Distinct roles of ASIC3 and TRPV1 receptors in electroacupuncture-induced segmental and systemic analgesia

doi:10.1007/s11684-016-0482-7

Front. Med.

2016, Vol. 10

Issue (4) : 465-472 https://doi.org/10.1007/s11684-016-0482-7

RESEARCH ARTICLE

Distinct roles of ASIC3 and TRPV1 receptors in electroacupuncture-induced segmental and systemic analgesia

Juanjuan Xin,Yangshuai Su,Zhaokun Yang,Wei He,Hong Shi,Xiaoyu Wang,Ling Hu,Xiaochun Yu,Xianghong Jing(

),Bing Zhu(

)

Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700, China

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Abstract

Previous studies have demonstrated the effects of different afferent fibers on electroacupuncture (EA)-induced analgesia. However, contributions of functional receptors expressed on afferent fibers to the EA analgesia remain unclear. This study investigates the roles of acid-sensing ion channel 3 (ASIC3) and transient receptor potential vanilloid 1 (TRPV1) receptors in EA-induced segmental and systemic analgesia. Effects of EA at acupoint ST36 with different intensities on the C-fiber reflex and mechanical and thermal pain thresholds were measured among the ASIC3⁻^/⁻, TRPV1⁻^/⁻, and C57BL/6 mice. Compared with C57BL/6 mice, the ipsilateral inhibition of EA with 0.8 C-fiber threshold (0.8Tc) intensity on C-fiber reflex was markedly reduced in ASIC3⁻^/⁻ mice, whereas the bilateral inhibition of 1.0 and 2.0Tc EA was significantly decreased in TRPV1⁻^/⁻ mice. The segmental increase in pain thresholds induced by 0.3 mA EA was significantly reduced in ASIC3⁻^/⁻ mice, whereas the systemic enhancement of 1.0 mA EA was markedly decreased in TRPV1⁻^/⁻ mice. Thus, segmental analgesia of EA with lower intensity is partially mediated by ASIC3 receptor on Aβ-fiber, whereas systemic analgesia induced by EA with higher intensity is more likely induced by TRPV1 receptor on Ad- and C-fibers.

Keywords electroacupuncture analgesia ASIC3 TRPV1 C-fiber reflex

Corresponding Author(s): Xianghong Jing,Bing Zhu

Just Accepted Date: 08 November 2016 Online First Date: 28 November 2016 Issue Date: 01 December 2016

Cite this article:

Juanjuan Xin,Yangshuai Su,Zhaokun Yang, et al. Distinct roles of ASIC3 and TRPV1 receptors in electroacupuncture-induced segmental and systemic analgesia[J]. Front. Med., 2016, 10(4): 465-472.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-016-0482-7
https://academic.hep.com.cn/fmd/EN/Y2016/V10/I4/465

Fig.1 Inhibition of C-fiber reflex response induced by 0.8Tc EA at ipsilateral or contralateral ST36 among three groups of mice. The typical individual example showing the inhibitions of 0.8 Tc EA at ipsilateral (A) and contralateral (B) ST36, respectively, on the EMG responses induced by the stimulation of sural nerve. The traces from top to bottom are: control and the post-EA effects on the EMG response induced by C-fiber activation recorded from 0 to 5 min (P0', P1', P2', P3', P4', and P5′, corresponding to six post-EA effects recorded in a successive 5 min after stimulation with an interval of 1 min) after EA stimulation. The controls (Con.) were presented as 100%, and the depression on C-fiber reflex of 0.8 Tc EA at different time points were presented as percentage of the controls. Compared with C57BL/6, the inhibitory effects on C-fiber reflex response induced by 0.8 Tc EA at ipsilateral ST36 in ASIC3^-^/^- mice were significantly reduced (C). The 0.8 Tc EA at contralateral ST36 had no effect on the C-fiber reflex (D). The results are expressed as mean±SE. **P<0.01, ***P<0.001, as compared with the controls. ^##P<0.01, ^###P<0.001, as compared with those in C57BL/6 mice.

Fig.2 Inhibition of C-fiber reflex response induced by 1.0 Tc EA at ipsilateral or contralateral ST36 among three groups of mice. The typical individual example showing the inhibitions of 1.0 TcEA at ipsilateral (A) and contralateral (B) ST36 respectively, on the EMG responses induced by the stimulation of sural nerve. The 1.0 Tc EA at ipsilateral or contralateral ST36 produced significant inhibitory effects on the C-fiber reflex, which were markedly lower in TRPV1^-^/^- mice compared with those in C57BL/6 mice (C, D). The results are expressed as mean±SE. *P<0.05, **P<0.01, ***P<0.001, as compared with the controls. ^###P<0.001, as compared with those in C57BL/6 mice.

Fig.3 Inhibition of C-fiber reflex response induced by 2.0 Tc EA at ipsilateral or contralateral ST36 among the three groups of mice. The typical individual example showing the inhibitions of 2.0 Tc EA at ipsilateral (A) and contralateral (B) ST36, respectively, on the EMG responses induced by the stimulation of sural nerve. The 2.0 Tc EA at ipsilateral or contralateral ST36 produced significant inhibitory effects on the C-fiber reflex, which were markedly lower in TRPV1^-^/^- mice compared with those in C57BL/6 mice (C, D). The results are expressed as mean±SE. *P<0.05, **P<0.01, ***P<0.001, as compared with the controls. ^##P<0.01, ^###P<0.001, as compared with those in C57BL/6 mice.

Fig.4 Increases in the mechanical and thermal withdrawal latency of ipsilateral and contralateral hindpaw respectively, produced by distinct EA stimulation (0.3 or 1 mA) at ST36 in C57BL/6 (A, B), ASIC3^-^/^- (C, D) and TRPV1^-^/^- (E, F) mice. The analgesic effects of 0.3 mA EA were ipsilateral. Furthermore, it has no impact on the ipsilateral pain threshold in ASIC3^-^/^- mice. The 1.0 mA EA produced significant enhancements in bilateral pain threshold. The results are expressed as mean±SE. *P< 0.05, **P<0.01, ***P<0.001 as compared with the basal level pre-EA stimulation.

Fig.5 Comparison of the analgesic effects by distinct EA stimulation among C56BL/6, ASIC3^-^/^-, and TRPV1^-^/^- mice. Compared with C56BL/6 mice, the increases in ipsilateral mechanical (A) and thermal (C) pain thresholds induced by 0.3 mA EA in ASIC3^-^/^- were significantly lower, whereas the bilateral analgesic effects of 1 mA (B, D) EA on TRPV1^-^/^- were markedly decreased. The results are expressed as mean±SE. *P<0.05, as compared with those in C57BL/6 mice.

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