Skip to main content
SpringerLink
Log in

Spinal 5-HT pathways and the antinociception induced by intramedullary clonidine in rats

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

The possible involvement of spinal 5-hydroxytryptamine (5-HT) pathways in antinociception induced by microinjection of clonidine into the ventrolateral surface of the medulla oblongata was investigated in rats. Microinjection of clonidine (10-20 µg), but not yohimbine (1 µg) or 0.9% saline, into the lateral medulla prolonged the hot plate latency in rats. This clonidine-induced antinociception was abolished by intramedullary injection of the alpha2-adrenoceptor antagonist, yohimbine. Selective destruction of spinal 5-HT neurons produced by intraspinal injection of 5,7-dihydroxytryptamine (5,7-DHT; 10 µg) or postsynaptic blockade of spinal 5-HT receptors produced by intrathecal injection of cyproheptadine (1 µg; a mixed 5-HT1/5-HT2 antagonist) also abolished clonidine-induced antinociception. Rats given 5,7-DHT intraspinally or cyproheptadine intrathecally showed a decrease in hot plate latency as compared with the controls. In anesthetized rats, the 5-HT release from the thoracic spinal cord was enhanced by microinjection of clonidine into the lateral medulla. This enhanced spinal 5-HT release evoked by intramedullary injection of clonidine was abolished by pretreatment of rats with intraspinal injection of 5,7-DHT. These results indicate that 5-HT pathways to the spinal cord mediate the antinociceptive effect induced by microinjection of clonidine into the ventrolateral surface of the medulla oblongata in rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Amendt K, Czachurski J, Dembowsky K, Seller H (1978) Neurons within the ‘chemosensitive area’ on the ventral surface of the brainstem which project to the intermediolateral column. Pflügers Arch 375:289–292

    Google Scholar 

  • Basbaum AI, Fields HL (1978) Endogenous pain control mechanisms: Review and hypothesis. Ann Neurol 4:451–462

    Google Scholar 

  • Bently GA, Copeland IW, Starr J (1977) The actions of some alpha-adrenoceptor agonists and antagonists in an antinociceptive test in mice. Clin Exp Pharmacol Physiol 5:405–419

    Google Scholar 

  • Cahusac P, Hayes AG, Skingle M, Tyers MB (1981) Studies on the antinociceptive effects of clonidine and 4-hydroxyclonidine in the rat. Br J Pharmac 74:963–964

    Google Scholar 

  • Crespi F, Martin KF, Marsden CA (1988) Measurement of extracellular basal levels of serotonin in vivo using nafion-coated carbon fibre electrodes combined with differential pulse voltammetry. Neuroscience 27:885–896

    Google Scholar 

  • Curtis AL, Marwah J (1985) Central alpha-2-adrenoceptors mediate the nociceptive jaw-opening reflex. Soc Neurosci Abstr 11:1044

    Google Scholar 

  • Duan J, Sawynok J (1987 Enhancement of clonidine-induced analgesia by lesions induced with spinal and intracerebroventricular administration of 5,7-dihydroxytryptamine. Neuropharmacology 26: 323–329

    Google Scholar 

  • Fasmer OB, Berge OG, Walther B, Hole K (1983) Changes in nociception after intrathecal administration of 5,6-dihydroxytryptamine. Neuropharmacology 22:1197–1202

    Google Scholar 

  • Fielding S, Wilker J, Hynes M, Szewczak M, Novick WJ, Lal H (1978) A comparison of clonidine with morphine for antinociceptive and antiwithdrawal actions. J Pharmacol Exp Ther 207:899–905

    Google Scholar 

  • Fielding S, Spaulding TC, Lal H (1981) Antinociceptive actions of clonidine. In: Progress in clinical and biological research, psychopharmacology of clonidine. New York, pp 225–242

  • Fields HL, Heinricher MM, Mason P (1991) Neurotransmitters in nociceptive modulatory circuits. Annu Rev Neurosci 14:219–245

    Google Scholar 

  • Haubrich DR, Mastriani D, Ferraino R, Ferrari R, Perrone M, Trethaway L, Knapp T, Burns A (1982) Role of alpha-2 adrenergic mechanisms in nociception. Soc Neurosci Abstr 8:485

    Google Scholar 

  • Ho MT, Young MS, Lin MT, Fan IJ (1990) Calibration and testing of multiple carbon fiber electrode for in vivo dopamine measurement via differential pulse amperometry. Proc Far Eastern Conf on Med and Biol Engineering (FECMB), pp 104–105

  • Howe PRC, Kuhn DM, Minson JB, Stead BH, Chalmers JP (1983) Evidence for a bulbospinal serotonergic pressor pathway in the rat brain. Brain Res 270:29–36

    Google Scholar 

  • Howe JR, Yaksh TL (1982) Changes in sensitivity to intrathecal norepinephrine and serotonin after 6-hydroxydopamine (6-OHDA), 5,6-dihydroxytryptamine (5,6-DHT) or repeated monoamine administration. J Pharmacol Exp Ther 220:311–321

    Google Scholar 

  • Hutson PH, Tricklebank MD, Curzon G (1982) Enhancement of footshock-induced analgesia by spinal 5,7-dihydroxytryptamine lesions. Brain Res 237:367–372

    Google Scholar 

  • Kuraishi Y, Harada Y, Aratani S, Satoh M, Takagi H (1983) Separate involvement of the spinal noradrenergic and serotonergic systems in morhpine analgesia: the difference in mechanical and thermal algesic tests. Brain Res 273:245–252

    Google Scholar 

  • Lin MT, Chi ML, Chandra A, Tsay BL (1980) Serotoninergic mechanisms of beta-endorphin- and clonidine-induced analgesia in rats. Pharmacology 20:323–328

    Google Scholar 

  • Lin MT, Wu JJ, Tsay BL (1984) Effects of kainic acid injections in the striatum on physiological and behavioral functions in conscious rats. Exp Neurol 83:71–83

    Google Scholar 

  • Liu MY, Su CF, Lin MT (1988) The antinociceptive role of a bulbospinal serotonergic pathway in the rat brain. Pain 33:123–129

    Google Scholar 

  • Loewy AD, McKellar S (1981) Serotonergic projections form the ventral medulla to the intermediolateral cell column in the rat. Brain Res 211:146–152

    Google Scholar 

  • Marcenac F, Gonon FG (1985) Fast in vivo monitoring of dopamine release in the rat brain with differential pulse amperometry. Anal Chem 57:1778–1779

    Google Scholar 

  • McLeary PE, Leander JD (1981) Clonidine analgesia and suppression of operant responding: Dissociation of mechanism. Eur J Pharmac 69:63–69

    Google Scholar 

  • Milne B, Cervenko FW, Jhamandas K, Sutak M (1985) Intrathecal clonidine: Analgesia and effect on opiate withdrawal in the rat. Anesthesiology 62:34–38

    Google Scholar 

  • Paalzow L (1974) Analgesia produced by clonidine in mice and rats. J Pharm Pharmac 26:361–363

    Google Scholar 

  • Paalzow G, Paalzow L (1976) Clonidine antinociceptive activity: effects of drugs influencing central monoaminergic and cholinergic mechanisms in the rat. Arch Pharmacol 292:119–126

    Google Scholar 

  • Paalzow GHM, Paalzow LK (1982) Separate noradrenergic receptors could mediate clonidine antinociception. J Pharmac Exp Ther 223:795–800

    Google Scholar 

  • Pellegrino LJ, Pellegrino AS, Cushman AJ (1979) A stereotaxic atlas of the rat brain, 2nd edn. Plenum Press, New York

    Google Scholar 

  • Proudfit HK, Hammond DL (1981) Alterations in nociceptive threshold and morphine-induced analgesia produced by intrathecally administered amine antagonists. Brain Res 218:393–399

    Google Scholar 

  • Proudfit HK, Yaksh TL (1980) Alterations in nociceptive and morphine-induced analgesia following the selective depletion of spinal cord monoamines. Soc Neurosci Abstr 6:433

    Google Scholar 

  • Reddy SVR, Maderdrut JL, Yaksh TL (1980) Spinal cord pharmacology of adrenergic agonist-mediated antinociception. J Pharmac Exp Ther 213:525–533

    Google Scholar 

  • Ross CA, Ruggiero DA, Reis DJ (1981) Projections form neurons close to the ventral surface of the hindbrain to the spinal cord in the rat. Neurosci Lett 21:143–148

    Google Scholar 

  • Sagen J, Proudfit HD (1985) Evidence for pain modulation by pre- and postsynaptic noradrenergic receptors in the medulla oblongata: Brain Res 331:285–293

    Google Scholar 

  • Sawynok J, Dickson C (1985) Evidence for the involvement of descending noradrenergic pathway in the antinociceptive effect of baclofen. Brain Res 335:89–97

    Google Scholar 

  • Sawynok J, Reid A (1986) Role of ascending and descending noradrenergic pathways in the antinociceptive effect of baclofen and clonidine. Brain Res 386:341–350

    Google Scholar 

  • Schmitt H, Le Douarec JC, Petillot N (1974) Antinociceptive effect of some alpha-sympathomimetic agents. Neuropharmacology 13:289–294

    Google Scholar 

  • Spaulding TC, Venafro JJ, Ma MG, Fielding S (1979) The dissociation of the antinociceptive effect of clonidine from supraspinal structures. Neuropharmacology 18:103–105

    Google Scholar 

  • Wang YC, Su CF, Lin MT (1985) The site and the mode of analgesic actions exerted by clonidine in monkeys. Exp Neurol 90:479–488

    Google Scholar 

  • Yaksh TL, Hammond DL, Tyce GM (1981) Functional aspects of bulbospinal monoaminergic projection in modulating processing of somatosensory information. Fed Proc 40:2786–2794

    Google Scholar 

  • Young MS, Ho MT, Lin MT (1989) Fabrication and electrochemical treatment of the carbon fiber electrode in the neurotransmitters measurement via voltammetry. IEEE/11th Ann Conf of Engineering in Med and Biol Soc, pp 1130–1131

  • Zemlan FP, Corrigan SA, Pfaff DW (1980) Noradrenergic and serotonergic mediation of spinal analgesia mechanisms. Eur J Pharmac 61:111–124

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, National Cheng Kung University Medical College, Tainan City, Taiwan, Republic of China

    M. T. Lin

  2. Department of Surgery, National Defense Medical Center, Taipei, Taiwan, Republic of China

    C. F. Su

Authors
  1. M. T. Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. F. Su
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This study was supported by grants from the National Science Council (Taipei, Taiwan, Republic of China)

Send offprint requests to M.T. Lin at the above address

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lin, M.T., Su, C.F. Spinal 5-HT pathways and the antinociception induced by intramedullary clonidine in rats. Naunyn-Schmiedeberg's Arch Pharmacol 346, 333–338 (1992). https://doi.org/10.1007/BF00173548

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00173548

Key words

Search

Navigation