Int J Med Sci 2018; 15(9):953-960. doi:10.7150/ijms.24146

Research Paper

Manual acupuncture relieves bile acid-induced itch in mice: the role of microglia and TNF-α

Yu-Chen Lee1,2#, Chia-Hsien Lin3#, Shih-Ya Hung4, Hsin-Yi Chung2, Sih-Ting Luo2, Iona MacDonald2, Yu-Ting Chu2, Pei-Lin Lin5✉, Yi-Hung Chen2,6,7✉

1. Department of Acupuncture, China Medical University Hospital, Taichung 40402, Taiwan
2. Graduate Institute of Acupuncture Science, China Medical University, Taichung 40402, Taiwan
3. Department of Health Industry Management, Kainan University, No. 1 Kainan Road, Taoyuan 33857, Taiwan
4. Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 40402, Taiwan
5. Department of Anesthesiology, National Taiwan University Hospital, Taipei 10002, Taiwan
6. Chinese Medicine Research Center, China Medical University, Taichung 40402, Taiwan
7. Department of Photonics and Communication Engineering, Asia University, Taiwan
#: equal contribution

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
Lee YC, Lin CH, Hung SY, Chung HY, Luo ST, MacDonald I, Chu YT, Lin PL, Chen YH. Manual acupuncture relieves bile acid-induced itch in mice: the role of microglia and TNF-α. Int J Med Sci 2018; 15(9):953-960. doi:10.7150/ijms.24146. Available from

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Pruritus, or itch, is a frequent complaint amongst patients with cholestatic hepatobiliary disease and is difficult to manage, with many patients refractory to currently available antipruritic treatments. In this study, we examined whether manual acupuncture (MA) at particular acupoints represses deoxycholic acid (DCA)-induced scratching behavior and microglial activation and compared these effects with those induced by another pruritogen, 5'-guanidinonaltrindole (GNTI, a kappa opioid receptor antagonist). MA at Hegu (LI4) and Quchi (LI11) acupoints significantly attenuated DCA- and GNTI-induced scratching, whereas no such effects were observed at the bilateral Zusanli acupoints (ST36). Interestingly, GNTI-induced scratching was reduced similarly by both MA and electroacupuncture (EA) at the LI4 and LI11 acupoints. MA at non-acupoints did not affect scratching behavior. Intraperitoneal injection of minocycline (a microglial inhibitor) reduced GNTI- and DCA-induced scratching behavior. In Western blot analysis, subcutaneous DCA injection to the back of the neck increased spinal cord expression of ionized calcium-binding adapter molecule 1 (Iba1) and tumor necrosis factor-alpha (TNF-α) as compared with saline injection, while MA at LI4 and LI11 reduced these DCA-induced changes. Immunofluorescence confocal microcopy revealed that DCA-induced Iba1-positive cells with thicker processes emanated from the enlarged cell bodies, while this effect was attenuated by pretreatment with MA. It is concluded that microglia and TNF-α play important roles in the itching sensation and MA reduces DCA-induced scratching behavior by alleviating spinal microglial activation. MA may be an effective treatment for cholestatic pruritus.

Keywords: acupuncture, pruritogen, microglial activation, spinal cord, cholestatic pruritus