Decreased Pain Sensitivity of Capsaicin-Treated Rats Results from Decreased VR1 Expression

  • Lee, Soon-Youl (Department of Genomic Engineering, Genetic Informatics Center, GRRC Hankyong National University) ;
  • Hong, Young-Mi (The Sensory Research Center, National Creative Research Initiatives, College of Pharmacy, Seoul National University) ;
  • Oh, Uh-Taek (The Sensory Research Center, National Creative Research Initiatives, College of Pharmacy, Seoul National University)
  • Published : 2004.11.01

Abstract

We investigated the neurotoxic effects of capsaicin (CAP) on pain sensitivity and on the expression of capsaicin receptor, the vanilloid receptor (VR1), in rats. High-dose application of CAP has been known to degenerate a large fraction of the sensory neurons. Although the neurotoxic effects of CAP are well documented, the effects of CAP on the vanilloid receptor (VR1) are not yet known. In this paper, we investigated the effects of high-dose application of CAP on the expression of VR1 in rats. Thermal and mechanical pain sensitivity was reduced when neonatal rats were treated with a high dose of CAP. This reduction of pain sensitivity was significantly decreased after initiating carrageenan-induced inflammation. The expression of VR1 in dorsal root ganglia (DRG) isolated from the CAP-treated rats was reduced compared to that from the vehicle-treated rats. Therefore, we can conclude that the neurotoxic effect of CAP is related to the decrease of VR1 expression.

Keywords

References

  1. Arvidsson, J. and Ygge, J., A quantitative study of the effects of neonatal capsaicin treatment and of subsequent peripheral nerve transection in the adult rat. Brain Res., 397, 130-136 (1986) https://doi.org/10.1016/0006-8993(86)91376-4
  2. Buck, S. H. and Burks, T. F., The neuropharmacology of capsaicin: review of some recent observations. Pharmacol. Rev., 38, 179-226 (1986)
  3. Caterina, M. J., Schumacher, M. A., Tominaga, M., Rosen, T. A., Levine, J. D., and Julius, D., The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature, 389, 816-824 (1997) https://doi.org/10.1038/39807
  4. Caterina, M. J., Leffler, A., Malmberg, A. B., Martin, W. J., Trafton, J., Petersen-Zeitz, K. R., Koltzenburg, M., Basbaum, A. I., and Julius, D., Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science, 288, 306-313 (2000) https://doi.org/10.1126/science.288.5464.306
  5. Davis, J. B., Gray, J., Gunthorpe, M. J., Hatcher, J. P., Davey, P. T., Overend, P., Harries, M. H., Latcham, J., Clapham, C., Atkinson, K., Hughes, S. A., Rance, K., Grau, E., Harper, A. J., Pugh, P. L., Rogers, D. C., Bingham, S., Randall, A., and Sheardown, S. A., Vanilloid receptor-1 is essential for inflammatory thermal hyperalgesia. Nature, 405, 183-187 (2000) https://doi.org/10.1038/35012076
  6. Fitzgerald, M., Capsaicin and sensory $neurones-{\alpha}$ review. Pain, 15, 109-130 (1983) https://doi.org/10.1016/0304-3959(83)90012-X
  7. Gamse, R., Holzer, P., and Lembeck, F., Decrease of substance P in primary afferent neurones and impairment of neurogenic plasma extravasation by capsaicin. Br. J. Pharmacol., 68, 207-213 (1980) https://doi.org/10.1111/j.1476-5381.1980.tb10409.x
  8. Gamse, R., Capsaicin and nociception in the rat and mouse. Possible role of substance P. Naunyn Schmiedebergs. Arch. Pharmacol., 320, 205-216 (1982) https://doi.org/10.1007/BF00510129
  9. Gamse, R., Petsche, U., Lembeck, F., and Jancso, G., Capsaicin applied to peripheral nerve inhibits axoplasmic transport of substance P and somatostatin. Brain Res., 239, 447-462 (1982) https://doi.org/10.1016/0006-8993(82)90521-2
  10. Gao, X., Zhang, Y., and Wu, G., Effects of dopaminergic agents on carrageenan hyperalgesia in rats. Eur. J. Pharmacol., 406, 53-58 (2000) https://doi.org/10.1016/S0014-2999(00)00649-X
  11. Hammond, D. L. and Ruda, M. A., Developmental alterations in thermal nociceptive threshold and the distribution of immuno-reactive calcitonin gene-related peptide and substance P after neonatal administration of capsaicin in the rat. Neurasci. Lett., 97, 57-62 (1989) https://doi.org/10.1016/0304-3940(89)90139-0
  12. Hammond, D. L. and Ruda, M. A., Developmental alterations in nociceptive threshold, immunoreactive calcitonin generelated peptide and substance P, and fluoride-resistant acid phosphatase in neonatally capsaicin-treated rats. J. Camp. Neurol.,312, 436-450 (1991) https://doi.org/10.1002/cne.903120310
  13. Hylden, J. L., Noguchi, K., and Ruda, M. A., Neonatal capsaicin treatment attenuates spinal Fos activation and dynorphin gene expression following peripheral tissue inflammation and hyperalgesia. J. Neurasci., 12, 1716-1725 (1992)
  14. Holzer, P., Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons. Pharmacol. Rev., 43, 143-201 (1991)
  15. Hwang, S. W., Cho, H., Kwak, J., Lee, S. Y., Kang, C. J., Jung, J., Cho, S., Min, K. H., Suh, Y. G., Kim, D., and Oh, U., Direct activation of capsaicin receptors by products of lipoxy-genases: endogenous capsaicin-like substances. Proc. Natl. Acad. Sci. U.S.A., 97, 6155-6160 (2000) https://doi.org/10.1073/pnas.97.11.6155
  16. Jancso, G., Kiraly, E., and Jancso-Gabor, A., Pharmacologically induced selective degeneration of chemosensitive primary sensory neurones. Nature, 270, 741-743 (1977) https://doi.org/10.1038/270741a0
  17. Kwan, C. L., Hu, J. W., and Sessle, B. J., Neuroplastic effects of neonatal capsaicin on neurons in adult rat trigeminal nucleus principalis and subnucleus oralis. J. Neurophysiol., 75, 298-310 (1996) https://doi.org/10.1152/jn.1996.75.1.298
  18. Kwak, J. Y., Jung, J. Y., Hwang, S. W., Lee, W. T., and Oh U., A capsaicin-receptor antagonist, capsazepine, reduces inflammation-induced hyperalgesic responses in the rat: evidence for an endogenous capsaicin-like substance. Neuroscience, 86, 619-626 (1998) https://doi.org/10.1016/S0306-4522(98)00012-8
  19. Laszlo, U., Elizabath, A. C., Moh, P., Sadhana, P., and Naureen, C., In vivo pharmacology of SDZ 249-665, a novel, nonpungent capsaicin analogue. Pain, 89, 65-74 (2000) https://doi.org/10.1016/S0304-3959(00)00349-3
  20. McDougal, D. B. Jr, McDougal, S. H., and Johnson, E. M. Jr., Effect of capsaicin upon fluoride sensitive acid phosphatases in selected ganglia and spinal cord and upon neuronal size and number in dorsal root ganglion. Brain Res., 331, 63-70 (1985) https://doi.org/10.1016/0006-8993(85)90715-2
  21. Oh, U., Hwang, S. W., and Kim, D., Capsaicin activates a nonselective cation channel in cultured neonatal rat dorsal root ganglion neurons. J. Neurosci., 16, 1659-1667 (1996)
  22. Ren, K., Williams, G. M., Ruda, M. A., and Dubner, R., Inflammation and hyperalgesia in rats neonatally treated with capsaicin: effects on two classes of nociceptive neurons in the superficial dorsal horn. Pain, 59, 287-300 (1994) https://doi.org/10.1016/0304-3959(94)90082-5
  23. Shin, J., Cho, H., Hwang, S. W., Jung, J., Shin, C. Y., Lee, S. Y., Kim, S. H., Lee, M. G., Choi, Y. H., Kim, J., Haber, N. A., Reichling, D. B., Khasar, S., Levine, J. D., and Oh, U., Bradykinin-12-lipoxygenase-VR1 signaling pathway for inflammatory hyperalgesia. Proc. Natl. Acad. Sci. U.S.A., 99, 10150-10155 (2002) https://doi.org/10.1073/pnas.152002699
  24. Smart, D., Gunthorpe, M. J., Jerman, J. C., Nasir, S., Gray, J., Muir, A. I., Chambers, J. K., Randall, A. D., and Davis, J. B., The endogenous lipid anandamide is a full agonist at the human vanilloid receptor (hVR1). Br. J. Pharmacol., 129, 227-230 (2000) https://doi.org/10.1038/sj.bjp.0703050
  25. Zygmunt, P. M., Peterson, J., Andersson, D. A., Chuang, H., Sorgard, M., Di Marzo, V., Julius, D., and Hogestatt, E. D., Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature, 400, 452-457 (1999) https://doi.org/10.1038/22761