Veratramine ameliorates pain symptoms in rats with diabetic peripheral neuropathy by inhibiting activation of the SIGMAR1-NMDAR pathway.

Abstract

CONTEXT:

Veratramine may have a potential therapeutic effect for diabetic peripheral neuropathy (DPN).

OBJECTIVE:

To evaluate whether veratramine ameliorates neuropathic pain in a rat diabetic model.

MATERIALS AND METHODS:

Sprague-Dawley rats were used for a diabetic model induced by a streptozotocin + high-fat diet. Two months after the induction of the diabetic model, the rats with DPN were screened according to the mechanical pain threshold. The rats with DPN were divided into a model group (n = 12) and a treated group (n = 12). Rats with diabetes, but without peripheral neuropathy, were used in the vehicle group (n = 9). The treatment group received 50 μg/kg veratramine via the tail vein once a day for 4 weeks. During modelling and treatment, rats in all three groups were fed a high-fat diet.

RESULTS:

The mechanical withdrawal threshold increased from 7.5 ± 1.9 N to 17.9 ± 2.6 N in DPN rats treated with veratramine. The tolerance time of the treated group to hot and cold ectopic pain increased from 11.8 ± 4.2 s and 3.4 ± 0.8 s to 20.4 ± 4.1 s and 5.9 ± 1.7 s, respectively. Veratramine effectively alleviated L4-L5 spinal cord and sciatic nerve pathological injury. Veratramine inhibited the expression of SIGMAR1 and the phosphorylation of the N-methyl-d-aspartate receptor (NMDAR) Ser896 site in spinal cord tissue, as well as inhibited the formation of SIGMAR1-NMDAR and NMDAR-CaMKII complexes.

DISCUSSION AND CONCLUSIONS:

Veratramine may alleviate the occurrence of pain symptoms in rats with DPN by inhibiting activation of the SIGMAR1-NMDAR pathway.

• Authors: Yu Zhang, Guangyao Ye, Yuebo Chen, Chaoxu Sheng, Jianlin Wang, Lingsi Kong, Liyong Yuan, Chunyan Lin
• Journal: Pharmaceutical biology (Pharm Biol) Vol. 60 Issue 1 Pg. 2145-2154 (Dec 2022) ISSN: 1744-5116 [Electronic] England
• PMID: 36373991 (Publication Type: Journal Article)

Chemical References

• Receptors, N-Methyl-D-Aspartate
• veratramine

Topics

• Animals
• Rats
• Diabetes Mellitus
• Diabetic Neuropathies (drug therapy)
• Neuralgia (drug therapy)
• Peripheral Nerve Injuries
• Rats, Sprague-Dawley
• Receptors, N-Methyl-D-Aspartate (metabolism)