The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Involvement of NMDA Receptor and L-type Calcium Channel in the Excitatory Action of Morphine

  • Koo, Bon-Seop (Department of Orthopedics, Kangbuk Samsung Hospital, Sungkyunkwan University College of Medicine) ;
  • Shin, Hong-Kee (Departments of Physiology, College of Medicine, Hanyang University) ;
  • Kang, Suk-Han (Departments of Physiology, College of Medicine, Hanyang University) ;
  • Jun, Jong-Hun (Departments of Anesthesiology, College of Medicine, Hanyang University)
  • Published : 2002.10.21
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Abstract

We studied the excitatory action of morphine on the responses of dorsal horn neuron to iontophoretic application of excitatory amino acid and C-fiber stimulation by using the in vivo electrophysiological technique in the rat. In 137 of the 232 wide dynamic range (WDR) neurons tested, iontophoretic application of morphine enhanced the WDR neuron responses to N-methyl-D-aspartate (NMDA), kainate, and graded electrical stimulation of C-fibers. Morphine did not have any excitatory effects on the responses of low threshold cells. Morphine-induced excitatory effect at low ejection current was naloxone-reversible and reversed to an inhibitory action at high ejection current. NMDA receptor, calcium channel and intracellular $Ca^{2+}$ antagonists strongly antagonized the morphine-induced excitatory effect. These results suggest that changes in intracellular ionic concentration, especially $Ca^{2+},$ play an important role in the induction of excitatory effect of morphine in the rat dorsal horn neurons.

Keywords

References

  1. Attali B, Saya D, Nah S-Y, Vogel Z. $\kappa$-Opiate agonists inhibit Ca$^2+$ influx in rat spinal cord-dorsal root ganglion cocultures. J Biol Chem 264:347-353, 1989
  2. Belcher G, Ryall RW. Differential excitatory and inhibitory effects of opiates on non-nociceptive and nociceptive neurones in the spinal cord of the cat. Brain Res 145: 303－314, 1978 https://doi.org/10.1016/0006-8993(78)90864-8
  3. Chen G-G, Chalazonitis A, Shen K-F, Crain SM. Inhibitor of cyclic AMP-dependent protein kinase blocks opioid-induced prolongation of the action potential of mouse sensory ganglion neurons in dissociated cell cultures. Brain Res 462: 372－377, 1988 https://doi.org/10.1016/0006-8993(88)90568-9
  4. Coderre TJ. Contribution of protein kinase C to central sensitization and persistent pain following tissue jnjury. Neurosci Lett 140: 81－184, 1992 https://doi.org/10.1016/0304-3940(92)90687-3
  5. Crain SM, Shen K-F, Chalazonitis A. Opioids excite rather than inhibit sensory neurons after chronic opioid exposure of spinal cord-ganglion cultures. Brain Res 455: 99－109, 1988 https://doi.org/10.1016/0006-8993(88)90118-7
  6. Crain SM, Shen K-F. Enhanced analgesic potency and reduced tolerance of morphine in 129/SvEv mice: evidence for a deficiency in GM1 ganglioside-regulated excitatory opioid receptor functions. Brain Res 856: 227－235, 2000 https://doi.org/10.1016/S0006-8993(99)02446-4
  7. Crain SM, Shen K-F. Acute thermal hyperalgesia elicited by low-dose morphine in normal mice is blocked by ultra-low-dose naltrexone, unmasking potent opioid analgesia. Brain Res 888: 75－82, 2001 https://doi.org/10.1016/S0006-8993(00)03010-9
  8. Davies J, Dray A. Effects of enkephalin and morphine on Renshaw cells in feline spinal cord. Nature 262: 603－604, 1976 https://doi.org/10.1038/262603a0
  9. Einspahr FJ, Piercey MF. Morphine depresses dorsal horn neuron responses to controlled noxious and non-noxious cutaneous stimulation. J Pharmacol Exp Ther 213: 456－461, 1980
  10. Jin W, Lee NM, Loh HH, Thayer SA. Dual excitatory and inhibitory effects of opioids on intracellular calcium in neuroblastoma X glioma hybrid NG 108-15 cells. Mol Pharmacol 42: 1083－1089, 1992
  11. Jin W, Lee NM, Loh HH, Thayer SA. Opioids mobilize calcium from inositol 1,4,5-trisphosphate-sensitive stores in NG 108-15 cells. J Neurosci 14: 1920－1929, 1994
  12. Kayser V, Besson JM, Guilbaud G. 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, 1987 https://doi.org/10.1016/0006-8993(87)91338-2
  13. Knox RJ, Dickenson AH. Effects of selective and non-selective $\kappa$- opioid receptor agonists on cutaneous C-fiber-evoked responses of rat dorsal horn neurons. Brain Res 415: 21-49, 1987 https://doi.org/10.1016/0006-8993(87)90265-4
  14. Le Bars D, Rivot JP, Guilbaud G, Menetrey D, Besson JM. The depressive effects of morphine on the C fibre response of dorsal horn neurones in the spinal rat pretreated or not by pCPA. Brain Res 176: 337－353, 1979 https://doi.org/10.1016/0006-8993(79)90988-0
  15. Lembeck F, Donnerer J. Opioid control of the function of primary afferent substance P fibres. Europ J Pharmacol 114: 241－246, 1985 https://doi.org/10.1016/0014-2999(85)90365-6
  16. Lin Y, Carpenter DO. Direct excitatory opiate effects mediated by non-synaptic actions on rat medial vestibular neurons. Europ J Pharmacol 262: 90－106, 1994
  17. Neal MJ, Paterson SJ, Cunningham JR. Enhancement of retinal acetylcholine release by DAMGO: possibly a direct opioid receptor-mediated excitatory effect. Brit J Pharmacol 113: 789－ 794, 1994 https://doi.org/10.1111/j.1476-5381.1994.tb17062.x
  18. North RA, Williams JT, Surprenant A, Christie MJ. $\mu$ - and $\delta$- receptors belong to a family of receptors that are coupled to potassium channels. Proc Natl Acad Sci USA 84: 5489－5491, 1987
  19. Rasmussen K, Jacobs BL. Locus coeruleus unit activity in freely moving cats is increased following systemic morphine administration. Brain Res 344: 240－248, 1985 https://doi.org/10.1016/0006-8993(85)90801-7
  20. Satoh M, Zieglgänsberger W, Fries W, Herz A. Opiate agonistantagonist interaction at cortical neurones of naive and tolerant/ dependent rats. Brain Res 82: 378－382, 1974 https://doi.org/10.1016/0006-8993(74)90624-6
  21. Shen K-F, Crain SM. Dual opioid modulation of the action potential duration of mouse dorsal root ganglion neurons in culture. Brain Res 491: 227－242, 1989 https://doi.org/10.1016/0006-8993(89)90059-0
  22. Shen K-F, Crain SM. Cholera toxin-A subunit blocks opioid excitatory effects on sensory neuron action potentials indicating mediation by Gs-linked opioid receptors. Brain Res 525: 225－ 231, 1990 https://doi.org/10.1016/0006-8993(90)90868-C
  23. Shen K-F, Crain SM. Chronic selective activation of excitatory opioid receptor functions in sensory neurons results in opioid dependence without tolerance. Brain Res 597: 74－83, 1992 https://doi.org/10.1016/0006-8993(92)91507-B
  24. Smart D, Lambert DG. $\delta$-opioids stimulate inositol 1,4,5-trisphosphate formation and so mobilize Ca$^2+$ from intracellular stores in undifferentiated NG 108-15 cells. J Neurochem 66: 1462－1467, 1996 https://doi.org/10.1046/j.1471-4159.1996.66041462.x
  25. Suarez-Roca H, Maixner W. Activation of kappa opioid receptors by U50488H and morphine enhances the release of substance P from rat trigeminal nucleus slices. J Pharmacol Exp Ther 264: 648－653, 1993
  26. Taiwo YO, Basbaum AI, Perry F, Levine JD. Paradoxical analgesia produced by low doses of the opiate-antagonist naloxone is mediated by interaction at site with characteristics of the delta opioid receptor. J Pharmacol Exp Ther 249: 97－100, 1989
  27. Werz MA, Macdonald RL. Opioid peptides with differential affinity for mu and delta receptors decrease sensory neuron calcium- dependent action potentials. J Pharmacol Exp Ther 227: 394－402, 1983
  28. Willcockson WS, Kim J, Shin HK, Chung JM, Willis WD. Actions of opioids on primate spinothalamic tract neurons. J Neurosci 6: 2509－2520, 1986
  29. Williams JT, Egan TM, North RA. Enkephalin opens potassium channels on mammalian central neurones. Nature 299: 74－77, 1982 https://doi.org/10.1038/299074a0
  30. Wu G, Fan SF, Lu Z-H, Ledeen RW, Crain SM. Chronic opioid treatment of neuroblastoma x dorsal root ganglion neuron hybrid F11 cells results in elevated GM1 ganglioside and cyclic adenosine monophosphate levels and onset of naloxone-evoked decreases in membrane K$^+$ currents. J Neurosci Res 42: 493－503,1995 https://doi.org/10.1002/jnr.490420408
  31. Yaksh TL, Jessell TM, Gamse R, Mudge AW, Leeman SE. Intrathecal morphine inhibits substance P release from mammalian spinal cord in vivo. Nature 286: 155－157, 1980 https://doi.org/10.1038/286155a0
  32. Yaksh TL, Rudy TA. Studies on the direct spinal action of narcotics in the production of analgesia in the rat. J Pharmacol Exp Ther 202: 411－428, 1977
  33. Zieglgänsberger W, French ED, Siggins GR, Bloom FE. Opioid peptides may excite hippocampal pyramidal neurons by inhibiting adjacent inhibitory interneurones. Science 205: 415－417, 1979 https://doi.org/10.1126/science.451610