OJAnes  Vol.2 No.2 , April 2012
Serotonin Influences the Endogenous Opiate Peptides in the Rat Spinal Cord to Participates in Pain Modulation
Abstract: Spinal cord is a necessary pathway that transfers the body nociceptive inputs to the brain. Endogenous opiate peptides have been proven to participate in the nociceptive process at spinal level. It has reported that serotonin (5-HT, 5-hydroxytryptamine) in spinal cord plays a role in pan modulation, which can be blocked by opiate receptor antagonists. The present study was designed to investigate the interaction between 5-HT and endogenous opiate peptides at rat spinal level effecting on pain modulation. The results showed that 1) pain stimulation increased not only leucine-enkephalin (L-Ek), β-endorphin (β-Ep) and dynorphin A1-13 (DynA1-13) concentrations but also 5-HT and 5-hydorxyindoleace acid (5-HIAA, the 5-HT main metabolic product) concentrations in spinal cord significantly; 2) 5-HT could increase L-Ek, β-Ep and DynA1-13 concentrations in spinal cord in a dose-dependent manner, whereas cypotolamine (a 5-HT receptor antagonist) decreased L-Ek, β-Ep and DynA1-13 concentrations in spinal cord. The data suggested that 5-HT antinociceptive role might be involved in the endogenous opiate peptide system through 5-HT receptors at spinal level.
Cite this paper: Y. Pan, Z. Yin, J. Yang, Y. Zhao and D. Wang, "Serotonin Influences the Endogenous Opiate Peptides in the Rat Spinal Cord to Participates in Pain Modulation," Open Journal of Anesthesiology, Vol. 2 No. 2, 2012, pp. 29-35. doi: 10.4236/ojanes.2012.22008.

[1]   D. J. Walther, J. U. Peter, S. Bashammakh, H. Hortnagl, M. Voits, H. Fink and M. Bader, “Synthesis of Serotonin by a Second Tryptophan Hydroxylase Isoform,” Science, Vol. 299, 2003, p. 76. doi:10.1126/science.1078197

[2]   H. G. Lee, W. M. Kim, C. H. Park and M. H. Yoon, “Roles of Adenosine and Serotonin Receptors on the Antinociception of Sildenafil in the Spinal Cord of Rats,” Yonsei Medical Journal, Vol. 51, No. 6, 2010, pp. 960964. doi:10.3349/ymj.2010.51.6.960

[3]   Z. Song, C. Ultenius, B. A. Meyerson and B. Linderoth, “Pain Relief by Spinal Cord Stimulation Involves Serotonergic Mechanisms: An Experimental Study in a Rat Model of Mononeuropathy,” Pain, Vol. 147, No. 1, 2009, pp. 241-248. doi:10.1016/j.pain.2009.09.020

[4]   F.-Y. Liu, X.-X. Qu, X. Ding, J. Cai, H. Jiang, Y. Wan, J.-S. Han and G.-G. Xing, “Decrease in the Descending Inhibitory 5-HT System in Rats with Spinal Nerve Ligation,” Brain Research, Vol. 1330, 2010, pp. 45-60. doi:10.1016/j.brainres.2010.03.010

[5]   J. Hughes, T. W. Smith, H. W. Kosterlitz, L. A. Fothergill, B. A. Morgan and H. R. Morris, “Identification of Two Related Pentapeptides from the Brain with Potent Opiate Agonist Activity,” Nature, Vol. 258, 1975, pp. 577-580. doi:10.1038/258577a0

[6]   L. H. Lazarus, N. Ling and R. Guillemin, “β-Lipotropin as a Prohormone for the Morphinomimetic Peptides Endorphins and Enkephalins,” Proceedings of the National Academy of Sciences, Vol. 73, No. 6, 1976, pp. 2156-2159. doi:10.1073/pnas.73.6.2156

[7]   A. Goldstenin, S. Tachibana, L. I. Lowney, M. Hunkapiller and L. Hood, “Dynorphin-(1-13), an Extraordinarily Potent Opioid Peptide,” Proceedings of the National Academy of Sciences, Vol. 76, No. 12, 1979, pp. 6666-6670. doi:10.1073/pnas.76.12.6666

[8]   M. J. Millan and A. Herz, “The Endocrinology of the Opioids,” International Review of Neurobiology, Vol. 26, 1985, pp. 1-83. doi:10.1016/S0074-7742(08)60072-0

[9]   R. J. Bodnar, “Endogenous Opiates and Behavior: 2009,” Peptides, Vol. 31, No. 12, 2010, pp. 2325-2359. doi:10.1016/j.peptides.2010.09.016

[10]   A. Herz and M. J. Millan, “Opioids and Opioid Receptors Mediating Antinociception at Various Levels of the Neuraxis,” Physiol Bohemoslov, Vol. 39, No. 5, 1990, pp. 395-401.

[11]   J. P. Rosenfeld, “Interacting Brain Stem Components of Opiate-Activated, Descending, Pain-Inhibitory Systems,” Neuroscience & Biobehavioral Reviews, Vol. 18, No. 3, 1994, pp. 403-409. doi:10.1016/0149-7634(94)90053-1

[12]   J. A. Stamford, “Descending Control of Pain,” British Journal of Anaesthesia, Vol. 75, 1995, pp. 217-227.

[13]   Z.-Q. Zhao, “Neural Mechanism Underlying Acupuncture Analgesia,” Progress in Neurobiology, Vol. 85, No. 4, 2008, pp. 355-375. doi:10.1016/j.pneurobio.2008.05.004

[14]   S.-W. Yang, Z.-H. Zhang, R. Wang, Y.-F. Xie, J.-T. Qiao and N. Dafny, “Norepinephrine and Serotonin-Induced Antinociception Are Blocked by Naloxone with Different Dosages,” Brain Research Bulletin, Vol. 35, No. 2, 1994, pp. 113-117. doi:10.1016/0361-9230(94)90090-6

[15]   T. Crisp, J. L. Stafinsky, J. E. Hess and M. Uram, “Spinal β-Endorphin Analgesia Involves an Interaction with Local Monoaminergic Systems,” European Journal of Pharmacology, Vol. 160, No. 2, 1989, pp. 211-217. doi:10.1016/0014-2999(89)90493-7

[16]   M. O. Carruba, E. Nisoli, V. Garosi, P. Sacerdote, A. E. Panerai and M. da Prada, “Catecholamine and Serotonin Depletion from Rat Spinal Cord: Effects on Morphine and Footshock Induced Analgesia,” Pharmacological Research, Vol. 25, No. 2, 1992, pp. 187-194. doi:10.1016/1043-6618(92)91387-V

[17]   G. González-Mariscal, P. Gómora and C. Beyer, “Participation of Opiatergic, GABAergic, and Serotonergic Systems in the Expression of Copulatory Analgesia in Male Rats,” Pharmacology Biochemistry and Behavior, Vol. 49, No. 2, 1994, pp. 303-307. doi:10.1016/0091-3057(94)90425-1

[18]   M. Zimmermann, “Ethical Guidelines for Investigations of Experimental Pain in Conscious Animal,” Pain, Vol. 16, No. 2, 1983, pp. 109-110. doi:10.1016/0304-3959(83)90201-4

[19]   J. W. Silveira, Q. M. Dias, E. A. Del Bel and W. A. Prado, “Serotonin Receptors Are Involved in the Spinal Mediation of Descending Facilitation of Surgical Incision-Induced Increase of Fos-Like Immunoreactivity in Rats,” Molecular Pain, Vol. 6, 2010, p. 17. doi:10.1186/1744-8069-6-17

[20]   O. Yanarates, A. Dogrul, V. Yildirim, A. Sahin, A. Sizlan, M. Seyrek, O. Akgül, O. Kozak, E. Kurt and U. Aypar, “Spinal 5-HT7 Receptors Play an Important Role in the Antinociceptive and Antihyperalgesic Effects of Tramadol and Its Metabolite, O-Desmethyltramadol, via Activation of Descending Serotonergic Pathways,” Anesthesiology, Vol. 112, No. 3, 2010, pp. 696-710. doi:10.1097/ALN.0b013e3181cd7920

[21]   Y.-J. Li, Z.-H. Zhang, J.-Y. Chen and J.-T. Qiao, “Effects of Intrathecal Naloxone and Atropine on the Nociceptive Suppression Induced by Norepinephrine and Serotonin at the Spinal Level in Rats,” Brain Research, Vol. 666, No. 1, 1994, pp. 113-116. doi:10.1016/0006-8993(94)90290-9

[22]   A. H. Lichtman and M. S. Fanselow, “Opioid and Nonopioid Conditional Analgesia: The Role of Spinal Opioid, Noradrenergic, and Serotonergic Systems,” Behavioral Neuroscience, Vol. 105, No. 5, 1991, pp. 687-698. doi:10.1037/0735-7044.105.5.687

[23]   K. Nakatani, L. M. Kitahata, Y. Harada, K. Omote, J. G. Collins and O. Yuge, “Interaction between Opiate Subtypes and Serotonin in Suppressing Noxiously Evoked Activity of WDR Neurons,” Nihon Masui Igakai, Vol. 44, No. 6, 1995, pp. 795-799.

[24]   J. Yang, H. F. Yuan, J. G. Chu, Y. Yang, H. T. Xu, G. Wang, W. Y. Liu and B. C. Lin, “Arginine Vasopressin Antinociception in the Rat Nucleus Raphe Magnus Is Involved in the Endogenous Opiate Peptide and Serotonin System,” Peptides, Vol. 30, No. 7, 2009, pp. 1355-1361. doi:10.1016/j.peptides.2009.03.014

[25]   N. Wijnvoord, B. Albuquerque, A. Haussler, T. Myrczek, L. Popp and I. Tegeder, “Inter-Strain Differences of Serotonergic Inhibitory Pain Control in Inbred Mice,” Molecular Pain, Vol. 6, 2010, p. 70. doi:10.1186/1744-8069-6-70

[26]   L. A. Bero and C. M. Kuhn, “Role of Serotonin in Opiate-Induced Prolactin Secretion and Antinociception in the Developing Rat,” Journal of Pharmacology Exprimental Therapeutics, Vol. 240, No. 3, 1987, pp. 831-836.