Alleviation of trigeminal neuropathic pain by electroacupuncture: the role of hyperpolarization-activated cyclic nucleotide-gated channel protein expression in the Gasserian ganglion

Abstract

Introduction:

The aim of this study was to examine the effect of electroacupuncture (EA) on trigeminal neuropathic pain in rats and explore the potential mechanism underlying the putative therapeutic effect of EA.

Methods:

Trigeminal neuropathic pain behavior was induced in rats by unilateral chronic constriction injury of the distal infraorbital nerve (dIoN-CCI). EA was administered at ST2 (Sibai) and Jiachengjiang. A total of 60 Sprague Dawley rats were divided into the following four groups (n = 15 per group) to examine the behavioral outcomes after surgery and/or EA treatment: sham (no ligation); dIoN-CCI (received isoflurane only, without EA treatment); dIoN-CCI+EA-7d (received EA treatment for 7 days); and dIoN-CCI+EA-14d (received EA treatment for 14 days). Both evoked and spontaneous nociceptive behaviors were measured. Of these, 12 rats (n = 4 from sham, dIoN-CCI, and dIoN-CCI+EA-14d groups, respectively) were used to analyze protein expression of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel in the Gasserian ganglion (GG) by immunohistochemistry.

Results:

dIoN-CCI rats exhibited mechanical allodynia and increased face-grooming activity that lasted at least 35 days. EA treatment reduced mechanical allodynia and face-grooming in dIoN-CCI rats. Overall, 14 days of EA treatment produced a prolonged anti-nociceptive effect as compared to 7-day EA treatment. The counts of HCN1 and HCN2 immunopositive puncta were increased in the ipsilateral GG in dIoN-CCI rats and were reduced by 14 days of EA treatment.

Discussion:

EA treatment relieved trigeminal neuropathic pain in dIoN-CCI rats, and this effect was dependent on the duration of EA treatment. The downregulation of HCN expression may contribute to the anti-nociceptive effect of EA in this rat model of trigeminal neuropathic pain.

Keywords

electroacupuncture Gasserian ganglion hyperpolarization-activated cyclic nucleotide-gated channel trigeminal neuropathic pain unilateral chronic constriction injury of the distal infraorbital nerve

Get full access to this article

View all access options for this article.

References

Woda

Tubert-Jeannin

Bouhassira

, et al. Towards a new taxonomy of idiopathic orofacial pain. Pain 2005; 116(3): 396–406.

Hitchon

Holland

Noeller

, et al. Options in treating trigeminal neuralgia: experience with 195 patients. Clin Neurol Neurosurg 2016; 149: 166–170.

Adams

Pendleton

Latimer

, et al. Harvey Cushing’s case series of trigeminal neuralgia at the Johns Hopkins Hospital: a surgeon’s quest to advance the treatment of the “suicide disease.” Acta Neurochir (Wien) 2011; 153(5): 1043–1050.

Montano

Conforti

Di Bonaventura

, et al. Advances in diagnosis and treatment of trigeminal neuralgia. Ther Clin Risk Manag 2015; 11: 289–299.

Sweet

WH.

The treatment of trigeminal neuralgia (tic douloureux). N Engl J Med 1986; 315(3): 174–177.

Koopman

de Vries

Dieleman

, et al. A nationwide study of three invasive treatments for trigeminal neuralgia. Pain 2011; 152(3): 507–513.

Chen

, et al. The efficacy of acupuncture in post-operative pain management: a systematic review and meta-analysis. PLoS ONE 2016; 11(3): e0150367.

Yang

Zhao

Xie

, et al. The effectiveness of acupuncture for chronic pain with depression: a systematic review protocol. Medicine (Baltimore) 2017; 96(47): e8800.

Abuaisha

Costanzi

Boulton

AJ.

Acupuncture for the treatment of chronic painful peripheral diabetic neuropathy: a long-term study. Diabetes Res Clin Pract 1998; 39(2): 115–121.

10.

Huang

Huo

Zhao

Efficacy on primary trigeminal neuralgia treated with triple puncture technique and electroacupuncture at trigger points. Zhongguo Zhen Jiu 2017; 37(1): 31–34.

11.

Costantini

Tomasello

Buonopane

, et al. Treatment of trigeminal neuralgia with electroacupuncture. Experience with 104 cases. Ann Ital Chir 1995; 66(3): 373–378.

12.

Hsu

Hsieh

, et al. Probing the effects and mechanisms of electroacupuncture at ipsilateral or contralateral ST36-ST37 acupoints on CFA-induced inflammatory pain. Sci Rep 2016; 6: 22123.

13.

Zhang

Sun

Xin

, et al. Contralateral electroacupuncture relieves chronic neuropathic pain in rats with spared nerve injury. Med Sci Monit 2018; 24: 2970–2974.

14.

Chen

Liu

, et al. Cognitive effects of electro-acupuncture and pregabalin in a trigeminal neuralgia rat model induced by cobra venom. J Pain Res 2017; 10: 1887–1897.

15.

Zhang

Lao

Ren

, et al. Mechanisms of acupuncture-electroacupuncture on persistent pain. Anesthesiology 2014; 120(2): 482–503.

16.

Gao

McMullan

Djouhri

, et al. Expression and properties of hyperpolarization-activated current in rat dorsal root ganglion neurons with known sensory function. J Physiol 2012; 590(19): 4691–4705.

17.

Momin

Cadiou

Mason

, et al. Role of the hyperpolarization-activated current Ih in somatosensory neurons. J Physiol 2008; 586(24): 5911–5929.

18.

Cho

Furness

Jennings

EA.

Postnatal maturation of the hyperpolarization-activated cation current, I(h), in trigeminal sensory neurons. J Neurophysiol 2011; 106(4): 2045–2056.

19.

Cho

Staikopoulos

Ivanusic

, et al. Hyperpolarization-activated cyclic-nucleotide gated 4 (HCN4) protein is expressed in a subset of rat dorsal root and trigeminal ganglion neurons. Cell Tissue Res 2009; 338(2): 171–177.

20.

Chaplan

Guo

Lee

, et al. Neuronal hyperpolarization-activated pacemaker channels drive neuropathic pain. J Neurosci 2003; 23(4): 1169–1178.

21.

Wan

Involvement of hyperpolarization-activated, cyclic nucleotide-gated cation channels in dorsal root ganglion in neuropathic pain. Sheng Li Xue Bao 2008; 60(5): 579–580.

22.

Weng

Smith

Sathish

, et al. Chronic inflammatory pain is associated with increased excitability and hyperpolarization-activated current (Ih) in C- but not Adelta-nociceptors. Pain 2012; 153(4): 900–914.

23.

Acosta

McMullan

Djouhri

, et al. HCN1 and HCN2 in Rat DRG neurons: levels in nociceptors and non-nociceptors, NT3-dependence and influence of CFA-induced skin inflammation on HCN2 and NT3 expression. PLoS ONE 2012; 7(12): e50442.

24.

Liao

Liu

, et al. Is ZD7288 a selective blocker of hyperpolarization-activated cyclic nucleotide-gated channel currents? Channels (Austin) 2012; 6(6): 438–442.

25.

Noh

Kumar

Bukhanova

, et al. The heart-rate-reducing agent, ivabradine, reduces mechanical allodynia in a rodent model of neuropathic pain. Eur J Pain 2014; 18(8): 1139–1147.

26.

Takasu

Ono

Tanabe

Spinal hyperpolarization-activated cyclic nucleotide-gated cation channels at primary afferent terminals contribute to chronic pain. Pain 2010; 151(1): 87–96.

27.

Ding

You

Shen

, et al. Increased HCN channel activity in the Gasserian ganglion contributes to trigeminal neuropathic pain. J Pain 2018; 19(6): 626–634.

28.

Ding

You

Shen

, et al. An improved rodent model of trigeminal neuropathic pain by unilateral chronic constriction injury of distal infraorbital nerve. J Pain 2017; 18(8): 899–907.

29.

YS.

Target points: a discussion on acupuncture treatment of primary trigeminal neuralgia. Zhong Xi Yi Jie He Xue Bao 2012; 10(9): 961–965.

30.

Spezia Adachi

Vercelino

de Oliveira

, et al. Isoflurane and the analgesic effect of acupuncture and electroacupuncture in an animal model of neuropathic pain. J Acupunct Meridian Stud 2018; 11(3): 97–106.

31.

Kouranova

Strassle

Ring

, et al. Hyperpolarization-activated cyclic nucleotide-gated channel mRNA and protein expression in large versus small diameter dorsal root ganglion neurons: correlation with hyperpolarization-activated current gating. Neuroscience 2008; 153(4): 1008–1019.

32.

Moosmang

Stieber

Zong

, et al. Cellular expression and functional characterization of four hyperpolarization-activated pacemaker channels in cardiac and neuronal tissues. Eur J Biochem 2001; 268(6): 1646–1652.

33.

Schnorr

Eberhardt

Kistner

, et al. HCN2 channels account for mechanical (but not heat) hyperalgesia during long-standing inflammation. Pain 2014; 155(6): 1079–1090.

34.

Djouhri

Al Otaibi

Kahlat

, et al. Persistent hindlimb inflammation induces changes in activation properties of hyperpolarization-activated current (Ih) in rat C-fiber nociceptors in vivo. Neuroscience 2015; 301: 121–133.

35.

Cho

Kim

Moozhayil

, et al. The expression of hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1) and HCN2 in the rat trigeminal ganglion, sensory root, and dental pulp. Neuroscience 2015; 291: 15–25.

36.

Fox

Loftus

Tamkun

MM.

Regulation of Kv2.1 K(+) conductance by cell surface channel density. J Neurosci 2013; 33(3): 1259–1270.