Electroacupuncture Alleviates Dry Eye Ocular Pain Through TNF-ɑ Mediated ERK1/2/P2X3R Signaling Pathway in SD Rats

J Pain Res. 2023 Dec 12:16:4241-4252. doi: 10.2147/JPR.S436258. eCollection 2023.

Abstract

Purpose: This study aimed to examine electroacupuncture's influence on ocular pain and its potential modulation of the TNF-ɑ mediated ERK1/2/P2X3R signaling pathway in dry eye-induced rat models.

Methods: Male Sprague-Dawley rats with induced dry eye, achieved through extraorbital lacrimal gland removal, were treated with electroacupuncture. Comprehensive metrics such as the corneal mechanical perception threshold, palpebral fissure height, eyeblink frequency, eye wiping duration, behavioral changes in the open field test, and the forced swimming test were employed. Additionally, morphological changes in microglia and neurons were observed. Expression patterns of key markers, TNF-ɑ, TNFR1, p-ERK1/2, and P2X3R, in the trigeminal ganglion (TG) and spinal trigeminal nucleus caudalis (SpVc) regions, were studied with etanercept serving as a control to decipher the biochemistry of electroacupuncture's therapeutic effects.

Results: Electroacupuncture treatment demonstrated a notable decrease in the corneal mechanical perception threshold, improvement in palpebral fissure height, and significant reductions in both eyeblink frequency and eye wiping duration. Moreover, it exhibited a promising role in anxiety alleviation. Notably, the technique effectively diminished ocular pain by curbing microglial and neuronal activation in the TG and SpVc regions. Furthermore, it potently downregulated TNF-ɑ, TNFR1, p-ERK1/2, and P2X3R expression within these regions.

Conclusion: Electroacupuncture attenuated damage to sensory nerve pathways, reduced pain, and eased anxiety in dry eye-afflicted rats. The findings suggest a crucial role of TNF-ɑ mediated ERK1/2/P2X3R signaling pathway inhibition by electroacupuncture in these benefits.

Keywords: ERK1/2/P2X3R signaling pathway; TNF-ɑ; dry eye; electroacupuncture; ocular pain.

Grants and funding

This study was supported by the National Natural Science Foundation of China [No. 82074526; Nanjing, China] and the Postgraduate Research & Practice Innovation Program of Jiangsu Province [No. KYCX23_2138; Nanjing, China].