International Journal of Oral Biology

The Korean Academy of Oral Biology (대한구강생물학회)
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Involvement of Crosstalk Between cAMP and cGMP in Synaptic Plasticity in the Substantia Gelatinosa Neurons

  • Kim, Tae-Hyung (Department of Neurobiology and Physiology, School of Dentistry, Seoul National University) ;
  • Chung, Ge-Hoon (Department of Neurobiology and Physiology, School of Dentistry, Seoul National University) ;
  • Park, Seok-Beom (Department of Physiology, School of Medicine, Kangwon National University) ;
  • Chey, Won-Young (Department of Physiology, School of Medicine, Kangwon National University) ;
  • Jun, Sung-Jun (Department of Physiology, School of Medicine, Hanyang University) ;
  • Kim, Joong-Soo (Department of Neurobiology and Physiology, School of Dentistry, Seoul National University) ;
  • Oh, Seog-Bae (Department of Neurobiology and Physiology, School of Dentistry, Seoul National University)
  • Received : 2011.04.13
  • Accepted : 2011.04.29
  • Published : 2011.06.30
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Abstract

Substantia gelatinosa (SG) neurons receive synaptic inputs from primary afferent $A{\delta}$- and C-fibers, where nociceptive information is integrated and modulated by numerous neurotransmitters or neuromodulators. A number of studies were dedicated to the molecular mechanism underlying the modulation of excitability or synaptic plasticity in SG neurons and revealed that second messengers, such as cAMP and cGMP, play an important role. Recently, cAMP and cGMP were shown to downregulate each other in heart muscle cells. However, involvement of the crosstalk between cAMP and cGMP in neurons is yet to be addressed. Therefore, we investigated whether interaction between cAMP and cGMP modulates synaptic plasticity in SG neurons using slice patchclamp recording from rats. Synaptic activity was measured by excitatory post-synaptic currents (EPSCs) elicited by stimulation onto dorsal root entry zone. Application of 1 mM of 8-bromoadenosine 3,5-cyclic monophosphate (8-Br-cAMP) or 8-bromoguanosine 3,5-cyclic monophosphate (8-Br-cGMP) for 15 minutes increased EPSCs, which were maintained for 30 minutes. However, simultaneous application of 8-BrcAMP and 8-Br-cGMP failed to increase EPSCs, which suggested antagonistic cross-talk between two second messengers. Application of 3-isobutyl-1-methylxanthine (IBMX) that prevents degradation of cAMP and cGMP by blocking phosphodiesterase (PDE) increased EPSCs. Co-application of cAMP/cGMP along with IBMX induced additional increase in EPSCs. These results suggest that second messengers, cAMP and cGMP, might contribute to development of chronic pain through the mutual regulation of the signal transduction.

Keywords

References

  1. Bliss TV, Collingridge GL. A synaptic model of memory: longterm potentiation in the hippocampus. Nature. 1993;361 (6407):31-9. https://doi.org/10.1038/361031a0
  2. Bliss TV, Lomo T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol. 1973; 232(2):331-56.
  3. Campbell JN, Meyer RA, LaMotte RH. Sensitization of myelinated nociceptive afferents that innervate monkey hand. J Neurophysiol. 1979;42:1669-1679. https://doi.org/10.1152/jn.1979.42.6.1669
  4. Cerne R, Jiang M, Randic M. Cyclic adenosine 3'5'- monophosphate potentiates excitatory amino acid and synaptic responses of rat spinal dorsal horn neurons. Brain Res. 1992;596:111-123. https://doi.org/10.1016/0006-8993(92)91538-P
  5. Edwards FA, Konnerth A, Sakmann B, Takahashi T. A thin slice preparation for patch clamp recordings from neurons of the mammalian central nervous system. Pflugers Arch. 1989;414 (5):600-612. https://doi.org/10.1007/BF00580998
  6. Feil R, Hofmann F, Kleppisch T. Function of cGMP-dependent protein kinases in the nervous system. Rev Neurosci. 2005; 16(1):23-41.
  7. Henley J, Poo MM. Guiding neuronal growth cones using Ca2+ signals. Trends Cell Biol. 2004;14(6):320-30. https://doi.org/10.1016/j.tcb.2004.04.006
  8. Hoeger-Bement MK, Sluka KA. Phosphorylation of CREB and mechanical hyperalgesia is reversed by blockade of the cAMP pathway in a time-dependent manner after repeated intramuscular acid injections. J Neurosci. 2003;23(13):5437-45.
  9. Ikeda H, Heinke B, Ruscheweyh R, Sandkuhler J. Synaptic plasticity in spinal lamina I projection neurons that mediate hyperalgesia. Science. 2003;299(5610):1237-40. https://doi.org/10.1126/science.1080659
  10. Kang YM, Lee MK, Yang GY, Bae YC, Ahn DK. Participation of nitric oxide pathways in interleukin 1$\beta$-induced mechanical allodynia in the orogicial area of rats. Int J Oral Biol. 2009; 34(1):1-6.
  11. LaMotte RH, Thalhammer JG. Torebjork HE, Robinson CJ. Peripheral neural correlates of magnitude of cutaneous pain and hyperalgesia: a comparison of neural events in monkey with sensory judgements in human. J Neurophysiol 1983; 50;1-26. https://doi.org/10.1152/jn.1983.50.1.1
  12. Light AR, Trevino DL, Perl ER. Morphological features of functionally defined neurons in the marginal zone and substantia gelatinosa of the spinal dorsal horn. J Comp Neurol. 1979;186:151-172. https://doi.org/10.1002/cne.901860204
  13. Ma W, Du W, Eisenach JC. Role for both spinal cord COX-1 and COX-2 in maintenance of mechanical hypersensitivity following peripheral nerve injury. Brain Res. 2002;937(1- 2):94-9. https://doi.org/10.1016/S0006-8993(02)02593-3
  14. Mills CD, Johnson KM, Hulsebosch CE. Group I metabotropic glutamate receptors in spinal cord injury: roles in neuroprotection and thedevelopment of chronic central pain. J Neurotrauma. 2002;19(1):23-42. https://doi.org/10.1089/089771502753460213
  15. Moore KA, Baba H, Woolf CJ. Synaptic transmission and plasticity in the superficial dorsal horn. Prog Brain Res. 2000;129:63-80.
  16. Nishiyama M, Hoshino A, Tsai L, Henley JR, Goshima Y, Tessier-Lavigne M, Poo MM, Hong K. Cyclic AMP/GMPdependent modulation of Ca2+ channels sets the polarity of nerve growth-cone turning. Nature. 2003;423(6943):990-5. https://doi.org/10.1038/nature01751
  17. Parada CA, Reichling DB, Levine JD. Chronic hyperalgesic priming in the rat involves a novel interaction between cAMP and PKCepsilon second messenger pathways. Pain. 2005; 113(1-2):185-90. https://doi.org/10.1016/j.pain.2004.10.021
  18. Pockett S. Spinal cord synaptic plasticity and chronic pain. Anesth Analg. 1995;80(1);173-9.
  19. Randic M. Plasticity of excitatory synaptic transmission in the spinal cord dorsal horn. Prog Brain Res. 1996;113:463-506.
  20. Randic M, Jiang MC, Cerne R. Long-term potentiation and long-term depression of primary afferent neurotransmission in the rat spinal cord. J Neurosci. 1993;13:5228-5241.
  21. Rygh LJ, Tjolsen A, Hole K, Svendsen F. Cellular memory in spinal nociceptive circuitry. Scand J Psychol. 43(2);153-9, 2002. https://doi.org/10.1111/1467-9450.00281
  22. Rygh LJ, Svendsen F, Hole K, Tjolsen A. Natural noxious stimulation can induce long-term increase of spinal nociceptive responses. Pain. 1999;82:305-310. https://doi.org/10.1016/S0304-3959(99)00056-1
  23. Sandkuhler J, Benrath J, Brechtel C, Ruscheweyh R, Heinke B. Synaptic mechanisms of hyperalgesia. Prog Brain Res. 2000;129:81-100.
  24. Sandkuhler J, Chen JG, Cheng G, Randic M. Low-frequency stimulation of afferent Adelta-fibers induces long-term depression at primary afferent synapses with substantia gelatinosa neurons in the rat. J Neurosci. 1997;17(16):6483-91.
  25. Sugiura Y, Terui N, Hosoya Y. Difference in distribution of central terminals between visceral and somatic unmyelinated (C) primary afferent fibers. J Neurophysiol. 1989; 62(4):834- 840. https://doi.org/10.1152/jn.1989.62.4.834
  26. Svendsen F, Tjolsen A, Gjerstad J, Hole K. Long term potentiation of single WDR neurons in spinalized rats. Brain Res. 1999;816:487-492. https://doi.org/10.1016/S0006-8993(98)01250-5
  27. Tao YX, Hassan A, Haddad E, Johns RA. Expression and action of cyclic GMP-dependent protein kinase Ialpha in inflammatory hyperalgesia in rat spinal cord. Neuroscience. 2000;95(2):525-33.
  28. Tegeder I, Del Turco D, Schmidtko A, Sausbier M, Feil R, Hofmann F, Deller T, Ruth P, Geisslinger G. Reduced inflammatory hyperalgesia with preservation of acute thermal nociception in mice lacking cGMP-dependent protein kinase I. Proc Natl Acad Sci U S A. 2004 ;101(9):3253-7. https://doi.org/10.1073/pnas.0304076101
  29. Torebjork HE, Lundberg LE, LaMotte RH. Central changes in processing of mechanoreceptive input in capsaicin-induced secondary hyperalgesia in humans. J Physiol (Lond). 1992; 448:765-80. https://doi.org/10.1113/jphysiol.1992.sp019069
  30. Wen Z, Zheng JQ. Directional guidance of nerve growth cones. Curr Opin Neurobiol. 2006;16(1):52-58. https://doi.org/10.1016/j.conb.2005.12.005
  31. Willis WD Jr. Is central sensitization of nociceptive transmission in the spinal cord a variety of long-term potentiation? Neuroreport. 1997;8(16):3427-30. https://doi.org/10.1097/00001756-199711100-00002
  32. Willis WD. Long-term potentiation in spinothalamic neurons. Brain Res Brain Res Rev. 2002;40(1-3):202-14. https://doi.org/10.1016/S0165-0173(02)00202-3
  33. Woolf CJ, Doubell TP. The pathophysiology of chronic painincreased sensitivity to low threshold A beta-fiber inputs. Curr Opin Neurobiol. 1994;4:525-534. https://doi.org/10.1016/0959-4388(94)90053-1
  34. Woolf CJ, Fitzgerald M. The properties of neurones recorded in the superficial dorsal horn of the rat spinal cord. J Comp Neurol. 1983;221(3):313-328. https://doi.org/10.1002/cne.902210307
  35. Yoo S, Lee SH, Choi BH, Yeom JB, Ho WK, Earm YE. Dual effect of nitric oxide on the hyperpolarization-activated inward current (I(f)) in sino-atrial node cells of the rabbit. J Mol Cell Cardiol. 1998;30(12):2729-38. https://doi.org/10.1006/jmcc.1998.0845
  36. Yoshimura M, Jessell T. Amino acid-mediated EPSPs at primary afferent synapses with substantia gelatinosa neurones in the rat spinal cord. J Physiol (Lond). 1990; 430:315-35. https://doi.org/10.1113/jphysiol.1990.sp018293
  37. Yoshimura M, Jessell T. Membrane properties of rat substantia gelatinosa neurons in vitro. J Neurophysiol. 1989;62:109-18. https://doi.org/10.1152/jn.1989.62.1.109