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Ascending Nociceptive Control Contributes to the Antinociceptive Effect of Acupuncture in a Rat Model of Acute Pain

Published:January 13, 2014DOI:https://doi.org/10.1016/j.jpain.2013.12.008

      Abstract

      Acupuncture-induced analgesia depends on the activation of endogenous pain modulation pathways. In this study, we asked whether ascending nociceptive control (ANC), a form of pain-induced analgesia, contributes to the antinociceptive effect of acupuncture. To answer this question, we tested the ability of procedures that block ANC-induced analgesia, at peripheral, spinal, nucleus accumbens and rostral ventral medulla levels, to block acupuncture-induced analgesia. Acupuncture at ST36 (Zusanli), a widely used acupoint located in the hind limb, induced potent heterosegmental antinociception in the orofacial formalin test. The magnitude of this antinociceptive effect was similar to that induced by an intraplantar injection of capsaicin, a procedure classically used to activate ANC. The antinociceptive effect of acupuncture was blocked by sciatic C-fibers depletion (1% perineural capsaicin), spinal administration of a μ-opioid (Cys2,Tyr3,Orn5,Pen7amide, .2 μg) or of a GABAA (bicuculline, .3 μg) receptor antagonist, intra–nucleus accumbens administration of a μ-opioid receptor antagonist (Cys2,Tyr3,Orn5,Pen7amide, 1 μg), or intrarostral ventral medulla administration of a nicotinic acetylcholine receptor antagonist (mecamylamine, .6 μg). In addition, acupuncture at ST36 and/or upper lip formalin induced c-Fos expression in the nucleus accumbens and in rostral ventral medulla. On the basis of these results, we propose that ANC contributes to the antinociceptive effect of acupuncture.

      Perspective

      This article presents a novel mechanism of acupuncture analgesia, contributing to the understanding of its scientific basis. Because ANC is a pain modulation pathway activated by peripheral noxious stimulation that ascends to supraspinal regions, it could be the link between acupoint stimulation and the central mechanisms underlying acupuncture analgesia.

      Key words

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      References

        • Behbehani M.M.
        The role of acetylcholine in the function of the nucleus raphe magnus and in the interaction of this nucleus with the periaqueductal gray.
        Brain Res. 1982; 252: 299-307
        • Bing Z.
        • Villanueva L.
        • Le Bars D.
        Acupuncture and diffuse noxious inhibitory controls: Naloxone-reversible depression of activities of trigeminal convergent neurons.
        Neuroscience. 1990; 37: 809-818
        • Bouhassira D.
        • Chitour D.
        • Villaneuva L.
        • Le Bars D.
        The spinal transmission of nociceptive information: Modulation by the caudal medulla.
        Neuroscience. 1995; 69: 931-938
        • Brinkhaus B.
        • Witt C.M.
        • Jena S.
        • Linde K.
        • Streng A.
        • Wagenpfeil S.
        • Irnich D.
        • Walther H.U.
        • Melchart D.
        • Willich S.N.
        Acupuncture in patients with chronic low back pain: A randomized controlled trial.
        Arch Intern Med. 2006; 166: 450-457
        • Caterina M.J.
        • Schumacher M.A.
        • Tominaga M.
        • Rosen T.A.
        • Levine J.D.
        • Julius D.
        The capsaicin receptor: A heat-activated ion channel in the pain pathway.
        Nature. 1997; 389: 816-824
        • Chen-yu C.
        • Jen-yi L.
        • Teh-hsing C.
        • Yao-hui P.
        • Shu-chieh C.
        Studies on spinal ascending pathway for effect of acupuncture analgesia in rabbits.
        Sci Sin. 1975; 18: 651-658
        • Chen X.H.
        • Han J.S.
        Analgesia induced by electroacupuncture of different frequencies is mediated by different types of opioid receptors: Another cross-tolerance study.
        Behav Brain Res. 1992; 47: 143-149
        • Chen X.H.
        • Han J.S.
        All three types of opioid receptors in the spinal cord are important for 2/15 Hz electroacupuncture analgesia.
        Eur J Pharmacol. 1992; 211: 203-210
        • Cheng R.S.
        • Pomeranz B.
        Electroacupuncture analgesia could be mediated by at least two pain-relieving mechanisms; endorphin and non-endorphin systems.
        Life Sci. 1979; 25: 1957-1962
        • Cherkin D.C.
        • Sherman K.J.
        • Avins A.L.
        • Erro J.H.
        • Ichikawa L.
        • Barlow W.E.
        • Delaney K.
        • Hawkes R.
        • Hamilton L.
        • Pressman A.
        • Khalsa P.S.
        • Deyo R.A.
        A randomized trial comparing acupuncture, simulated acupuncture, and usual care for chronic low back pain.
        Arch Intern Med. 2009; 169: 858-866
        • Clement-Jones V.
        • McLoughlin L.
        • Tomlin S.
        • Besser G.M.
        • Rees L.H.
        • Wen H.L.
        Increased beta-endorphin but not met-enkephalin levels in human cerebrospinal fluid after acupuncture for recurrent pain.
        Lancet. 1980; 2: 946-949
        • Dai J.L.
        • Zhu Y.H.
        • Li X.Y.
        • Huang D.K.
        • Xu S.F.
        C-fos expression during electroacupuncture analgesia in rats—An immunohistochemical study.
        Acupunct Electrother Res. 1992; 17: 165-176
        • de Medeiros M.A.
        • Canteras N.S.
        • Suchecki D.
        • Mello L.E.
        Analgesia and c-Fos expression in the periaqueductal gray induced by electroacupuncture at the Zusanli point in rats.
        Brain Res. 2003; 973: 196-204
        • Ferrari L.F.
        • Gear R.W.
        • Levine J.D.
        Attenuation of activity in an endogenous analgesia circuit by ongoing pain in the rat.
        J Neurosci. 2010; 30: 13699-13706
        • Fields H.
        State-dependent opioid control of pain.
        Nat Rev Neurosci. 2004; 5: 565-575
        • Gear R.W.
        • Levine J.D.
        Antinociception produced by an ascending spino-supraspinal pathway.
        J Neurosci. 1995; 15: 3154-3161
        • Gear R.W.
        • Levine J.D.
        Rostral ventral medulla cholinergic mechanism in pain-induced analgesia.
        Neurosci Lett. 2009; 464: 170-172
        • Gear R.W.
        • Aley K.O.
        • Levine J.D.
        Pain-induced analgesia mediated by mesolimbic reward circuits.
        J Neurosci. 1999; 19: 7175-7181
        • Gilchrist H.D.
        • Allard B.L.
        • Simone D.A.
        Enhanced withdrawal responses to heat and mechanical stimuli following intraplantar injection of capsaicin in rats.
        Pain. 1996; 67: 179-188
        • Ha H.
        • Tan E.C.
        • Fukunaga H.
        • Aochi O.
        Naloxone reversal of acupuncture analgesia in the monkey.
        Exp Neurol. 1981; 73: 298-303
        • Han J.S.
        Acupuncture and endorphins.
        Neurosci Lett. 2004; 361: 258-261
        • Han J.S.
        Acupuncture analgesia: Areas of consensus and controversy.
        Pain. 2011; 152: S41-S48
        • Heinricher M.M.
        • Tavares I.
        • Leith J.L.
        • Lumb B.M.
        Descending control of nociception: Specificity, recruitment and plasticity.
        Brain Res Rev. 2009; 60: 214-225
        • Huang C.
        • Wang Y.
        • Chang J.K.
        • Han J.S.
        Endomorphin and mu-opioid receptors in mouse brain mediate the analgesic effect induced by 2 Hz but not 100 Hz electroacupuncture stimulation.
        Neurosci Lett. 2000; 294: 159-162
        • Ji R.R.
        • Zhang Z.W.
        • Zhou Y.
        • Zhang Q.
        • Han J.S.
        Induction of c-fos expression in the rostral medulla of rats following electroacupuncture stimulation.
        Int J Neurosci. 1993; 72: 183-191
        • Jin W.Q.
        • Zhou Z.F.
        • Han J.S.
        Inhibition of enkephalins degradation in the nucleus accumbens leads to potentiation of acupuncture and morphine analgesia.
        Sheng Li Xue Bao. 1985; 37: 377-382
        • Kagitani F.
        • Uchida S.
        • Hotta H.
        Afferent nerve fibers and acupuncture.
        Auton Neurosci. 2010; 157: 2-8
        • Le Bars D.
        • Dickenson A.H.
        • Besson J.M.
        Diffuse noxious inhibitory controls (DNIC), I; Effects on dorsal horn convergent neurones in the rat.
        Pain. 1979; 6: 283-304
        • Li C.
        • Zhu L.
        • Li W.
        • Ji C.
        Relationship between the presynaptic depolarization effect of acupuncture and γ-aminobutyric acid, opioid peptide and substance P.
        Zhen Ci Yan Jiu. 1993; 18: 178-182
        • Liu X.
        The role of negative feedback modulating pain of nucleus raphe magnus in electroacupuncture analgesia.
        Zhen Ci Yan Jiu. 1990; 15: 159-166
        • Liu X.
        The modulation of cerebral cortex and subcortical nuclei on NRM and their role in acupuncture analgesia.
        Zhen Ci Yan Jiu. 1996; 21: 4-11
        • Liu X.A.
        • Jiang M.C.
        • Huang P.B.
        • Zou T.
        Role of afferent C fibers in electroacupuncture of “zusanli” point in activating nucleus raphe magnus.
        Sheng Li Xue Bao. 1990; 42: 523-533
        • Lund I.
        • Lundeberg T.
        Are minimal, superficial or sham acupuncture procedures acceptable as inert placebo controls?.
        Acupunct Med. 2006; 24: 13-15
        • Lund I.
        • Naslund J.
        • Lundeberg T.
        Minimal acupuncture is not a valid placebo control in randomised controlled trials of acupuncture: A physiologist's perspective.
        Chin Med. 2009; 4: 1
        • Mayer D.J.
        • Price D.D.
        • Rafii A.
        Antagonism of acupuncture analgesia in man by the narcotic antagonist naloxone.
        Brain Res. 1977; 121: 368-372
        • Molsberger A.F.
        • Schneider T.
        • Gotthardt H.
        • Drabik A.
        German Randomized Acupuncture Trial for Chronic Shoulder Pain (GRASP)—A pragmatic, controlled, patient-blinded, multi-centre trial in an outpatient care environment.
        Pain. 2010; 151: 146-154
        • Oh S.H.
        • Imbe H.
        • Iwai-Liao Y.
        TMJ inflammation increases Fos expression in the nucleus raphe magnus induced by subsequent formalin injection of the masseter or hindpaw of rats.
        Okajimas Folia Anat Jpn. 2006; 83: 43-52
        • Ohtori S.
        • Takahashi K.
        • Chiba T.
        • Takahashi Y.
        • Yamagata M.
        • Sameda H.
        • Moriya H.
        Fos expression in the rat brain and spinal cord evoked by noxious stimulation to low back muscle and skin.
        Spine (Phila Pa 1976). 2000; 25: 2425-2430
        • Okada K.
        • Oshima M.
        • Kawakita K.
        Examination of the afferent fiber responsible for the suppression of jaw-opening reflex in heat, cold, and manual acupuncture stimulation in rats.
        Brain Res. 1996; 740: 201-207
        • Papir-Kricheli D.
        • Frey J.
        • Laufer R.
        • Gilon C.
        • Chorev M.
        • Selinger Z.
        • Devor M.
        Behavioural effects of receptor-specific substance P agonists.
        Pain. 1987; 31: 263-276
        • Paxinos G.
        • Watson C.
        The Rat Brain in Stereotaxic Coordinates.
        6th ed. Academic Press, New York2007
        • Raboisson P.
        • Dallel R.
        The orofacial formalin test.
        Neurosci Biobehav Rev. 2004; 28: 219-226
        • Romita V.V.
        • Yashpal K.
        • Hui-Chan C.W.
        • Henry J.L.
        Intense peripheral electrical stimulation evokes brief and persistent inhibition of the nociceptive tail withdrawal reflex in the rat.
        Brain Res. 1997; 761: 192-202
        • Sato T.
        • Takeshige C.
        • Shimizu S.
        Morphine analgesia mediated by activation of the acupuncture-analgesia-producing system.
        Acupunct Electrother Res. 1991; 16: 13-26
        • Schmidt B.L.
        • Tambeli C.H.
        • Levine J.D.
        • Gear R.W.
        Mu/delta cooperativity and opposing kappa-opioid effects in nucleus accumbens-mediated antinociception in the rat.
        Eur J Neurosci. 2002; 15: 861-868
        • Shen E.
        • Ma W.H.
        • Lan C.
        Involvement of descending inhibition in the effect of acupuncture on the splanchnically evoked potential in the orbital cortex of cat.
        Sci Sin. 1978; 21: 677-685
        • Sjolund B.
        • Terenius L.
        • Eriksson M.
        Increased cerebrospinal fluid levels of endorphins after electro-acupuncture.
        Acta Physiol Scand. 1977; 100: 382-384
        • Szigeti C.
        • Santha P.
        • Kortvely E.
        • Nyari T.
        • Horvath V.J.
        • Deak E.
        • Dux M.
        • Gulya K.
        • Jancso G.
        Disparate changes in the expression of transient receptor potential vanilloid type 1 receptor mRNA and protein in dorsal root ganglion neurons following local capsaicin treatment of the sciatic nerve in the rat.
        Neuroscience. 2012; 201: 320-330
        • Takeshige C.
        • Sato T.
        • Mera T.
        • Hisamitsu T.
        • Fang J.
        Descending pain inhibitory system involved in acupuncture analgesia.
        Brain Res Bull. 1992; 29: 617-634
        • Tambeli C.H.
        • Levine J.D.
        • Gear R.W.
        Centralization of noxious stimulus-induced analgesia (NSIA) is related to activity at inhibitory synapses in the spinal cord.
        Pain. 2009; 143: 228-232
        • Tambeli C.H.
        • Parada C.A.
        • Levine J.D.
        • Gear R.W.
        Inhibition of tonic spinal glutamatergic activity induces antinociception in the rat.
        Eur J Neurosci. 2002; 16: 1547-1553
        • Tambeli C.H.
        • Quang P.
        • Levine J.D.
        • Gear R.W.
        Contribution of spinal inhibitory receptors in heterosegmental antinociception induced by noxious stimulation.
        Eur J Neurosci. 2003; 18: 2999-3006
        • Tobbackx Y.
        • Meeus M.
        • Wauters L.
        • De Vilder P.
        • Roose J.
        • Verhaeghe T.
        • Nijs J.
        Does acupuncture activate endogenous analgesia in chronic whiplash-associated disorders? A randomized crossover trial.
        Eur J Pain. 2013; 17: 279-289
        • Vas J.
        • Perea-Milla E.
        • Mendez C.
        • Sanchez Navarro C.
        • Leon Rubio J.M.
        • Brioso M.
        • Garcia Obrero I.
        Efficacy and safety of acupuncture for chronic uncomplicated neck pain: A randomised controlled study.
        Pain. 2006; 126: 245-255
        • Vas J.
        • Aranda J.M.
        • Modesto M.
        • Benitez-Parejo N.
        • Herrera A.
        • Martinez-Barquin D.M.
        • Aguilar I.
        • Sanchez-Araujo M.
        • Rivas-Ruiz F.
        Acupuncture in patients with acute low back pain: A multicentre randomised controlled clinical trial.
        Pain. 2012; 153: 1883-1889
        • Vase L.
        • Baram S.
        • Takakura N.
        • Yajima H.
        • Takayama M.
        • Kaptchuk T.J.
        • Schou S.
        • Jensen T.S.
        • Zachariae R.
        • Svensson P.
        Specifying the nonspecific components of acupuncture analgesia.
        Pain. 2013; 154: 1659-1667
        • Vickers A.J.
        • Cronin A.M.
        • Maschino A.C.
        • Lewith G.
        • MacPherson H.
        • Foster N.E.
        • Sherman K.J.
        • Witt C.M.
        • Linde K.
        Acupuncture for chronic pain: Individual patient data meta-analysis.
        Arch Intern Med. 2012; 172: 1444-1453
        • Wang H.
        • Li K.Y.
        • Wu G.C.
        • Cao X.D.
        C-fos expression in spinal cord and brainstem following noxious stimulation and electroacupuncture plus noxious stimulation.
        Acupunct Electrother Res. 1995; 20: 163-172
        • Wang L.P.
        • Zhang X.Z.
        • Guo J.
        • Liu H.L.
        • Zhang Y.
        • Liu C.Z.
        • Yi J.H.
        • Zhao J.P.
        • Li S.S.
        Efficacy of acupuncture for migraine prophylaxis: A single-blinded, double-dummy, randomized controlled trial.
        Pain. 2011; 152: 1864-1871
        • Wang S.M.
        • Kain Z.N.
        • White P.
        Acupuncture analgesia, I: The scientific basis.
        Anesth Analg. 2008; 106: 602-610
        • Wang S.M.
        • Kain Z.N.
        • White P.F.
        Acupuncture analgesia, II: Clinical considerations.
        Anesth Analg. 2008; 106: 611-621
        • Yang C.P.
        • Wang N.H.
        • Li T.C.
        • Hsieh C.L.
        • Chang H.H.
        • Hwang K.L.
        • Ko W.S.
        • Chang M.H.
        A randomized clinical trial of acupuncture versus oral steroids for carpal tunnel syndrome: A long-term follow-up.
        J Pain. 2011; 12: 272-279
        • Zhao Z.Q.
        Neural mechanism underlying acupuncture analgesia.
        Prog Neurobiol. 2008; 85: 355-375
        • Zhu B.
        • Xu W.D.
        • Rong P.J.
        • Ben H.
        • Gao X.Y.
        A C-fiber reflex inhibition induced by electroacupuncture with different intensities applied at homotopic and heterotopic acupoints in rats selectively destructive effects on myelinated and unmyelinated afferent fibers.
        Brain Res. 2004; 1011: 228-237
        • Zimmermann M.
        Ethical guidelines for investigations of experimental pain in conscious animals.
        Pain. 1983; 16: 109-110