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Multiphasic Morphine Modulation of Substance P Release from Capsaicin-Sensitive Primary Afferent Fibers

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Abstract

Morphine produces a multiphasic modulation of K+-evoked substance P release from trigeminal slices and dorsal root ganglion neurons in culture. We now found that the C-fiber stimulant, capsaicin (1 μM), evoked release of substance P that was inhibited, enhanced and inhibited by 0.1 nM, 1 μM, and 10 μM morphine, respectively. This morphine's multiphasic effect was blocked by naloxone (100 nM). Neonatal treatment with capsaicin produced thermal hypoalgesia and abolished the multiphasic effect of morphine on substance P release evoked by 50 mM K+. These findings suggest that the multiphasic modulation of substance P release by morphine is dependent on C-type afferents and may be of relevance to nociception.

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REFERENCES

  1. Bossut, D., Frank, H., and Mayer, D. J. 1988. Is substance P a primary afferent neurotransmitter for nociceptive input? II. Spinalization does not reduce and intrathecal morphine potentiates behavioral responses to substance P, Brain Res., 455:232–239.

    Google Scholar 

  2. Yaksh, T. L. 1986. The central pharmacology of primary afferents with emphasis on the disposition and role of primary afferent substance P. Pages 165–96, in Yaksh TL, Functional organization of spinal afferent processing, Plenum Press, New York.

    Google Scholar 

  3. Jessell, T. M., and Iversen, L. L. 1977. Opiate analgesics inhibit substance P release from rat trigeminal nucleus, Nature, 268:549–551.

    Google Scholar 

  4. Chang, H. M., Berde, C. B., Holz, G. G., Steward, G. F., and Kream, R. M. 1989. Sufentanil, morphine, met-enkephalin, and κ-agonist (U-50,488H) inhibit substance P release from primary sensory neurons: a model for presynaptic spinal opioid actions, Anesthesiology, 70:672–677.

    Google Scholar 

  5. Go, V. L. W., and Yaksh, T. L. 1987. Release of substance P from cat spinal cord, J. Physiol. (Lond.), 391:141–167.

    Google Scholar 

  6. Pang, I.-H., and Vasko, M. R. 1986. Morphine and norepinephrine but not 5-hydroxytryptamine and gamma-aminobutyric acid inhibit the potassium-stimulated release of substance P from rat spinal cord slices, Brain Res., 376:268–279.

    Google Scholar 

  7. Suarez-Roca, H., Abdullah, L., Zuniga, J., Madison, S., and Maixner, W. 1992. Multiphasic effect of morphine on the release of substance P from the rat trigeminal nucleus caudalis, Brain Res., 579:187–194.

    Google Scholar 

  8. Suarez-Roca, H., and Maixner, W. 1992. Morphine produces a multiphasic effect on substance P release from trigeminal nucleus caudalis slices by activating different opioid receptor subtypes, Brain Res., 579:195–203.

    Google Scholar 

  9. Suarez-Roca, H., and Maixner, W. 1992. Delta-opioid receptor activation by [D-Pen2,D-Pen5]enkephalin and morphine inhibits substance P release from trigeminal nucleus slices, Eur. J. Pharmacol., 229:1–7.

    Google Scholar 

  10. Hokfelt, T., Kellerth, J. O., Nillson, G., and Pernow, B. 1975. Experimental immunohistochemical studies on the localization and distribution of substance P in cat primary sensory neurons, Brain Res., 100:235–252.

    Google Scholar 

  11. Nagy, J. I., Iversen, L. L., Goedert, M., Chapman, D., and Hunt, S. P. 1983. Dose-dependent effects of capsaicin on primary sensory neurons in the neonatal rat, J. Neurosci., 3:399–406.

    Google Scholar 

  12. Bevan, S., and Szolcsanyl, J. 1992. Sensory neurons-specific actions of capsaicin: mechanisms and applications, TIPS, 11:330–333.

    Google Scholar 

  13. Glass, J., Chan, W. C., and Gintzler, A. R. 1986. Direct analysis of the release of methionine-Enkephalin from guinea pig myenteric plexus: Modulation by endogenous opioids and exogenous morphine, J. Pharm. Exp. Ther., 239:742–747.

    Google Scholar 

  14. Glazer, E. J., and Basbaum, A. I. 1981. Immunohistochemical localization of Leu-enkephalin in the spinal cord of rat: Enkephalin-containing marginal neurons and pain modulation, J. Comp. Neurol., 196:377–389.

    Google Scholar 

  15. Faris, P. L., Komisaruk, B. R., Watkins, L. R., and Mayer, D. J. 1983. Evidence for the neuropeptide cholecystokinin as an antagonist of opiate analgesia, Science, 219:310–312.

    Google Scholar 

  16. Tang, J., Chou, J., Ladarola, M., Yang, H. Y., and Costa, E. 1984. Proglumide prevents and curtails acute tolerance to morphine in rats, Neuropharmacology, 23:715–718.

    Google Scholar 

  17. Neil, A. 1984. Affinities of some common opioid analgesics towards four binding sites in mouse brain, Naunyn-Schmiedeberg's Arch. Pharmacol., 238:24–29.

    Google Scholar 

  18. Besse, D., Lombard, M. C., Zajac, J. M., Roques, B. P., and Besson, J. M. 1990. Pre-and postsynaptic distribution of mu, delta and kappa receptors in the superficial layers of the cervical dorsal horn of the rat spinal cord, Brain Res., 521:15–22.

    Google Scholar 

  19. Shen, K.-F., and Crain, S. M. 1989. Dynorphin prolongs the action potential duration of mouse sensory ganglion neurons by decreasing a potassium conductance whereas the specific kappa opioid, U-50,488H does so by increasing a calcium conductance, Prog. Clin. Biol. Res., 328:343–346.

    Google Scholar 

  20. Suarez-Roca, H., and Maixner, W. 1995. Morphine produces a bidirectional modulation of substance P release from cultured dorsal root ganglion neurons, Neurosci. Lett., 194:1–4.

    Google Scholar 

  21. Kayser, V., Bessar, J. M., and Guilbaud, G. 1987. Paradoxical hyperalgesic effect of exceedingly low doses of systemic morphine in an animal model of persistent pain (Freund's adjuvant-induced arthritic rats), Brain Res., 414:155–157.

    Google Scholar 

  22. Woolf, C. J. 1981. Intrathecal high dose morphine produces hyperalgesia in the rat, Brain Res., 209:491–495.

    Google Scholar 

  23. Jancso, G., and Jancso-Gabor, A. 1980. Effect of capsaicin on morphine analgesia. Possible involvement of hypothalamic structures. Naunyn Schmiedebrgs Arch. Pharmacol., 311:285–288.

    Google Scholar 

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Cano, G., Arcaya, J.L., Gómez, G. et al. Multiphasic Morphine Modulation of Substance P Release from Capsaicin-Sensitive Primary Afferent Fibers. Neurochem Res 24, 1203–1207 (1999). https://doi.org/10.1023/A:1020963120333

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