention and treatment of PTX-induced peripheral neuropathic pain.


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