Abstract

Acupuncture can significantly ameliorate inflammatory pain in acute visceral hyperalgesia. Hyperalgesia is attenuated by inflammatory mediators that activate transient receptor potential vanilloid 1 (TRPV1), and TRPV1 is regulated by nerve growth factor (NGF)-induced phosphatidylinositol 3-kinase (PI3K)/Akt pathway. However, it is unknown whether NGF-induced PI3K/Akt pathway is associated with manual acupuncture (MA). In this study, the effect and mechanism of MA at Shangjuxu (ST37) and Quchi (LI11) were examined using an acetic acid-induced rat model with visceral hyperalgesia. We demonstrated that MA at ST37 significantly decreased abdominal withdrawal reflex (AWR) scores, proinflammatory cytokine expression (TNF-α, IL-1β, and IL-6), and TRPV1 protein and mRNA expression in rats with acute visceral hyperalgesia compared with the untreated controls, while MA at LI11 showed no effect. The effects of MA at ST37 were reversed after treatment with the PI3K agonist IGF-1 30 min before MA. In rats with visceral hyperalgesia, the upregulation of NGF, tropomyosin-receptor-kinase A (TrkA), PI3K, and phosphorylation-Akt (p-Akt) was decreased by MA at ST37, indicating that TRPV1 regulation via the NGF-induced PI3K/Akt pathway plays a vital role in the effects of MA-mediated amelioration of acute visceral hyperalgesia.

Highlights

  • Visceral pain is a common type of pain caused by underlying disease, for which patients frequently seek medical intervention

  • manual acupuncture (MA) at the LI11 point showed no significant effects compared to the model group (P > 0.05), and significant differences were observed between the LI11 and ST37 group (P < 0.05)

  • The effects of MA at ST37 were inhibited by the administration of the phosphatidylinositol 3-kinase (PI3K) agonist IGF-1; the ST37 + IGF-1 group showed significant differences when compared to the ST37 group (P < 0.05), but not the IGF-1 group (P > 0.05; Figure 2)

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Summary

Introduction

Visceral pain is a common type of pain caused by underlying disease, for which patients frequently seek medical intervention. E most common drugs currently used to treat acute and chronic visceral pain disorders include analgesics, antispasmodics, and antidepressants. These are frequently associated with adverse effects such as addiction and constipation [3]. Acupuncture, a traditional Chinese treatment, has been used in the clinic to improve visceral functions [4] and ameliorate acute [5,6,7] and chronic [8,9,10,11] pain. Previous research studies found that the treatment effect of ST37 on the ulcerative colitis is better than LI11 in improving the ulcer score, whose mechanism is underlying alleviation of tumor necrosis factor (TNF)-α and increasing the levels of choline acetyltransferase (ChAT) and alpha 7 nicotinic acetylcholine receptor (α7nAChR) [20]

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