NK cells mediate the cumulative analgesic effect of electroacupuncture in a rat model of neuropathic pain

Gao, Yong Hui; Wang, Jun Ying; Li, Qiao; Chen, Shu-Ping; Tan, Lian-Hong; Xu, Qiuling; Liu, Jun Ling

doi:10.1186/1472-6882-14-316

Cited by 32 publications

(22 citation statements)

References 38 publications

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“…Our finding that two sessions of EA stimulation of both LI18 and LI4-PC6 attenuates the thermal hyperalgesia of the local neck-incision region is similar to our past studies in the same pain model rats [28,29] and in neuropathic pain rats [30]. The LI18 and the thyroid gland region are at the same spinal nerve segment, innervated by the major auricular nerve, superficial cervical nerve, minor occipital nerve, and the accessory nerve.…”

Section: Discussionsupporting

confidence: 76%

Effect of electroacupuncture on the cervicospinal P2X7 receptor/fractalkine/CX3CR1 signaling pathway in a rat neck-incision pain model

Gao

Wang

et al. 2016

Purinergic Signalling

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Increasing evidence supports that acupuncture intervention is an effective approach for intraoperative and postoperative pain. Neuron-microglia crosstalk, mediated by the purinergic P2X7 receptor (R)/fractalkine/CX3CR1 cascade in the spinal cord dorsal horn, plays a pivotal role in pain processing. However, its involvement in the analgesic effect of electroacupuncture (EA) remains unclear. In this study, a rat neck-incision pain model was established by making a longitudinal incision along the midline of the neck and subsequent repeated mechanical stimulation. EA stimulation was applied to bilateral LI18, LI4-PC6, or ST36-GB34. The thermal pain threshold, cervicospinal ATP concentration, expression levels of purinergic P2XR and P2YR subunits mRNAs, and fractalkine, CX3CR1 and p38 MAPK proteins, were detected separately. The neck incision induced strong thermal hyperalgesia and upregulation of spinal ATP within 48 h. No significant change was found in thermal hyperalgesia after a single session of EA intervention. However, a single session of EA dramatically enhanced the neck incision-induced upregulation of ATP and upregulated the expression of P2X7R, which was reversed by two sessions of EA. Two sessions of EA at bilateral LI18 or LI4-PC6 attenuated hyperalgesia significantly, accompanied with downregulation of P2X7R/fractalkine/ CX3CR1 signaling after three sessions of EA. EA stimulation of LI18 or LI4-PC6 alleviates thermal hyperalgesia in neck-incision pain rats, which may be associated with its effects in regulating the neck incision-induced increase of ATP and P2X7R and subsequently suppressing fractalkine/CX3CR1 signaling in the cervical spinal cord.

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Section: Discussionsupporting

confidence: 76%

Effect of electroacupuncture on the cervicospinal P2X7 receptor/fractalkine/CX3CR1 signaling pathway in a rat neck-incision pain model

Gao

Wang

et al. 2016

Purinergic Signalling

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“…22,26,27 Findings from this cumulative effect suggest 4-5 sessions of acupuncture are optimal when presented a time-dependent manner. 22 As yet, no clinical studies have explored the accumulative effects of acupuncture in adults. To address this gap, we aim to conduct a RCT to evaluate the outcomes from 4, 7 and 10 sessions of acupuncture applied in addition to usual care in the treatment of chronic LBP in adults.…”

Section: Introductionmentioning

confidence: 88%

“…22 According to previous studies, a minimum of six sessions of acupuncture is optimal for chronic LBP, 23,24 and six to ten treatment sessions is the number generally reported by textbooks and clinical studies as well as in clinical practice. 25 The paucity of high-quality evidence to support the cumulative effects of repeated acupuncture interventions together with the effect of each treatment suggests the outcomes need further investigation.…”

Section: Introductionmentioning

confidence: 96%

Does the dose of Traditional Chinese Medicine acupuncture in addition to usual care affect outcomes for adults with chronic low back pain? Protocol for a randomized controlled feasibility study

Liu

Skinner

McDonough

et al. 2015

Physical Therapy Reviews

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Background: Acupuncture is considered a clinically effective and cost-effective treatment option for chronic low back pain. However, few clinical trials have evaluated the dose dependence of acupuncture for chronic low back pain based on the number of sessions. Conclusions are conflicting and there is little high-quality evidence to support the cumulative effects of repeated interventions. A randomized controlled trial to investigate the optimal number of sessions of acupuncture in addition to usual care for adults with chronic low back pain is required; a feasibility study to test the rationale and method for the full-scale trial is the first step in that process. Design: A pragmatic parallel three-armed randomized, controlled feasibility study. Methods: Forty-five participants with chronic low back pain will be recruited locally and randomized on a 1:1:1 basis to receive usual care plus 4 (n = 15), 7 (n = 15) or 10 sessions (n = 15) of semi-standardized acupuncture. Primary outcomes are acceptability of and adherence to different numbers of sessions of acupuncture, as well as the feasibility of the recruitment approach and completion of the specific outcome measures. Secondary outcomes include pain intensity and patient satisfaction. Follow-up questionnaires will be collected at discharge, 6, and 12 weeks after randomization. Discussion: Outcomes will inform the decision to conduct a full-scale trial to definitively test the dose dependence of acupuncture. Findings will add to the limited evidence available regarding the optimal number of sessions of acupuncture in the management of chronic low back pain, as well as being clinically relevant to clinicians, researchers and policy makers.

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“…Our previous study showed that the cumulative analgesic effect of repeated electroacupuncture (EA) intervention in neuropathic pain rats is closely associated with its regulatory effects on natural killer cells as well as some splenic and plasma cytokines [10]. Some findings suggested that multiple sessions of EA induced up-regulation of angiotensin I and II and the δ -opioid receptor in cerebral ischemia rats [11, 12].…”

Section: Introductionmentioning

confidence: 99%

Activation of hippocampal MEK1 contributes to the cumulative antinociceptive effect of electroacupuncture in neuropathic pain rats

Gao

Wang

et al. 2016

BMC Complement Altern Med

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BackgroundElectroacupuncture (EA) intervention can relieve a variety of pain; however, optimal EA protocols have not been clearly determined. In addition, although central mitogen-activated protein kinase kinase (MEK) signaling has been shown to be involved in the antinociceptive effect of acupuncture stimulation, its characteristics at different time-points of EA intervention have not been fully elucidated. Therefore, the present study investigated the relationship between the effects of different numbers of EA intervention sessions and the activation of MEK1 in the hippocampus and hypothalamus in a rat model of neuropathic pain.MethodsAfter ligation of the left sciatic nerve, which induces chronic constriction injury (CCI), the acupoints Zusanli (ST36) and Yanglingquan (GB34) were applied. The thermal withdrawal latency of the hind paw was used to evaluate the effect of EA on pain thresholds. Intra-hippocampus microinjection of PD98059, a MEK inhibitor, was performed to validate the involvement of MEK in EA analgesia. The hippocampus and hypothalamus were harvested to examine the phosphorylation levels of MEK (pMEK) by western blotting.ResultsIn CCI rats, the thermal pain threshold of the affected hind paw decreased significantly relative to the control. Following subsequent daily EA interventions, CCI-induced ipsilateral hyperalgesia was markedly improved from day 4 and the analgesic effect of EA lasted 3 days after cessation of EA. Four sessions of EA markedly suppressed CCI-induced decrease of hippocampal pMEK1 (normalized to the total MEK level). In contrast, successive sessions of EA intervention gradually down-regulated the CCI-induced up-regulation of hypothalamic pMEK1 along with the increase numbers of EA intervention. However, EA did not exert the same analgesic effect after microinjection of PD98059 into the contralateral hippocampus during the first 3 days of EA intervention.ConclusionsEA intervention can induce time-dependent cumulative analgesia in neuropathic pain rats after 4 successive sessions of daily EA intervention, which is at least in part related to the activation of hippocampal MEK1.

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NK cells mediate the cumulative analgesic effect of electroacupuncture in a rat model of neuropathic pain

Cited by 32 publications

References 38 publications

Effect of electroacupuncture on the cervicospinal P2X7 receptor/fractalkine/CX3CR1 signaling pathway in a rat neck-incision pain model

Effect of electroacupuncture on the cervicospinal P2X7 receptor/fractalkine/CX3CR1 signaling pathway in a rat neck-incision pain model

Does the dose of Traditional Chinese Medicine acupuncture in addition to usual care affect outcomes for adults with chronic low back pain? Protocol for a randomized controlled feasibility study

Activation of hippocampal MEK1 contributes to the cumulative antinociceptive effect of electroacupuncture in neuropathic pain rats

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