Here we used a mouse model of zymosan-induced colorectal hypersensitivity, a similar model of IBS in our previous work, to evaluate the effectiveness of the different number of times of acupuncture and elucidate its potential mechanism of EA treatment. Colorectal distension (CRD) tests show that intracolonic zymosan injection does, while saline injection does not, induce a typical colorectal hypersensitivity. EA treatment at classical acupoints Zusanli (ST36) and Shangjuxu (ST37) in both hind limbs for 15 min slightly attenuated and significantly blunted the hypersensitive responses after first and fifth acupunctures, respectively, to colorectal distention in zymosan treatment mice, but not in saline treatment mice. Western blot results indicated that ion channel and TrpV1 expression in colorectum as well as ERK1/2 MAPK pathway activation in peripheral and central nerve system might be involved in this process. Hence, we conclude that EA is a potential therapeutic tool in the treatment and alleviation of chronic abdominal pain, and the effectiveness of acupuncture analgesia is accumulative with increased number of times of acupuncture when compared to that of a single time of acupuncture.

BackgroundThe hypothalamus is an essential part of the brain that responds to a variety of signaling including stressful stimulations and acupuncture signals. It is also the key element of the hypothalamic-pituitary-adrenal cortex axis(HPAA). The effect of acupuncture is transmitted into the brain from the distance sensory receptor around the acupoints via peripheral nerves and body fluid. In vivo recording the activities of stress reaction neurons (SRNs, CRH-like neurons) in hypothalamic paraventricular nucleus (PVN) in response to the stimulations from different acupoints could therefore objectively reflect the acupuncture afferent effect.MethodsIn this study, the electrophysiological method was adopted to record synchronously the activities of 43 CRH-like neurons after acupuncture stimulations at 33 acupoints located at the different regions. The acupoints that specifically activate certain CRH-like neurons (specificity acupoints) were selected. Furthermore, we investigated in a rat model of unpredictable chronic mild stress (UCMS) whether these specificity acupoints regulate HPAA function. The endpoints of measurement include corticosterone (CORT) level in peripheral blood, the expressions of corticotrophin releasing hormone (CRH) and glucocorticoid receptor (GR) protein in PVN and the animal behavioral performance.ResultsOur results reveal that Shenshu (BL23), Ganshu (BL18), Qimen (LR14), Jingmen (GB25), Riyue (GB24), Zangmen (LR13), Dazui (DU14) and auricular concha region (ACR) are the specificity acupoints; and Gallbladder, Liver and Du Channels were the specificity Channels. The acupoints on Gallbladder Channel and the acupoints innervated by the same spinal cord segments as the adrenal gland demonstrated dramatic effects.ConclusionsThis study provides a new platform to further explore acupoints specificity in the regulation of HPAA activities.

This project was focused on the study of the effect of the different acupoints on visceral hypersensitivity and the correlation with the brain-gut axis. By using a mouse model of zymosan-induced colorectal hypersensitivity, and observing the response of hypersensitivity model to colorectal distension stimulation in acupuncture at different acupoints, we selected the specific acupoints. With immunohistochemical staining method, we observed c-fos expression, distribution and changes after acupuncture on sensory pathway, including colorectum, spinal dorsal horn and different regions of brain center in the model with colorectal distension stimulation, and evaluated the acupuncture effect on brain-gut axis. The results revealed that the effectiveness of acupuncture for alleviating visceral hypersensitivity was different at individual acupoint, meaning Tianshu (ST25), Zusanli (ST36) and Shangjuxu (ST37) > Quchi (LI11) and Dachangshu (BL25) > Ciliao (BL32). C-fos expression was concentrated in anterior cingulate cortex, hypothalamus, spinal dorsal horn and colorectum in model of zymosan-induced colorectal hypersensitivity and it was down-regulated after acupuncture. The results demonstrates that the acupoint specificity presents in acupuncture for relieving visceral hypersensitivity and the effects are more predominated at the acupoints on stomach meridian innervated by the same or adjacent spinal ganglion segments. The model of zymosan-induced colorectal hypersensitivity can be the animal model simulating brain-gut interaction.