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      GABAergic Inhibition of Spinal Cord Dorsal Horns Contributes to Analgesic Effect of Electroacupuncture in Incisional Neck Pain Rats

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          Abstract

          Background

          Acupuncture has shown to be effective in relieving post-surgical pain. Nonetheless, its underlying mechanisms remain largely unknown. In the present study, we investigated the effect of electroacupuncture (EA) on the expression of GABA, GABA-A receptor (R) and GABA-BR in the spinal cord dorsal horns (DHs), and the involved neural cells in rats with incisional neck pain.

          Materials and Methods

          Male SD rats were randomly divided into control, model, Futu (LI18), Hegu-Neiguan (LI4-PC6), and Zusanli-Yanglingquan (ST36-GB34) groups. The incisional neck pain model was established by making a longitudinal incision and repeated mechanical separation along the thyroid gland region. EA (2Hz/100Hz, 1mA) was applied to LI18, LI4-PC6, ST36-GB34 separately for 30min, once at 4, 24 and 48h after incision. The local thermal pain threshold (TPT) of the focus was measured and the expression of GABA, and GABAR proteins and mRNAs detected by immunofluorescence stain and quantitative RT-PCR, respectively.

          Results

          The analgesic effect of LI18 and LI4-PC6 was superior to that of ST36-GB34 in incisional neck pain rats. Moreover, the EA stimulation of LI18 or LI4-PC6 increased the expression of GABA and GABA-Aα2 and GABA-Aβ3, GABA-B1, and GABA-B2 mRNAs in spinal DHs 4h after surgery, while GABA-A and GABA-B antagonists inhibited the analgesic effect of LI18. Immunofluorescence double staining showed that GABA was expressed on astrocytes and neurons, and GABA-B expressed only on neurons.

          Conclusion

          EA of both LI18 and LI4-PC6 has a good analgesic effect in incisional neck pain rats, which is closely related to their effects in upregulating the expression of GABA and its receptors in spinal DHs. The effects of LI18 and LI4-PC6 EA are obviously better that those of ST36-GB34 EA, and GABA is expressed on neurons and astrocytes.

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          Most cited references 43

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          Effects of intrathecally administered THIP, baclofen and muscimol on nociceptive threshold.

          This study examined whether the antinociceptive activity of THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), a GABA agonist, is mediated through an action exerted at the level of the spinal cord. Intrathecal injection of doses of THIP devoid of motor effects (1-2 micrograms) did not increase tail flick or hot plate latencies in the rat. Although hot plate latency was transiently increased by intrathecal injection of 5 micrograms THIP, slight motor impairment was observed at this dose. Higher doses of THIP (15-50 micrograms) produced flaccidity of the hindlimbs. Intrathecal injection of low doses of muscimol (0.25 microgram) that did not produce motor impairment increased tail flick, but not hot plate, latencies. Baclofen produced motor incoordination following intrathecal injection of 10 micrograms; however, intrathecal injection of 1 microgram significantly increased both tail flick and hot plate latencies without attendant motor effects. Thus, baclofen was the only compound in which the antinociceptive effect was clearly distinguished from the motor effect. These results additionally indicate that the spinal cord does not mediate the antinociceptive activity of THIP.
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            The Efficacy of Acupuncture in Post-Operative Pain Management: A Systematic Review and Meta-Analysis

            Background Postoperative pain resulting from surgical trauma is a significant challenge for healthcare providers. Opioid analgesics are commonly used to treat postoperative pain; however, these drugs are associated with a number of undesirable side effects. Objective This systematic review and meta-analysis evaluated the effectiveness of acupuncture and acupuncture-related techniques in treating postoperative pain. Data Source MEDLINE, Cochrane Library, and EMBASE databases were searched until Sep 30, 2014. Study Eligibility Criteria Randomized controlled trials of adult subjects (≥ 18 years) who had undergone surgery and who had received acupuncture, electroacupuncture, or acupoint electrical stimulation for managing acute post-operative pain were included. Results We found that patients treated with acupuncture or related techniques had less pain and used less opioid analgesics on Day 1 after surgery compared with those treated with control (P < 0.001). Sensitivity analysis using the leave-one-out approach indicated the findings are reliable and are not dependent on any one study. In addition, no publication bias was detected. Subgroup analysis indicated that conventional acupuncture and transcutaneous electric acupoint stimulation (TEAS) were associated with less postoperative pain one day following surgery than control treatment, while electroacupuncture was similar to control (P = 0.116). TEAS was associated with significantly greater reduction in opioid analgesic use on Day 1 post surgery than control (P < 0.001); however conventional acupuncture and electroacupuncture showed no benefit in reducing opioid analgesic use compared with control (P ≥ 0.142). Conclusion Our findings indicate that certain modes of acupuncture improved postoperative pain on the first day after surgery and reduced opioid use. Our findings support the use of acupuncture as adjuvant therapy in treating postoperative pain.
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              GABA decreases in the spinal cord dorsal horn after peripheral neurectomy.

              A significant fall in the number of GABA-immunoreactive cells in laminae I-III of the rat spinal cord occurred in the somatotopic area of projection of the sciatic nerve after nerve transection. The decrease started at 2 weeks post-neurectomy, and at 4 weeks ipsilateral mean cell numbers were approximately 72% of contralateral control values. Similarly, the concentration of GABA in spinal homogenates was significantly reduced 4 weeks post-neurectomy. These data, together with our recent finding of an increase in spinal GABA during chronic inflammation of the hindlimb, suggest that the level of GABA in the dorsal horn is regulated by the amount of primary afferent input.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                JPR
                jpainres
                Journal of Pain Research
                Dove
                1178-7090
                03 July 2020
                2020
                : 13
                : 1629-1645
                Affiliations
                [1 ]Department of Physiology, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences , Beijing 100700, People’s Republic of China
                [2 ]Laboratory for Architecture of Acupoints, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences , Beijing 100700, People’s Republic of China
                Author notes
                Correspondence: Jun-ling Liu; Jun-ying Wang Tel +86-10-64089409; +86-10-64089419 Email 13521898023@163.com; wjyanguning@aliyun.com
                Article
                242330
                10.2147/JPR.S242330
                7340366
                © 2020 Wang et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 10, References: 48, Pages: 17
                Categories
                Original Research

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