Electroacupuncture improves thermal and mechanical sensitivities in a rat model of postherpetic neuralgia

Molecular Pain

Man Li¹  Hui-lin Pan²  Jing Shi¹  Bo Tian¹  Xian-fang Meng¹  Fang Gao¹  Jia-qing Li¹  Yan Gao¹  Yin Zhao¹  Zheng-tao Lv¹  Cai-hua Wu¹ 

[1] Department of Neurobiology, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology, 13 Hangkong Road, Wuhan, 430030, P.R. China;Department of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX77030, USA

关键词: Axonal sprouting;    TRPV1;    Allodynia;    Analgesia;    Acupuncture;    Capsaicin;    Postherpetic neuralgia;    Neuropathic pain;   

Others  :  862531
DOI  :  10.1186/1744-8069-9-18

 received in 2013-02-07, accepted in 2013-03-14,  发布年份 2013

【 摘 要 】

Background

Electroacupuncture (EA) is effective in relieving pain in patients with postherpetic neuralgia (PHN). However, the mechanism underlying the therapeutic effect of EA in PHN is still unclear. Systemic injection of resiniferatoxin (RTX), an ultrapotent analog of TRPV1 agonist, in adult rats can reproduce the clinical symptoms of PHN by ablating TRPV1-expressing sensory neurons. In this study, we determined the beneficial effect of EA and the potential mechanisms in this rat model of PHN.

Methods

PHN was induced in rats by a single injection of RTX. Thermal hyperalgesia was tested with a radiant heat stimulus, and mechanical allodynia was quantified with von Frey filaments. TRPV1 receptors were shown by using immunofluorescence labeling. The ultrastructural changes of the sciatic nerve were assessed by electron microscopic examination. The sprouting of myelinated primary afferent terminals into the spinal dorsal horn was mapped by using the transganglionic tracer cholera toxin B-subunit (CTB).

Results

RTX injection diminished thermal sensitivity and gradually induced tactile allodynia within 3 weeks. EA applied to GB30 and GB34 at 2 and 15 Hz, but not 100 Hz, significantly increased the thermal sensitivity 4 weeks after treatment and decreased the tactile allodynia 2 weeks after treatment in RTX-treated rats. EA treatment at 2 and 15 Hz recovered the loss of TRPV1-positive dorsal root ganglion neurons and their central terminals of afferent fibers in the spinal superficial dorsal horn of RTX-treated rats. Moreover, EA significantly reduced the loss of unmyelinated fibers and the damage of the myelinated nerve fibers of RTX-treated rats. Furthermore, EA at 2 and 15 Hz inhibited the sprouting of myelinated primary afferent terminals into the spinal lamina II of RTX-treated rats.

Conclusions

EA treatment improves thermal perception by recovering TRPV1-positive sensory neurons and nerve terminals damaged by RTX. EA Also reduces RTX-induced tactile allodynia by attenuating the damage of myelinated afferent nerves and their abnormal sprouting into the spinal lamina II. Our study provides new information about the mechanisms of the therapeutic actions of EA in the treatment of PHN.

【 授权许可】

   
2013 Wu et al.; licensee BioMed Central Ltd.

【 图 表 】

【 参考文献 】

• [1]Baron R, Saguer M: Postherpetic neuralgia. Are C-nociceptors involved in signalling and maintenance of tactile allodynia? Brain 1993, 116(Pt 6):1477-1496.
• [2]Grachev Iu V, Kukushkin ML, Sudarikov AP, Zhuravlev VF, Gerasimenko M: Clinical course and treatment of herpetic trigeminal ganglionic neuropathy. Zh Nevrol Psikhiatr Im S S Korsakova 1998, 98:4-8.
• [3]Wang CY, Fang JQ: Analysis on therapeutic effect of variable-frequency electroacupuncture combined with herbal-moxa moxibustion for post-zoster neuralgia. Zhen Ci Yan Jiu 2012, 37:64-66.
• [4]Rowbotham MC, Fields HL: The relationship of pain, allodynia and thermal sensation in post-herpetic neuralgia. Brain 1996, 119(Pt 2):347-354.
• [5]Pan HL, Khan GM, Alloway KD, Chen SR: Resiniferatoxin induces paradoxical changes in thermal and mechanical sensitivities in rats: mechanism of action. J Neurosci 2003, 23:2911-2919.
• [6]Dalziel RG, Bingham S, Sutton D, Grant D, Champion JM, Dennis SA, Quinn JP, Bountra C, Mark MA: Allodynia in rats infected with varicella zoster virus–a small animal model for post-herpetic neuralgia. Brain Res Brain Res Rev 2004, 46:234-242.
• [7]Takasaki I, Andoh T, Shiraki K, Kuraishi Y: Allodynia and hyperalgesia induced by herpes simplex virus type-1 infection in mice. Pain 2000, 86:95-101.
• [8]Chen SR, Pan HL: Effect of systemic and intrathecal gabapentin on allodynia in a new rat model of postherpetic neuralgia. Brain Res 2005, 1042:108-113.
• [9]Tanaka N, Yamaga M, Tateyama S, Uno T, Tsuneyoshi I, Takasaki M: The effect of pulsed radiofrequency current on mechanical allodynia induced with resiniferatoxin in rats. Anesth Analg 2010, 111:784-790.
• [10]Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, Koltzenburg M, Basbaum AI, Julius D: Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 2000, 288:306-313.
• [11]Szallasi A, Blumberg PM: Vanilloid (Capsaicin) receptors and mechanisms. Pharmacol Rev 1999, 51:159-212.
• [12]Xu XJ, Farkas-Szallasi T, Lundberg JM, Hokfelt T, Wiesenfeld-Hallin Z, Szallasi A: Effects of the capsaicin analogue resiniferatoxin on spinal nociceptive mechanisms in the rat: behavioral, electrophysiological and in situ hybridization studies. Brain Res 1997, 752:52-60.
• [13]Aloe L, Manni L: Low-frequency electro-acupuncture reduces the nociceptive response and the pain mediator enhancement induced by nerve growth factor. Neurosci Lett 2009, 449:173-177.
• [14]Manni L, Florenzano F, Aloe L: Electroacupuncture counteracts the development of thermal hyperalgesia and the alteration of nerve growth factor and sensory neuromodulators induced by streptozotocin in adult rats. Diabetologia 2011, 54:1900-1908.
• [15]Zhang Z, Wang C, Gu G, Li H, Zhao H, Wang K, Han F, Wang G: The effects of electroacupuncture at the ST36 (Zusanli) acupoint on cancer pain and transient receptor potential vanilloid subfamily 1 expression in Walker 256 tumor-bearing rats. Anesth Analg 2012, 114:879-885.
• [16]Wang XY, Li XL, Hong SQ, Xi-Yang YB, Wang TH: Electroacupuncture induced spinal plasticity is linked to multiple gene expressions in dorsal root deafferented rats. J Mol Neurosci 2009, 37:97-110.
• [17]Zhou HL, Zhang LS, Kang Y, Zhang W, Wang TH: Effects of electro-acupuncture on CNTF expression in spared dorsal root ganglion and the associated spinal lamina II and nucleus dorsalis following adjacent dorsal root ganglionectomies in cats. Neuropeptides 2008, 42:95-106.
• [18]Li QW, Yisidatoulawo , Guo Y, Masidabenhaqi , Ma DM, Li GL, Wang F, Wang GJ: Effects of electroacupuncture at different frequencies on morphological changes of nervous tissues and electromyogram of skeletal muscles in the rat with injury of sciatic nerve. Zhongguo Zhen Jiu 2005, 25:217-220.
• [19]Hwang BG, Min BI, Kim JH, Na HS, Park DS: Effects of electroacupuncture on the mechanical allodynia in the rat model of neuropathic pain. Neurosci Lett 2002, 320:49-52.
• [20]Xing GG, Liu FY, Qu XX, Han JS, Wan Y: Long-term synaptic plasticity in the spinal dorsal horn and its modulation by electroacupuncture in rats with neuropathic pain. Exp Neurol 2007, 208:323-332.
• [21]Ma QP: Expression of capsaicin receptor (VR1) by myelinated primary afferent neurons in rats. Neurosci Lett 2002, 319:87-90.
• [22]Gracely RH, Lynch SA, Bennett GJ: Painful neuropathy: altered central processing maintained dynamically by peripheral input. Pain 1992, 51:175-194.
• [23]Koltzenburg M, Torebjork HE, Wahren LK: Nociceptor modulated central sensitization causes mechanical hyperalgesia in acute chemogenic and chronic neuropathic pain. Brain 1994, 117(Pt 3):579-591.
• [24]Nakamura S, Myers RR: Myelinated afferents sprout into lamina II of L3-5 dorsal horn following chronic constriction nerve injury in rats. Brain Res 1999, 818:285-290.
• [25]Nesic O, Sundberg LM, Herrera JJ, Mokkapati VU, Lee J, Narayana PA: Vascular endothelial growth factor and spinal cord injury pain. J Neurotrauma 2010, 27:1793-1803.
• [26]Woolf CJ, Shortland P, Coggeshall RE: Peripheral nerve injury triggers central sprouting of myelinated afferents. Nature 1992, 355:75-78.
• [27]Woolf CJ, Shortland P, Reynolds M, Ridings J, Doubell T, Coggeshall RE: Reorganization of central terminals of myelinated primary afferents in the rat dorsal horn following peripheral axotomy. J Comp Neurol 1995, 360:121-134.
• [28]Andrew D, Greenspan JD: Mechanical and heat sensitization of cutaneous nociceptors after peripheral inflammation in the rat. J Neurophysiol 1999, 82:2649-2656.
• [29]Zimmermann M: Ethical guidelines for investigations of experimental pain in conscious animals. Pain 1983, 16:109-110.
• [30]Khan GM, Chen SR, Pan HL: Role of primary afferent nerves in allodynia caused by diabetic neuropathy in rats. Neuroscience 2002, 114:291-299.
• [31]Chen L, Zhang J, Li F, Qiu Y, Wang L, Li YH, Shi J, Pan HL, Li M: Endogenous anandamide and cannabinoid receptor-2 contribute to electroacupuncture analgesia in rats. J Pain 2009, 10:732-739.
• [32]Zhang RX, Lao L, Wang L, Liu B, Wang X, Ren K, Berman BM: Involvement of opioid receptors in electroacupuncture-produced anti-hyperalgesia in rats with peripheral inflammation. Brain Res 2004, 1020:12-17.
• [33]Wang L, Zhang Y, Dai J, Yang J, Gang S: Electroacupuncture (EA) modulates the expression of NMDA receptors in primary sensory neurons in relation to hyperalgesia in rats. Brain Res 2006, 1120:46-53.
• [34]Hargreaves K, Dubner R, Brown F, Flores C, Joris J: A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 1988, 32:77-88.
• [35]Woodbury CJ, Ritter AM, Koerber HR: On the problem of lamination in the superficial dorsal horn of mammals: a reappraisal of the substantia gelatinosa in postnatal life. J Comp Neurol 2000, 417:88-102.