Effect of ropivacaine on peripheral neuropathy in streptozocin diabetes-induced rats through TRPV1-CGRP pathway.

Nanwen Zhang,Kai Yu,Xiaole Chen,Weifang Wu,Yuan Chen,Haixiang Wei,Shan Lin,Jianming Lin,Yanqi Cui,Yize Bian,Peimin Lin,Zhiwei Liu,Renwei Luo,Honglin Wang

doi:10.1042/bsr20190817

Nanwen Zhang, Kai Yu + Show 12 more

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https://doi.org/10.1042/bsr20190817

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Abstract

Objective To determine the effect of ropivacaine on peripheral neuropathy in diabetic rats and its possible mechanism.Methods Forty-eight Sprague–Dawley rats were randomly divided into six groups: nondiabetic control group, nondiabetic group A (0.25% ropivacaine), nondiabetic group B (0.75% ropivacaine), diabetic control group (diabetic peripheral neuropathy (DPN) +artificial cerebrospinal fluid), diabetic group A (DPN+0.25% ropivacaine), and diabetic group B (DPN + 0.75% ropivacaine), with eight rats in each group. Within an hour of the last administration, the sciatic motor nerve conduction velocity (MNCV) of each group was measured, and the morphological changes of rat sciatic nerve were observed by HE, Weil’s staining and electron microscopy. The expression of transient receptor potential vanilloid (TRPV1) in the spinal cord dorsal horn of rats was analyzed by immunohistochemistry, and the expression of Calcitonin gene-related peptide (CGRP) protein in the spinal cord was analyzed by Western blot.Results Compared with the nondiabetic control group, elevated blood glucose, decreased weight and reduced average mechanical withdrawal threshold (MWT), additionally, the sciatic nerves showed significantly slowed conduction velocity (both P<0.001) and damaged pathological structure, the expression of TRPV1 and CGRP were decreased (both P<0.001) in the diabetic groups. Compared with the diabetic control group, down-regulation of TRPV1 and CGRP in spinal cord was significant for the diabetic groups A and B treated with 0.25 and 0.75% ropivacaine, the higher concentration of ropivacaine correlated with a greater change.Conclusion Ropivacaine can significantly block sciatic nerve conduction velocity in DPN rats in a concentration-dependent manner, which may be related to the expression of the TRPV1-CGRP pathway.

Highlights

Diabetic peripheral neuropathy (DPN) is the most common complication of type 1 and 2 diabetes
We evaluated the change between the pre-model base measurement and measurements made 2, 4 and 8 weeks after diabetes mellitus (DM) model establishment
The rats in the diabetic group exhibited a high level of blood glucose on 14 days (2 weeks), 28 days (4 weeks), and 56 days (8 weeks) compared with the levels in the nondiabetic groups measured at the same time (P

Summary

Introduction

Diabetic peripheral neuropathy (DPN) is the most common complication of type 1 and 2 diabetes. DPN is defined as the presence of symptoms and/or signs of peripheral nerve dysfunction in diabetic patients after the exclusion of other causes [1]. Anesthetic management of these patients is more challenging, with more frequent difficulties in airway control, association with myocardial dysfunction and renal disease, and the occurrence of perioperative dysglycemia. CGRP has strong biological activity, acting as an important neurotransmitter in both the central and peripheral nervous systems (CNS and PNS) [3,4]. By coupling G protein to transmit signals into cells through cAMP, CGRP is key to many physiological effects, making it an active participant in the development and progression of DM, pain, inflammation, and other diseases or disease-related symptoms

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