Skip to main content
Log in

Intrathecal Adenosine A1 Receptor Agonist Attenuates Hyperalgesia Without Inhibiting Spinal Glutamate Release in the Rat

  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

The analgesia effects of intrathecal adenosine A1 receptor agonist, R-PIA, on the hyperalgesia and CSF-glutamate release after formalin injection into the rat paw were evaluated. R-PIA significantly and dose-dependently attenuated increases in flinching behavior, and this attenuating effect was reversed by the adenosine A1 receptor antagonist, aminophylline. Morphine blocked flinchs, however MK-801 partially abolished. The increase in CSF-glutamate release evoked by formalin stimulation was inhibited by morphine but not by either R-PIA or MK-801. These findings suggest that the intrathecal adenosine A1 receptor agonist provokes analgesic effect via the postsynaptic action independent of an effect upon spinal glutamate release.

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

Access this article

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

  • Cahill, C. M., White, T. D., and Sawynok, J. (1995). Spinal opioid receptors and adenosine release: Neurochemical and behavioral characterization of opioid subtypes. J. Pharmacol. Exp. Ther. 275:84–93.

    Google Scholar 

  • Choca, J. I., Green, R. D., and Proudfit, H. K. (1988). Adenosine A1 and A2 receptors of the substantia gelatinosa are located predominantly on intrinsic an autoradiography study. J. Pharmacol. Exp. Ther. 247:757–764.

    Google Scholar 

  • Coderre, T. J., Katz, J., Vaccarino, A. L., and Melzack, R. (1993). Contribution of central neuroplasticity to pathological pain: Review of clinical and experimental evidence. Pain 52:259–285.

    Google Scholar 

  • Corradetti, R., Conte, G. L., Moroni, F., Passani, M. B., and Pepeu, G. (1984). Adenosine decreases aspartate and glutamate release from rat hippocampal slices. Eur. J. Pharmacol. 104:19–26.

    Google Scholar 

  • Geiger, J. D., Labella, F. S., and Nagy, J. I. (1984). Characterization and localization of adenosine receptors in rat spinal cord. J. Neurosci. 4:2303–2310.

    Google Scholar 

  • Jhamandas, K. H., Marsala, M., Ibuki, T., and Yaksh, T. L. (1996). Spinal amino acid release and precipitated withdrawal in rats chronically infused with spinalmorphine. J. Neurosci. 16:2758–2766.

    Google Scholar 

  • Liu, H., Mantyh, P. W., and Basbaum, A. I. (1997). NMDA-receptor regulation of substance P release from primary afferent nociceptors. Nature 386:721–724.

    Google Scholar 

  • Malmberg, A. B., and Yaksh, T. L. (1992). Hyperalgesia mediated by spinal glutamate or substance P receptor blocked by spinal cyclooxygenase inhibition. Science 257:1276–1279.

    Google Scholar 

  • Malmberg, A. B., and Yaksh, T. L. (1993a). Pharmacology of the spinal action of ketorolac, morphine, ST-91, U50488H, and L-PIA on the formalin test and an isobolographic analysis of the NSAID interaction. Anesthesiology 79:270–281.

    Google Scholar 

  • Malmberg, A. B., and Yaksh, T. L. (1993b). Spinal nitric oxide synthesis inhibition blocks NMDA-induced thermal hyperalgesia and produce antinociception in the formalin test in rats. Pain 54:291–300.

    Google Scholar 

  • Malmberg, A. B., and Yaksh, T. L. (1995). The effect of morphine on formalin-evoked behavior and spinal release of excitatory amino acids and prostaglandin E2 using microdialysis in conscious rats. Brit. J. Pharmacol. 114:1069–1075.

    Google Scholar 

  • Manzoni, O. J., Manabe, T., and Nicoll, R. A. (1994). Release of adenosine by activation of NMDA receptors in the hippocampus. Science 265:2098–2101.

    Google Scholar 

  • Marsala, M., Malmberg, A. B., and Yaksh, T. L. (1995). The spinal loop dialysis catheter: Characterization of use in the unanesthetized rat. J. Neurosci. Methods 62:43–53.

    Google Scholar 

  • Murray, C. W., Cowan, A., and Larson, A. A. (1991). Neurokinin and NMDA antagonists (but not a kainic acid antagonist) are antinociceptive in the mouse formalin model. Pain 44:179–185.

    Google Scholar 

  • Reeve, A. J., and Dickenson, A. H. (1995). The roles of spinal adenosine receptors in the control of acute and more persistent nociceptive responses of dorsal horn neurons in the anaesthetized rat. Brit. J. Pharmacol. 116:2221–2228.

    Google Scholar 

  • Sawynok, J., and Sweeney, M. I. (1989). The role of purines in nociception. Neuroscience 32:557–569.

    Google Scholar 

  • Sjolund, K. F., Sollevi, A., Segerdahl, M., and Lundeberg, T. (1997). Intrathecal adenosine analog administration reduces substance P in cerebrospinal fluid along with behavioral effects that suggest antinociception in rats. Anesth. Analg. 85:627–632.

    Google Scholar 

  • Skilling, S. R., Smullin, D. H., Beitz, A. J., and Larson, A. A. (1988). Extracellular amino acid concentrations in the dorsal spinal cord of freely moving rats following veratridine and nociceptive stimulation. J. Neurochem. 51:127–132.

    Google Scholar 

  • Sosnowski, M., Stevens, C., and Yaksh, T. L. (1989). Assessment of the role of A1/A2 adenosine receptors mediating the purine antinociception, motor and autonomic function in the rat spinal cord. J. Pharmacol. Exp. Ther. 250:915–922.

    Google Scholar 

  • Tjlsen, A., Berge, O. G., Hunskaar, S., Rosland, J. H., and Hole, K. (1992). The formalin test: An evaluation of the method. Pain 51:5–17.

    Google Scholar 

  • Yaksh, T. L. (1987). Spinal opiates: A review of their effect on spinal function with emphasis on pain processing. Acta Anaesth. Scand. 85:25–37.

    Google Scholar 

  • Yaksh, T. L., and Rudy, T. A. (1976). Chronic catherterization of the spinal subarachnoid space. Physiol. Behav. 17:1031–1036.

    Google Scholar 

  • Yamamoto, T., and Yaksh, T. L. (1992). Comparison of the antinociceptive effects of pre-and posttreatment with intrathecal morphine and MK801, an NMDA antagonist, on the formalin test in the rat. Anesthesiology 77:757–763.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yamamoto, S., Nakanishi, O., Matsui, T. et al. Intrathecal Adenosine A1 Receptor Agonist Attenuates Hyperalgesia Without Inhibiting Spinal Glutamate Release in the Rat. Cell Mol Neurobiol 23, 175–185 (2003). https://doi.org/10.1023/A:1022997805525

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1022997805525

Navigation