Does acute-phase acupuncture at Hegu (LI04) promote facial nerve regeneration and upregulation of the PI3K/Akt/mTOR pathway? A hypothesis-generating study in a rabbit crush injury model.

Abstract

This study used the rabbit facial nerve crush injury model to investigate the time-dependent effects of acupuncture at Hegu (LI04) on facial nerve regeneration and regulatory role of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway. Thirty-two New Zealand rabbits with facial nerve crush injury were randomly assigned to four groups (n = 8 each): sham-operated, model, acute-phase acupuncture (treatment initiated immediately after modeling, daily for 10 days), and chronic-phase acupuncture (treatment initiated 7 days after modeling, daily for 10 days). Simone's 10-point scale was used for behavioral assessment on day 1 and day 17 post-modeling. Hematoxylin & Eosin staining was used for histomorphology analysis. PI3K, Akt, and mTOR protein and mRNA expression levels were assessed by immunohistochemistry and RT-qPCR, respectively. Both acute- and chronic-phase acupuncture interventions significantly improved the facial nerve function scores, reduced myelin sheath edema, and upregulated the expression levels of PI3K, Akt, and mTOR compared to the model group. Compared to the chronic-phase intervention, the acute-phase intervention yielded superior functional recovery, more regular nerve fiber arrangement, and stronger upregulation of PI3K, Akt, and mTOR proteins and mRNAs. In this experimental model, acupuncture at Hegu (LI04) was associated with improved repair of facial nerve crush injury, with acute-phase intervention showing greater efficacy than chronic-phase intervention. This time-dependent effect was accompanied by upregulation of the PI3K/Akt/mTOR signaling pathway, suggesting a potential association. However, given the substantial methodological limitations-including the absence of sham controls, lack of electrophysiological validation, and the partial nature of the injury model-these findings provide preliminary experimental evidence that may help inform the design of future clinical studies, rather than serving as confirmatory evidence.