Research Article: Dexmedetomidine attenuates P2X4 and NLRP3 expression in the spine of rats with diabetic neuropathic pain1

Date Published: December 20, 2019

Publisher: Sociedade Brasileira para o Desenvolvimento da Pesquisa em Cirurgia

Author(s): Liu Kang, Huang Yayi, Zhou Fang, Zhao Bo, Xia Zhongyuan.

http://doi.org/10.1590/s0102-865020190110000005

Abstract

To evaluate the effects of Dexmedetomidine (Dex) on spinal pathology and inflammatory factor in a rat model of Diabetic neuropathic pain (DNP).

The rats were divided into 3 groups (eight in each group): normal group (N group), diabetic neuropathic pain model group (DNP group), and DNP model with dexmedetomidine (Dex group). The rat model of diabetes was established with intraperitoneal streptozotocin (STZ) injections. Nerve cell ultrastructure was evaluated with transmission electron microscopy (TEM). The mechanical withdrawal threshold (MWT) and motor nerve conduction velocity (MNCV) tests documented that DNP rat model was characterized by a decreased pain threshold and nerve conduction velocity.

Dex restored the phenotype of neurocytes, reduced the extent of demyelination and improved MWT and MNCV of DNP-treated rats (P=0.01, P=0.038, respectively). The expression of three pain-and inflammation-associated factors (P2X4, NLRP3, and IL-IP) was significantly upregulated at the protein level in DNP rats, and this change was reversed by Dex administration (P=0.0022, P=0.0092, P=0.0028, respectively).

The P2X4/NLRP3 signaling pathway is implicated in the development and presence of DNP in vivo, and Dex protects from this disorder.

Partial Text

Diabetic neuropathic pain (DNP) is one of the most frequent chronic complications of diabetes. It is characterized by spontaneous and induced pain, allodynia, and hyperpathia, which result in a decrease in the quality of life of patients affected by DNP1,2. However, the pathologic changes responsible for DNP are not completely understood. Therefore, identification of the molecular mechanisms implicated in DNP pathogenesis would promote the development of effective therapies, reducing complications of diabetes, as well as offering enhanced quality of life for patients with DNP.

All procedures were approved by the Wuhan University Renmin Hospital Animal Ethics Committee.

In this study, we have evaluated the beneficial effects of Dex on DNP in streptozotocin treated rats. We found Dex restored impaired spinal pathology and improved sural nerve structure. In addition, Dex was found to reduce mechanical hyperalgesia and improve the delay of sciatic nerve conduction velocities. Further studies showed that Dex was able to reduce the production of P2X4, IL-1β and NLRP3 levels indicating that Dex holds the ability to protect nerves against inflammatory damage.

The administration of the Dex to DNP model rats restored the neuropathy and improved the pathological development of disease. The present results showed that inflammatory factors mediated by upregulation of P2X4 and NLRP3 are responsible for the development of DNP in the rat model, and Dex alleviated the progress by inhibiting the P2X4/NLRP3 signaling pathway and suppressing the inflammatory response.

 

Source:

http://doi.org/10.1590/s0102-865020190110000005

 

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