IMR Press / FBL / Volume 26 / Issue 5 / DOI: 10.52586/4919
Open Access Article
Analgesic effect of dl-THP on inflammatory pain mediated by suppressing spinal TRPV1 and P2X3 receptors in rats
Yan Wang1,2,†Rui-Rui Wang1,2,†Wei Sun1,2,†Chao Lou3Fan Yang1,2Ting He1,2Xiao-Liang Wang1,2Fa-Le Cao4,*Jun Chen1,2,*
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1 Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, 710038 Xi’an, China
2 Key Laboratory of Brain Stress and Behavior, PLA, 710038 Xi’an, China
3 Department of Genetics, Northwest Women’s and Children’s Hospital, 710032 Xi’an, China
4 The Department of Neurology, The 960th Hospital of PLA, 271000 Tai’an, China

These authors contributed equally.

Front. Biosci. (Landmark Ed) 2021, 26(5), 1–10; https://doi.org/10.52586/4919
Submitted: 3 March 2020 | Accepted: 1 February 2021 | Published: 30 April 2021
Copyright: © 2021 The Author(s). Published by BRI.
This is an open access article under the CC BY 4.0 license (https://creativecommons.org/licenses/by/4.0/).
Abstract

Tetrahydropalmatine (dl-THP) demonstrates an analgesic effect in animal models of neuropathic and inflammatory pain, however, the underlying mechanisms of its pharmacological action within the spinal cord remains unclear. Both P2X3 receptor and TRPV1 are associated with the development and progression of such neuropathic and inflammatory pain. Here, we found that both pre-treatment and post-treatment with dl-THP could attenuate Bee Venom (BV)-induced persistent spontaneous pain-related behaviors in rats. Further, the dl-THP also exerted both preventive and therapeutic analgesic effects in BV-induced primary thermal and mechanical pain hypersensitivity as well as in mirror-image thermal pain hypersensitivity. The Rota-Rod treadmill test revealed that the dl-THP administration did not alter the rats’ motor coordinating performance. The TRPV1 and P2X3 receptor proteins increased markedly in the spinal cord of the rats following s.c. BV injection, which was significantly suppressed by dl-THP. These results suggest that dl-THP exerts a robust antihyperalgesia effect through down-regulation of P2X3 receptors and TRPV1 in inflammatory pain, providing a scientific basis for the translation of dl-THP treatment in clinics.

Keywords
Inflammatory pain
dl-THP
TRPV1
P2X3 receptor
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