Antinociceptive effect of intrathecal administration of taurine in rat models of neuropathic pain

  • Tadanori Terada
  • Koji Hara
  • Yasunori Haranishi
  • Takeyoshi Sata
Reports of Original Investigations



Taurine is the most abundant amino acid in many tissues. Although taurine has been shown to be antinociceptive, in this report, our focus is to elucidate the mechanism and action site on neuropathic pain. This study used behavioural assessments to determine whether taurine attenuates neuropathic pain in the spinal cord.


Chronic constriction injury (CCI) to the sciatic nerve and streptozotocin-induced diabetic neuropathy were introduced to male Sprague-Dawley rats. We then assessed the antinociceptive effect of spinal injections of taurine (100, 200, 400, or 800 μg) using electronic von Frey, paw pressure, and plantar tests. To explore the effect of taurine on motor function, a rotarod test was performed, and in order to determine which neurotransmitter pathway is involved in taurine’s action, we examined how several antagonists of spinal pain processing receptors altered the effect of taurine 400 μg in a paw pressure test.


Taurine alleviated mechanical allodynia, mechanical hyperalgesia, and thermal hyperalgesia in CCI rats and suppressed mechanical allodynia and hyperalgesia in diabetic rats. Significant effects were observed at 200 μg in both models. On the other hand, taurine dose-dependently affected motor performance, and a significant effect was seen at 400 μg. The antinociceptive effects were reversed completely by pretreatment with an intrathecal injection of strychnine, a glycine receptor antagonist.


The present study demonstrated that intrathecal administration of taurine attenuates different models of neuropathic pain, and these effects seem to be mediated by the activation of glycinergic neurotransmission. These findings suggest that taurine may be a candidate remedy for neuropathic pain.


Taurine Neuropathic Pain Mechanical Allodynia Chronic Constriction Injury Thermal Hyperalgesia 

Effet antinociceptif d’une administration intrathécale de taurine dans un modèle de douleur neuropathique chez le rat



La taurine est l’acide aminé le plus abondant dans plusieurs tissus. Bien qu’il ait été démontré que la taurine a un effet antinociceptif, notre objectif dans ce compte-rendu est d’explorer son mécanisme et son site d’action dans les cas de douleur neuropathique. Cette étude s’est fondée sur des évaluations comportementales afin de déterminer si la taurine atténue la douleur neuropathique dans la moelle épinière.


Des lésions de constriction chronique (chronic constriction injury ou CCI) du nerf sciatique et une neuropathie diabétique induite par la streptozotocine ont été introduites à des rats Sprague-Dawley mâles. Nous avons ensuite évalué l’effet antinociceptif d’injections rachidiennes de taurine (100, 200, 400, ou 800 μg) à l’aide du test électronique de von Frey, du test de pression sur la patte et de tests plantaires. Afin d’explorer l’effet de la taurine sur la fonction motrice, un test de la tige tournante a été réalisé. Dans le but de déterminer quelle voie de neurotransmission était impliquée dans l’action de la taurine, nous avons examiné la façon dont plusieurs antagonistes des récepteurs médiant la douleur rachidienne ont modifié l’effet de la taurine à la dose de 400 μg dans un test de pression sur la patte.


La taurine a soulagé l’allodynie mécanique, l’hyperalgésie mécanique et l’hyperalgésie thermique chez les rats en CCI et supprimé l’allodynie mécanique et l’hyperalgésie dans les modèles de rats diabétiques. Des effets significatifs ont été observés lors de l’administration de doses de 200 μg dans les deux modèles. D’autre part, la taurine a affecté la performance motrice de façon dose-dépendante, et un effet significatif a été observé à 400 μg. Les effets antinociceptifs ont été complètement neutralisés par un pré-traitement à l’aide d’une injection intrathécale de strychnine, un antagoniste du récepteur de la glycine.


Cette étude a démontré que l’administration intrathécale de taurine atténue différents modèles de douleur neuropathique, et ces effets semblent être médiés par l’activation de la neurotransmission glycinergique. Ces résultats suggèrent que la taurine pourrait être un candidat pour le traitement de la douleur neuropathique.



This study was supported in part by Grants-in-Aid for Research from the Ministry of Education, Science and Culture of Japan (No. 19791095 to K.H.).

Competing interests

None declared.


  1. 1.
    Banerjee R, Vitvitsky V, Garg SK. The undertow of sulfur metabolism on glutamatergic neurotransmission. Trends Biochem Sci 2008; 33: 413-9.CrossRefGoogle Scholar
  2. 2.
    Gupta RC. Taurine analogues and taurine transport: therapeutic advantages. Adv Exp Med Biol 2006; 583: 449-67.CrossRefGoogle Scholar
  3. 3.
    Albrecht J, Schousboe A. Taurine interaction with neurotransmitter receptors in the CNS: an update. Neurochem Res 2005; 30: 1615-21.CrossRefGoogle Scholar
  4. 4.
    Serrano MI, Serrano JS, Guerrero MR, Fernandez A. Role of GABAA and GABAB receptors and peripheral cholinergic mechanisms in the antinociceptive action of taurine. Gen Pharmacol 1994; 25: 1123-9.CrossRefGoogle Scholar
  5. 5.
    Silva MA, Cunha GM, Viana GS, Rao VS. Taurine modulates chemical nociception in mice. Braz J Med Biol Res 1993; 26: 1319-24.PubMedGoogle Scholar
  6. 6.
    Smullin DH, Schamber CD, Skilling SR, Larson AA. A possible role for taurine in analgesia. Prog Clin Biol Res 1990; 351: 129-32.PubMedGoogle Scholar
  7. 7.
    Li F, Obrosova IG, Abatan O, et al. Taurine replacement attenuates hyperalgesia and abnormal calcium signaling in sensory neurons of STZ-D rats. Am J Physiol Endocrinol Metab 2005; 288: E29-36.CrossRefGoogle Scholar
  8. 8.
    Belfer I, Davidson E, Ratner A, Beery E, Shir Y, Seltzer Z. Dietary supplementation with the inhibitory amino acid taurine suppresses autotomy in HA rats. Neuroreport 1998; 9: 3103-7.CrossRefGoogle Scholar
  9. 9.
    Pellicer F, Lopez-Avila A, Coffeen U, Manuel Ortega-Legaspi J, Angel RD. Taurine in the anterior cingulate cortex diminishes neuropathic nociception: a possible interaction with the glycine(A) receptor. Eur J Pain 2007; 11: 444-51.CrossRefGoogle Scholar
  10. 10.
    Zeilhofer HU. The glycinergic control of spinal pain processing. Cell Mol Life Sci 2005; 62: 2027-35.CrossRefGoogle Scholar
  11. 11.
    Zeilhofer HU, Zeilhofer UB. Spinal dis-inhibition in inflammatory pain. Neurosci Lett 2008; 437: 170-4.CrossRefGoogle Scholar
  12. 12.
    Enna SJ, McCarson KE. The role of GABA in the mediation and perception of pain. Adv Pharmacol 2006; 54: 1-27.CrossRefGoogle Scholar
  13. 13.
    Yaksh TL, Rudy TA. Chronic catheterization of the spinal subarachnoid space. Physiol Behav 1976; 17: 1031-6.CrossRefGoogle Scholar
  14. 14.
    Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988; 33: 87-107.CrossRefGoogle Scholar
  15. 15.
    Randall LO, Selitto JJ. A method for measurement of analgesic activity on inflamed tissue. Arch Int Pharmacodyn Ther 1957; 111: 409-19.PubMedGoogle Scholar
  16. 16.
    Hargreaves K, Dubner R, Brown F, Flores C, Joris J. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 1988; 32: 77-88.CrossRefGoogle Scholar
  17. 17.
    Haranishi Y, Hara K, Terada T, Nakamura S, Sata T. The antinociceptive effect of intrathecal administration of glycine transporter-2 inhibitor ALX1393 in a rat acute pain model. Anesth Analg 2010; 110: 615-21.CrossRefGoogle Scholar
  18. 18.
    Malcangio M, Tomlinson DR. A pharmacologic analysis of mechanical hyperalgesia in streptozotocin/diabetic rats. Pain 1998; 76: 151-7.CrossRefGoogle Scholar
  19. 19.
    Fox A, Eastwood C, Gentry C, Manning D, Urban L. Critical evaluation of the streptozotocin model of painful diabetic neuropathy in the rat. Pain 1999; 81: 307-16.CrossRefGoogle Scholar
  20. 20.
    Huang W, Simpson RK. Long-term intrathecal administration of glycine prevents mechanical hyperalgesia in a rat model of neuropathic pain. Neurol Res 2000; 22: 160-4.CrossRefGoogle Scholar
  21. 21.
    Johnson JW, Ascher P. Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature 1987; 325: 529-31.CrossRefGoogle Scholar
  22. 22.
    Kim HK, Park SK, Zhou JL, et al. Reactive oxygen species (ROS) play an important role in a rat model of neuropathic pain. Pain 2004; 111: 116-24.CrossRefGoogle Scholar
  23. 23.
    Hacimuftuoglu A, Handy CR, Goettl VM, Lin CG, Dane S, Stephens RL Jr. Antioxidants attenuate multiple phases of formalin-induced nociceptive response in mice. Behav Brain Res 2006; 173: 211-6.CrossRefGoogle Scholar
  24. 24.
    Baron R. Neuropathic pain: a clinical perspective. Handb Exp Pharmacol 2009; 194: 3-30.CrossRefGoogle Scholar
  25. 25.
    Dray A. Neuropathic pain: emerging treatments. Br J Anaesth 2008; 101: 48-58.CrossRefGoogle Scholar
  26. 26.
    Munro G, Ahring PK, Mirza NR. Developing analgesics by enhancing spinal inhibition after injury: GABAA receptor subtypes as novel targets. Trends Pharmacol Sci 2009; 30: 453-9.CrossRefGoogle Scholar
  27. 27.
    Lynch JW. Molecular structure and function of the glycine receptor chloride channel. Physiol Rev 2004; 84: 1051-95.CrossRefGoogle Scholar

Copyright information

© Canadian Anesthesiologists' Society 2011

Authors and Affiliations

  • Tadanori Terada
    • 1
  • Koji Hara
    • 1
  • Yasunori Haranishi
    • 1
  • Takeyoshi Sata
    • 1
  1. 1.Department of AnesthesiologyUniversity of Occupational and Environmental Health, School of MedicineKitakyushuJapan

Personalised recommendations