Morphine-induced Modulation of Nociceptive Spinal Dorsal Horn Neuronal Activities after Formalin-induced Inflammatory Pain

  • Park, Joo-Min (Department of Physiology, Seoul National University College of Medicine) ;
  • Li, Kang-Wu (Department of Physiology, Seoul National University College of Medicine) ;
  • Jung, Sung-Jin (Department of Physiology, Kangwon National University College of Medicine) ;
  • Kim, Jun (Department of Physiology, Seoul National University College of Medicine) ;
  • Kim, Sang-Jeong (Department of Physiology,Xenotransplantation Research Center, Seoul National University College of Medicine)
  • 발행 : 2005.04.21

초록

In this study, we examined the morphine-induced modulation of the nociceptive spinal dorsal horn neuronal activities before and after formalin-induced inflammatory pain. Intradermal injection of formalin induced time-dependent changes in the spontaneous activity of nociceptive dorsal horn neurons. In naive cats before the injection of formalin, iontophoretically applied morphine attenuated the naturally and electrically evoked neuronal responses of dorsal horn neurons. However, neuronal responses after the formalin-induced inflammation were significantly increased by morphine. Bicuculline, $GABA_A$ antagonist, increased the naturally and electrically evoked neuronal responses of dorsal horn neurons. This increase in neuronal responses due to bicuculline after the formalin-induced inflammation was larger than that in the naive state, suggesting that basal $GABA_A$ tone increased after the formalin injection. Muscimol, $GABA_A$ agonist, reduced the neuronal responses before the treatment with formalin, but not after formalin treatment, again indicating an increase in the GABAergic basal tone after the formalin injection which saturated the neuronal responses to GABA agonist. Morphine-induced increase in the spinal nociceptive responses after formalin treatment was inhibited by co-application of muscimol. These data suggest that formalin-induced inflammation increases $GABA_A$ basal tone and the inhibition of this augmented $GABA_A$ basal tone by morphine results in a paradoxical morphineinduced increase in the spinal nociceptive neuronal responses after the formalin-induced inflammation.

키워드

참고문헌

  1. Akaishi T, Saito H, Ito Y, Ishige K, Ikegaya Y. Morphine augments excitatory synaptic transmission in the dentate gyrus through GABAergic disinhibition. Neurosci Res 38: 357 - 363, 2000 https://doi.org/10.1016/S0168-0102(00)00177-2
  2. Besson JM, Chaouch A. Peripheral and spinal mechanism of nociception. Physiol Rev 67: 67 -185, 1987 https://doi.org/10.1152/physrev.1987.67.1.67
  3. Belcher G, Ryall RW. Differential excitatory and inhibitory effects of opiates on non-nociceptive and nociceptive neurons in the spinal cord of the cat. Brain Res 145: 303-314, 1978 Campbell IN, Meyer RA, LaMotte RH. Sensitization of myelinated nociceptive afferents that innervate monkey hand. J Neurophysiol 42: 1669 -1679, 1979
  4. Campbell IN, Meyer RA, LaMotte RH. Sensitization of myelinated nociceptive afferents that innervate monkey hand. J Neurophysiol 42: 1669 -1679, 1979 https://doi.org/10.1152/jn.1979.42.6.1669
  5. Carlton SM, Westlund KN, Zhang D, Willis WD. GABA- immunoreactive terminals synapse on primate spinothalamic tract cells. J Comp Neurol 322: 528-537, 1992 https://doi.org/10.1002/cne.903220407
  6. Castro-Lopes JM, Tavares I, Tolle TR, Coimbra A. Carrageenaninduced inflammation of the hind foot provokes a rise of GABAimmunoreactive cells in the rat spinal cord that is prevented by peripheral neurectomy or neonatal capsaicin treatment. Pain 56: 193 - 201, 1994 https://doi.org/10.1016/0304-3959(94)90094-9
  7. Castro-Lopes JM, Malcangio M, Pan BH, Bowery NG. Complex changes of GABAA and GABAs receptor binding in the spinal cord dorsal horn following peripheral inflammation or neurectomy. Brain Res 679: 289 - 297, 1995 https://doi.org/10.1016/0006-8993(95)00262-O
  8. Celerier E, Laulin J, Larcher A, Le Moal M, Simonnet G. Evidence for opiate-activated NMDA processes masking opiate analgesia in rats. Brain Res 847: 18-25, 1999 https://doi.org/10.1016/S0006-8993(99)01998-8
  9. Chung JM, Surmeier DJ, Lee KH, Sorkin LS, Honda CN, Tsong Y, Willis WD. Classification of primate spinothalamic and somatosensory thalamic neurons based on cluster analysis. J Neurophysiol 56: 308 - 327, 1986 https://doi.org/10.1152/jn.1986.56.2.308
  10. Dostrovsky JO, Pomeranz B. Interaction of iontophoretically applied morphine with response of interneurons in cat spinal cord. Exp Neurol 52: 325 - 338, 1976 https://doi.org/10.1016/0014-4886(76)90175-8
  11. Dickenson AH, Sullivan AF. Subcutaneous formalin-induced activity of dorsal horn neurons in the rat: different response to an intrathecal opiate administered pre or post formalin. Pain 30: 349 - 360, 1987 https://doi.org/10.1016/0304-3959(87)90023-6
  12. Hammond DL, Wang H, Nakashima N, Basbaum Al. Differential effects of intrathecally administered delta and mu opioid receptor agonists on formalin-evoked nociception and on the expression of Fos-like immunoreactivity in the spinal cord of the rat. J Pharmacol Exp Ther 284: 378-387, 1998
  13. Hylden JLK, Nahin RL, Traub RJ, Dubner R. Effects of spinal kappa-opioid receptor agonists on the responsiveness of nociceptive superficial dorsal horn neurons. Pain 44: 187 -193, 1991 https://doi.org/10.1016/0304-3959(91)90136-L
  14. Inturrisi CE. Clinical pharmacology of opioids for pain. Clin J Pain 18: S3-S13, 2002 https://doi.org/10.1097/00002508-200207001-00002
  15. Jones SL, Sedivec MJ, Light AR. Effects of iontophoresed opioids on physiologically characterized laminae I and II dorsal horn neurons in the cat spinal cord. Brain Res 532: 160-174, 1990 https://doi.org/10.1016/0006-8993(90)91756-7
  16. Kalyuzhny AE, Wessendorf MW. Relationship of mu- and deltaopioid receptors to GABAergic neurons in the central nervous system, including antinociceptive brainstem circuits. J Comp Neurol 392: 528- 547, 1998 https://doi.org/10.1002/(SICI)1096-9861(19980323)392:4<528::AID-CNE9>3.0.CO;2-2
  17. Kayser V, Guilbaud G. Differential effects of various doses of morphine and naloxone on two nociceptive test thresholds in arthritic and normal rats. Pain 41: 353 - 363, 1990 https://doi.org/10.1016/0304-3959(90)90012-3
  18. Kayser V, Chen YL, Guilbaud G. Behavioural evidence for a peripheral component in the enhanced antinociceptive effect of a low dose of systemic morphine in carrageenan-induced hyperalgesic rats. Brain Res 560: 237 - 244, 1991 https://doi.org/10.1016/0006-8993(91)91238-V
  19. Kemp T, Spike RC, Watt C, Todd AJ. The mu-opioid receptor (MOR1) is mainly restricted to neurons that do not contain GABA or glycine in the superficial dorsal horn of the rat spinal cord. Neurosci 74: 1231-1238, 1996
  20. Knox RJ, Dickenson AH. Effects of selective and non-selective -opioid receptor agonists on cutaneous C-fibre-evoked responses of rat dorsal horn neurons. Brain Res 415: 21- 29, 1987 https://doi.org/10.1016/0006-8993(87)90265-4
  21. LaMotte RH, Thalhammer JG, Robinson CJ. Peripheral neural correlates of magnitude of cutaneous pain and hyperalgesia: a comparison of neural events in monkey with sensory judgments in human. J Neurophysiol 50: 126, 1983
  22. Lin Q, Peng YB, Willis WD. Role of GABA receptor subtype in inhibition of primate spinothalamic tract neurons: Difference between spinal and periaqueductal gray inhibition. J Neurophysiol 76: 1005 -1014, 1996 https://doi.org/10.1152/jn.1996.76.2.1005
  23. Lin Y, Carpenter DO. Direct excitatory opiate effects mediated by non-synaptic actions on rat medial vestibular neurons. Eur J Pharmacol 262: 99 -106, 1994 https://doi.org/10.1016/0014-2999(94)90032-9
  24. Mascias P, Scheede M, Bloms-Funke P, Chizh B. Modulation of spinal nociception by GluR5 kainate receptor ligands in acute and hyperalgesic states and the role of gabaergic mechanisms. Neuropharmacology 42: 327 - 339, 2002
  25. Magnuson DS, Dickenson AH. Lamina-specific effects of morphine and naloxone in dorsal horn of rat spinal cord in vitro. J Neurophysiol 66: 1941-1950, 1991 https://doi.org/10.1152/jn.1991.66.6.1941
  26. Melzack R, Wall PD. Pain mechanism, a new theory. Science 150: 971- 979, 1965 https://doi.org/10.1126/science.150.3699.971
  27. Moran TD, Smith PA. Morphine-3beta-D-glucuronide suppresses inhibitory synaptic transmission in rat substantia gelatinosa. J Pharmacol Exp Ther 302: 568 - 576, 2002 https://doi.org/10.1124/jpet.102.035626
  28. Neil A, Kayser V, Gacel G, Besson JM, Guilbaud G. Opioid receptor types and antinociceptive activity in chronic inflammation: both kappa- and mu-opiate agonistic effects are enhanced in arthritic rats. Eur J Pharmacol 130: 203 - 208, 1986 https://doi.org/10.1016/0014-2999(86)90269-4
  29. Neumaier JF, Mailheau S, Chavkin C. Opioid receptor-mediated responses in the dentate gyrus and CAl region of the rat hippocampus. J Pharmacol Exp Ther 244: 564 - 570, 1988
  30. North RA. Opioid receptor types and membrane ion channel. Trends Neurosci 9: 114-117, 1986 https://doi.org/10.1016/0166-2236(86)90038-X
  31. Piercey MF, Einspahr FJ, Dobry PJ, Schroeder LA, Hollister RP. Morphine does not antagonize the substance P mediated excitation of dorsal horn neurons. Brain Res 186: 421- 434, 1980 https://doi.org/10.1016/0006-8993(80)90986-5
  32. Reeve AJ, Dickenson AH, Kerr NC. Spinal effects of bicuculline: Modulation of an allodynia-like state by an A'l-receptor agonist, morphine, and an NMDA-receptor antagonist. J Neurophysiol 79: 1494-1507, 1988
  33. Rivat C, Laulin JP, Corcuff JB, Celerier E, Pain L, Simonnet G. Fentanyl enhancement of carrageenan-induced long-lasting hyperalgesia in rats: prevention by the N-methyl-D-aspartate receptor antagonist ketamine. Anesthesiology 96: 381- 391, 2002 https://doi.org/10.1097/00000542-200202000-00025
  34. 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 Pharmacal Exp Ther 264: 648-653, 1993
  35. Suarez-Roca H, Maixner W. Morphine produces a biphasic modulation of substance P release from cultured dorsal root ganglion neuroits. Neurosci Lett 194: 41- 44, 1995 https://doi.org/10.1016/0304-3940(95)11721-8
  36. Tan-No K, Esashi A, Nakagawasai 0, Niijima F, Tadano T, Sakurada C, Sakurada T, Bakalkin G, Terenius L, Kisara K. Intrathecally administered big dynorphin, a prodynorphinderived peptide, produces nociceptive behavior through an Nmethyl-D-aspartate receptor mechanism. Brain Res 952: 7 -14, 2002 https://doi.org/10.1016/S0006-8993(02)03180-3
  37. Tjolsen A, Berge O-G, Hunskaar S, Rosland AH, Hole K. The formalin test: an evaluation of the method. Pain 51: 5 -17, 1992 https://doi.org/10.1016/0304-3959(92)90003-T
  38. Trevino DL, Coulter JD, Willis WD. Location of cells of origin of spinothalamic tract in lumbar enlargement of the monkey. J Neurophysiol 36: 750-761, 1973 https://doi.org/10.1152/jn.1973.36.4.750
  39. Zieglgansberger W, French ED, Siggins GR, Bloom FE. Opioid peptides may excite hippocampal pyramidal neurons by inhibiting adjacent inhibitory interneurons. Science 205: 415-417, 1979 https://doi.org/10.1126/science.451610