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Involvement of Spinal Serotonin Receptors in Electroacupuncture Anti-Hyperalgesia in an Inflammatory Pain Rat Model

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Abstract

We previously showed that electroacupuncture (EA) activates medulla-spinal serotonin-containing neurons. The present study investigated the effects of intrathecal 5,7-dihydroxytryptamine creatinine sulfate, a selective neurotoxin for serotonergic terminals, the 5-hydroxytryptamine 1A receptor (5-HT1AR) antagonist NAN-190 hydrobromide and the 5-HT2C receptor (5-HT2CR) antagonist SB-242,084 on EA anti-hyperalgesia. EA was given twice at acupoint GB30 after complete Freund’s adjuvant (CFA) injection into hind paw. CFA-induced hyperalgesia was measured by assessing hind paw withdrawal latency (PWL) to a noxious thermal stimulus 30 min post-EA. Serotonin depletion and the 5-HT1AR antagonist blocked EA anti-hyperalgesia; the 5-HT2CR antagonist did not. Immunohistochemical staining showed that spinal 5-HT1AR was expressed and that 5-HT2CR was absent in naive and CFA-injected animals 2.5 h post-CFA. These results show a correlation between EA anti-hyperalgesia and receptor expression. Collectively, the data show that EA activates supraspinal serotonin neurons to release 5-HT, which acts on spinal 5-HT1AR to inhibit hyperalgesia.

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References

  1. Cheng X (1999) Chinese acupuncture and moxibustion. Foreign Languages Press, Beijing

    Google Scholar 

  2. Bullock ML, Pheley AM, Kiresuk TJ, Lenz SK, Culliton PD (1997) Characteristics and complaints of patients seeking therapy at a hospital-based alternative medicine clinic. J Altern Complement Med 3:31–37

    Article  PubMed  CAS  Google Scholar 

  3. Diehl DL, Kaplan G, Coulter I, Glik D, Hurwitz EL (1997) Use of acupuncture by American physicians. J Altern Complement Med 3:119–126

    Article  PubMed  CAS  Google Scholar 

  4. Zhao Z (2008) Neural mechanism underlying acupuncture analgesia. Prog Neurobiol 85:355–375

    Article  PubMed  Google Scholar 

  5. Lao L, Zhang R-X, Zhang G, Wang X, Berman BM, Ren K (2004) A parametric study of electroacupuncture on persistent hyperalgesia and Fos protein expression in rats. Brain Res 1020:18–29

    Article  PubMed  CAS  Google Scholar 

  6. Yang E, Koo S, Kim Y, Lee J, Hwang H, Lee M, Choi S (2010) Contralateral electroacupuncture pretreatment suppresses carrageenan-induced inflammatory pain via the opioid-mu receptor. Rheumatol Int. Feb 4. [Epub ahead of print]

  7. Zhang Y-Q, Ji G-C, Wu G-C, Zhao Z-Q (2002) Excitatory amino acid receptor antagonists and electroacupuncture synergetically inhibit carrageenan-induced behavioral hyperalgesia and spinal fos expression in rats. Pain 99:525–535

    Article  PubMed  CAS  Google Scholar 

  8. Koo ST, Park YI, Lim KS, Chung K, Chung JM (2002) Acupuncture analgesia in a new rat model of ankle sprain pain. Pain 99:423–431

    Article  PubMed  Google Scholar 

  9. Li A, Wang Y, Xin J, Lao L, Ren K, Berman BM, Zhang R-X (2007) Electroacupuncture suppresses hyperalgesia and spinal Fos expression by activating the descending inhibitory system. Brain Res 1186:171–179

    Article  PubMed  CAS  Google Scholar 

  10. Zhang M, Han JS (1985) 5-hydroxytryptamine is an important mediator for both high and low frequency electroacupuncture analgesia. Acupuncture Res 10:212–215

    CAS  Google Scholar 

  11. Han CS, Chou PH, Lu CC, Lu LH, Yang TH, Jen MF (1979) The role of central 5-hydroxytryptamine in acupuncture analgesia. Sci Sin 22:91–104

    PubMed  CAS  Google Scholar 

  12. Chang FC, Tsai HY, Yu MC, Yi PL, Lin JG (2004) The central serotonergic system mediates the analgesic effect of electroacupuncture on ZUSANLI (ST36) acupoints. J Biomed Sci 2004(11):179–185

    Google Scholar 

  13. Baek YH, Choi DY, Yang HI, Park DS (2005) Analgesic effect of electroacupuncture on inflammatory pain in the rat model of collagen-induced arthritis: mediation by cholinergic and serotonergic receptors. Brain Res 1057:181–185

    Article  PubMed  CAS  Google Scholar 

  14. Takagi J, Sawada T, Yonehara N (1996) A possible involvement of monoaminergic and opioidergic systems in the analgesia induced by electro-acupuncture in rabbits. Jpn J Pharmacol 70(1):73–80

    Article  PubMed  CAS  Google Scholar 

  15. Kim SK, Park JH, Bae SJ, Kim JH, Hwang BG, Min B-I, Park DS, Na HS (2005) 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

    Article  PubMed  CAS  Google Scholar 

  16. Buritova J, Larrue S, Aliaga M, Besson J-M, Colpaert F (2005) Effects of the high-efficacy 5-HT1A receptor agonist, F 13640 in the formalin pain model: a c-Fos study. Eur J Pharmacol 514:121–130

    PubMed  CAS  Google Scholar 

  17. Huang JC, Peroutka SJ (1987) Identification of 5-hydroxytryptamine1 binding site subtypes in rat spinal cord. Brain Res 436:173–176

    Article  PubMed  CAS  Google Scholar 

  18. Marlier L, Teilhac JR, Cerruti C, Privat A (1991) Autoradiographic mapping of 5-HT1, 5-HT1A, 5-HT1B and 5-HT2 receptors in the rat spinal cord. Brain Res 550:15–23

    Article  PubMed  CAS  Google Scholar 

  19. Fonseca MI, Ni YG, Dunning DD, Miledi R (2001) Distribution of serotonin 2A, 2C and 3 receptor mRNA in spinal cord and medulla oblongata. Mol Brain Res 89:11–19

    Article  PubMed  CAS  Google Scholar 

  20. Wei F, Dubner R, Ren K, Wei F, Dubner R, Ren K (1999) Nucleus reticularis gigantocellularis and nucleus raphe magnus in the brain stem exert opposite effects on behavioral hyperalgesia and spinal Fos protein expression after peripheral inflammation. Pain 80:127–141

    Article  PubMed  CAS  Google Scholar 

  21. Hung KC, Wu HE, Mizoguchi H, Leitermann R, Tseng LF (2003) Intrathecal treatment with 6-hydroxydopamine or 5, 7-dihydroxytryptamine blocks the antinociception induced by endomorphin-1 and endomorphin-2 given intracerebroventricularly in the mouse. J Pharmacol Sci 93:299–306

    Article  PubMed  CAS  Google Scholar 

  22. Hargreaves K, Dubner R, Brown F, Flores C, Joris J (1988) A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 32:77–88

    Article  PubMed  CAS  Google Scholar 

  23. Xu R, Guan X, Wang C (1993) Influence of capsaicin treating sciatic nerve on the pain threshold and the effect of acupuncture analgesia of rats. Acupuncture Res 18:280–284

    CAS  Google Scholar 

  24. Lao L, Zhang G, Wei F, Berman BM, Ren K (2001) Electroacupuncture attenuates behavioral hyperalgesia and selectively reduces spinal Fos protein expression in rats with persistent inflammation. J Pain 2:111–117

    Article  PubMed  CAS  Google Scholar 

  25. Iwa M, Matsushima M, Nakade Y, Pappas TN, Fujimiya M, Takahashi T (2006) Electroacupuncture at ST-36 accelerates colonic motility and transit in freely moving conscious rats. Am J Physiol Gastrointest Liver Physiol 290:G285–G292

    Article  PubMed  CAS  Google Scholar 

  26. Lao L, Hamilton GR, Fu J, Berman BM (2003) Is acupuncture safe? A systematic review of case reports. Altern Ther Health Med 9:72–83

    PubMed  Google Scholar 

  27. MacPherson H, Thomas K, Walters S, Fitter M (2001) A prospective survey of adverse events and treatment reactions following 34, 000 consultations with professional acupuncturists. Acupunct Med 19:93–102

    Article  PubMed  CAS  Google Scholar 

  28. Maeda Y, Lisi TL, Vance CGT, Sluka KA (2007) Release of GABA and activation of GABAA in the spinal cord mediates the effects of TENS in rats. Brain Res 1136:43–50

    Article  PubMed  CAS  Google Scholar 

  29. Zemlan FP, Murphy AZ, Behbehani MM (1994) 5-HT1A receptors mediate the effect of the bulbospinal serotonin system on spinal dorsal horn nociceptive neurons. Pharmacology 48:1–10

    Article  PubMed  CAS  Google Scholar 

  30. Abe K, Kato G, Katafuchi T, Tamae A, Furue H, Yoshimura M (2009) Responses to 5-HT in morphologically identified neurons in the rat substantia gelatinosa in vitro. Neuroscience 159:316–324

    Article  PubMed  CAS  Google Scholar 

  31. Yin H, Park SA, Han SK, Park SJ (2011) Effects of 5-hydroxytryptamine on substantia gelatinosa neurons of the trigeminal subnucleus caudalis in immature mice. Brain Res 1368:91–101

    Article  PubMed  CAS  Google Scholar 

  32. Sharma A, Punhani T, Fone KC (1997) Distribution of the 5-hydroxytryptamine2C receptor protein in adult rat brain and spinal cord determined using a receptor-directed antibody: effect of 5, 7-dihydroxytryptamine. Synapse 27:45–56

    Article  PubMed  CAS  Google Scholar 

  33. Han J-S (2003) Acupuncture neuropeptide release produced by electrical stimulation of different frequencies. Trends Neurosci 26:17–22

    Article  PubMed  CAS  Google Scholar 

  34. Zhang R-X, Lao L, Wang L, Liu B, Wang X, Ren K, Berman BM (2004) Involvement of opioid receptors in electroacupuncture-produced anti-hyperalgesia in rats with peripheral inflammation. Brain Res 1020:12–17

    Article  PubMed  CAS  Google Scholar 

  35. Kim JH, Min B-I, Na HS, Park DS (2004) Relieving effects of electroacupuncture on mechanical allodynia in neuropathic pain model of inferior caudal trunk injury in rat: mediation by spinal opioid receptors. Brain Res 998:230–236

    Article  PubMed  CAS  Google Scholar 

  36. Kellstein DE, Malseed RT, Goldstein FJ (1988) Opioid-monoamine interactions in spinal antinociception: evidence for serotonin but not norepinephrine reciprocity. Pain 34:85–92

    Article  PubMed  CAS  Google Scholar 

  37. Yang SW, Zhang ZH, Wang R, Xie YF, Qiao JT, Dafny N (1994) Norepinephrine and serotonin-induced antinociception are blocked by naloxone with different dosages. Brain Res Bull 35:113–117

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by NIH Grant R21AT004113 and P01 AT002605. We would like to thank Dr. Lyn Lowry for her editorial support.

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Correspondence to Rui-Xin Zhang.

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Zhang, Y., Li, A., Xin, J. et al. Involvement of Spinal Serotonin Receptors in Electroacupuncture Anti-Hyperalgesia in an Inflammatory Pain Rat Model. Neurochem Res 36, 1785–1792 (2011). https://doi.org/10.1007/s11064-011-0495-1

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