Open Access

Effect of electro-acupuncture on the BDNF-TrkB pathway in the spinal cord of CCI rats

  • Authors:
    • Wen-Zhan Tu
    • Si-Si Li
    • Xia Jiang
    • Xin-Ru Qian
    • Guan-Hu Yang
    • Peng-Peng Gu
    • Bin Lu
    • Song-He Jiang
  • View Affiliations

  • Published online on: March 13, 2018     https://doi.org/10.3892/ijmm.2018.3563
  • Pages: 3307-3315
  • Copyright: © Tu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Microglia, which comprise a sensor for pathological events in the central nervous system, may be triggered by nerve injury and transformed from a quiescent state into an activated state; ionised calcium binding adaptor molecule 1 (Iba1) is a sensitive marker associated with activated microglia. Accumulated evidence suggests that spinal activated microglia and the brain-derived neurotrophic factor (BDNF)-tyrosine kinase receptor B (TrkB) signalling pathway play major roles in the production and development of neuropathic pain. Electro-acupuncture (EA) has a positive effect on relieving chronic neuropathic pain; however, the underlying mechanisms remain unclear. To determine the significance of EA in the treatment of neuropathic pain mediated by activated microglia and the BDNF-TrkB signalling pathway in the spinal cord, the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) values were recorded to assess hyperalgesia and allodynia. In addition, the amount of activated microglia and BDNF were assessed via immunofluorescence. Iba1, BDNF and TrkB mRNA expression levels were examined using qPCR; the protein levels of BDNF, p-TrkB and TrkB in the spinal cord were analysed via western blotting. The present study demonstrated that EA treatment increased the MWT and TWL values. EA significantly inhibited the proportion of activated microglia and BDNF expression in the spinal cord after chronic constrictive injury (CCI). Furthermore, EA decreased the expression of BDNF and TrkB at both the mRNA and protein levels in the spinal cord of CCI rats. These findings suggest that the analgesic effect of EA may be achieved by inhibiting the activation of spinal microglia and subsequently blocking the BDNF-TrkB signalling pathway.

References

1 

Baron R: Neuropathic pain: A clinical perspective. Handb Exp Pharmacol. 194:3–30. 2009. View Article : Google Scholar

2 

Goettl VM, Huang Y, Hackshaw KV and Stephens RL Jr: Reduced basal release of serotonin from the ventrobasal thalamus of the rat in a model of neuropathic pain. Pain. 99:359–366. 2002. View Article : Google Scholar : PubMed/NCBI

3 

Smith HS: Opioids and neuropathic pain. Pain Physician. 15(Suppl 3): ES93–ES110. 2012.PubMed/NCBI

4 

Ren W, Tu W, Jiang S, Cheng R and Du Y: Electroacupuncture improves neuropathic pain: Adenosine, adenosine 5′-triphosphate disodium and their receptors perhaps change simultaneously. Neural Regen Res. 7:2618–2623. 2012.PubMed/NCBI

5 

Tu W, Wang W, Xi H, He R, Gao L and Jiang S: Regulation of neurotrophin-3 and interleukin-1beta and inhibition of spinal glial activation contribute to the analgesic effect of electroacu-puncture in chronic neuropathic pain states of rats. Evid Based Complement Alternat Med. 2015:6420812015. View Article : Google Scholar

6 

Tsuda M, Beggs S, Salter MW and Inoue K: Microglia and intractable chronic pain. Glia. 61:55–61. 2013. View Article : Google Scholar

7 

Zhang X, Xu Y, Wang J, Zhou Q, Pu S, Jiang W and Du D: The effect of intrathecal administration of glial activation inhibitors on dorsal horn BDNF overexpression and hind paw mechanical allodynia in spinal nerve ligated rats. J Neural Transm Vienna. 119:329–336. 2012. View Article : Google Scholar

8 

Pandya CD, Kutiyanawalla A and Pillai A: BDNF-TrkB signaling and neuroprotection in schizophrenia. Asian J Psychiatr. 6:22–28. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Xing GG, Liu FY, Qu XX, Han JS and Wan Y: Long-term synaptic plasticity in the spinal dorsal horn and its modulation by electroacupuncture in rats with neuropathic pain. Exp Neurol. 208:323–332. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Kim SK, Park JH, Bae SJ, Kim JH, Hwang BG, Min BI, Park DS and Na HS: Effects of electroacupuncture on cold allodynia in a rat model of neuropathic pain: Mediation by spinal adrenergic and serotonergic receptors. Exp Neurol. 195:430–436. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Lau WK, Lau YM, Zhang HQ, Wong SC and Bian ZX: Electroacupuncture versus celecoxib for neuropathic pain in rat SNL model. Neuroscience. 170:655–661. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Sun S, Cao H, Han M, Li TT, Zhao ZQ and Zhang YQ: Evidence for suppression of electroacupuncture on spinal glial activation and behavioral hypersensitivity in a rat model of monoarthritis. Brain Res Bull. 75:83–93. 2008. View Article : Google Scholar

13 

Fox A, Kesingland A, Gentry C, McNair K, Patel S, Urban L and James I: The role of central and peripheral Cannabinoid1 receptors in the antihyperalgesic activity of cannabinoids in a model of neuropathic pain. Pain. 92:91–100. 2001. View Article : Google Scholar : PubMed/NCBI

14 

Huang C, Li HT, Shi YS, Han JS and Wan Y: Ketamine potentiates the effect of electroacupuncture on mechanical allodynia in a rat model of neuropathic pain. Neurosci Lett. 368:327–331. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Gao YH, Wang JY, Qiao LN, Chen SP, Tan LH, Xu QL and Liu JL: NK cells mediate the cumulative analgesic effect of electroacupuncture in a rat model of neuropathic pain. BMC Complement Altern Med. 14:3162014. View Article : Google Scholar : PubMed/NCBI

16 

Tu WZ, Cheng RD, Cheng B, Lu J, Cao F, Lin HY, Jiang YX, Wang JZ, Chen H and Jiang SH: Analgesic effect of electroacupuncture on chronic neuropathic pain mediated by P2X3 receptors in rat dorsal root ganglion neurons. Neurochem Int. 60:379–386. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Wang WS, Tu WZ, Cheng RD, He R, Ruan LH, Zhang L, Gong YS, Fan XF, Hu J, Cheng B, et al: Electroacupuncture and A-317491 depress the transmission of pain on primary afferent mediated by the P2X3 receptor in rats with chronic neuropathic pain states. J Neurosci Res. 92:1703–1713. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Silva JR, Silva ML and Prado WA: Analgesia induced by 2- or 100-Hz electroacupuncture in the rat tail-flick test depends on the activation of different descending pain inhibitory mechanisms. J Pain. 12:51–60. 2011. View Article : Google Scholar

19 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar

20 

Filshie J: The non-drug treatment of neuralgic and neuropathic pain of malignancy. Cancer Surv. 7:161–193. 1988.PubMed/NCBI

21 

Wong JY and Rapson LM: Acupuncture in the management of pain of musculoskeletal and neurologic origin. Phys Med Rehabil Clin N Am. 10:531–545. vii–viii. 1999.PubMed/NCBI

22 

Qin Z, Liu X, Yao Q, Zhai Y and Liu Z: Acupuncture for treating sciatica: A systematic review protocol. BMJ Open. 5:e0074982015. View Article : Google Scholar : PubMed/NCBI

23 

Zhao ZQ: Neural mechanism underlying acupuncture analgesia. Prog Neurobiol. 85:355–375. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Chen S, Wang S, Rong P, Wang J, Qiao L, Feng X, Liu J and Zhang J: Acupuncture for visceral pain: neural substrates and potential mechanisms. Evid Based Complement Alternat Med. 2014:6095942014. View Article : Google Scholar

25 

Trang T, Beggs S and Salter MW: Brain-derived neurotrophic factor from microglia: A molecular substrate for neuropathic pain. Neuron Glia Biol. 7:99–108. 2011. View Article : Google Scholar

26 

Mika J, Zychowska M, Popiolek-Barczyk K, Rojewska E and Przewlocka B: Importance of glial activation in neuropathic pain. Eur J Pharmacol. 716:106–119. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Inoue K, Tsuda M and Tozaki-Saitoh H: Role of the glia in neuropathic pain caused by peripheral nerve injury. Brain Nerve. 64:1233–1239. 2012.In Japanese. PubMed/NCBI

28 

Liang LL, Yang JL, Lü N, Gu XY, Zhang YQ and Zhao ZQ: Synergetic analgesia of propentofylline and electroacupuncture by interrupting spinal glial function in rats. Neurochem Res. 35:1780–1786. 2010. View Article : Google Scholar : PubMed/NCBI

29 

Choi DC, Lee JY, Lim EJ, Baik HH, Oh TH and Yune TY: Inhibition of ROS-induced P38MAPK and ERK activation in microglia by acupuncture relieves neuropathic pain after spinal cord injury in rats. Exp Neurol. 236:268–282. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Shan S, Qi-Liang MY, Hong C, Tingting L, Mei H, Haili P, Yan-Qing W, Zhi-Qi Z and Yu-Qiu Z: Is functional state of spinal microglia involved in the anti-allodynic and anti-hyperalgesic effects of electroacupuncture in rat model of monoarthritis? Neurobiol Dis. 26:558–568. 2007. View Article : Google Scholar : PubMed/NCBI

31 

Narita M, Yoshida T, Nakajima M, Narita M, Miyatake M, Takagi T, Yajima Y and Suzuki T: Direct evidence for spinal cord microglia in the development of a neuropathic pain-like state in mice. J Neurochem. 97:1337–1348. 2006. View Article : Google Scholar : PubMed/NCBI

32 

Coull JA, Beggs S, Boudreau D, Boivin D, Tsuda M, Inoue K, Gravel C, Salter MW and De Koninck Y: BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature. 438:1017–1021. 2005. View Article : Google Scholar : PubMed/NCBI

33 

Zhang W, Liu LY and Xu TL: Reduced potassium-chloride co-transporter expression in spinal cord dorsal horn neurons contributes to inflammatory pain hypersensitivity in rats. Neuroscience. 152:502–510. 2008. View Article : Google Scholar : PubMed/NCBI

34 

Rivera C, Voipio J, Thomas-Crusells J, Li H, Emri Z, Sipilä S, Payne JA, Minichiello L, Saarma M and Kaila K: Mechanism of activity-dependent downregulation of the neuron-specific K-Cl cotransporter KCC2. J Neurosci. 24:4683–4691. 2004. View Article : Google Scholar : PubMed/NCBI

35 

Coull JA, Boudreau D, Bachand K, Prescott SA, Nault F, Sík A, De Koninck P and De Koninck Y: Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain. Nature. 424:938–942. 2003. View Article : Google Scholar : PubMed/NCBI

36 

Biggs JE, Lu VB, Stebbing MJ, Balasubramanyan S and Smith PA: Is BDNF sufficient for information transfer between microglia and dorsal horn neurons during the onset of central sensitization? Mol Pain. 6:442010. View Article : Google Scholar : PubMed/NCBI

37 

Kahle KT, Staley KJ, Nahed BV, Gamba G, Hebert SC, Lifton RP and Mount DB: Roles of the cation-chloride cotransporters in neurological disease. Nat Clin Pract Neurol. 4:490–503. 2008. View Article : Google Scholar : PubMed/NCBI

38 

Cordero-Erausquin M, Coull JA, Boudreau D, Rolland M and De Koninck Y: Differential maturation of GABA action and anion reversal potential in spinal lamina I neurons: Impact of chloride extrusion capacity. J Neurosci. 25:9613–9623. 2005. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
APA
Tu, W., Li, S., Jiang, X., Qian, X., Yang, G., Gu, P. ... Jiang, S. (2018). Effect of electro-acupuncture on the BDNF-TrkB pathway in the spinal cord of CCI rats. International Journal of Molecular Medicine, 41, 3307-3315. https://doi.org/10.3892/ijmm.2018.3563
MLA
Tu, W., Li, S., Jiang, X., Qian, X., Yang, G., Gu, P., Lu, B., Jiang, S."Effect of electro-acupuncture on the BDNF-TrkB pathway in the spinal cord of CCI rats". International Journal of Molecular Medicine 41.6 (2018): 3307-3315.
Chicago
Tu, W., Li, S., Jiang, X., Qian, X., Yang, G., Gu, P., Lu, B., Jiang, S."Effect of electro-acupuncture on the BDNF-TrkB pathway in the spinal cord of CCI rats". International Journal of Molecular Medicine 41, no. 6 (2018): 3307-3315. https://doi.org/10.3892/ijmm.2018.3563