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The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice

The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice

Published on: July 16, 2014

The peripheral PI3K/AKT/MLC signalling pathway alleviates myofascial pain in rats by inhibiting abnormal contraction

Mingyang Zhang^1,2, Yuchang Zhu³, Feihong Jin⁴

¹The Affiliated Taian City Central Hospital of Qingdao University, Taian, Shandong, China.

|August 26, 2025

Abstract

Background:

Myofascial trigger points (MTrPs) for abnormal skeletal muscle contraction are the cause of myofascial pain. The G protein-coupled receptor family and tyrosine kinase receptor family regulate the contraction of vascular smooth muscle through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway. Phosphorylated myosin light chain (p-MLC) is associated with skeletal muscle contraction. The aim of the current study was to explore the effect and mechanism of the PI3K/AKT/MLC signalling pathway on myofascial pain in rats.

Methods:

A rat model of myofascial pain was established by a blunt strike to the gastrocnemius muscle combined with centrifugal exercise for 8 weeks, followed by recovery for 4 weeks. Different concentrations of the PI3K inhibitor LY294002 (0.01, 0.1, or 1 mg/ml) were subsequently injected into the MTrPs of rats with myofascial pain to observe the effects on the mechanical tenderness threshold at the MTrPs.

Results:

LY294002 (0.1 mg/ml) inhibited myofascial pain at 0.5, 1 and 2 h after injection, and LY294002 (1 mg/ml) inhibited myofascial pain at 0.5, 1, 2 and 4 h after injection. The expression of PI3K increased on the enlarged muscle fibre membrane at MTrPs. LY294002 (1 mg/ml) inhibited the expression of PI3K, p-AKT, and p-MLC and the abnormal contraction of muscle fibres at MTrPs and alleviated nerve fibre compression at MTrPs. Moreover, LY294002 inhibited the expression of Fos in the spinal dorsal horn of rats with myofascial pain.

Conclusions:

These findings suggested that the increased expression of PI3K/p-AKT/p-MLC was related to myofascial pain in rats and that the PI3K inhibitor LY294002 might alleviate myofascial pain in rats by inhibiting abnormal contraction at MTrPs.

Keywords:

LY294002 PI3K myofascial pain syndrome myofascial trigger points

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