Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지

Attenuated Neuropathic Pain in CaV3.1 Null Mice

  • Na, Heung Sik (Department of Physiology, Korea University College of Medicine) ;
  • Choi, Soonwook (Center for Neural Science, Korea Institute of Science and Technology) ;
  • Kim, Junesun (Department of Physiology, Korea University College of Medicine) ;
  • Park, Joonoh (Center for Neural Science, Korea Institute of Science and Technology) ;
  • Shin, Hee-Sup (Center for Neural Science, Korea Institute of Science and Technology)
  • Received : 2007.08.03
  • Accepted : 2007.10.31
  • Published : 2008.04.30
⟨ Previous Next ⟩

Abstract

To assess the role of $\alpha_{1G}$ T-type $Ca^{2+}$ channels in neuropathic pain after L5 spinal nerve ligation, we examined behavioral pain susceptibility in mice lacking $Ca_{V}3.1$ (${\alpha}_{1G}{^{-/-}}$), the gene encoding the pore-forming units of these channels. Reduced spontaneous pain responses and an increased threshold for paw withdrawal in response to mechanical stimulation were observed in these mice. The ${{\alpha}_{1G}}^{-/-}$ mice also showed attenuated thermal hyperalgesia in response to both low-(IR30) and high-intensity (IR60) infrared stimulation. Our results reveal the importance of ${\alpha}_{1G}$ T-type $Ca^{2+}$ channels in the development of neuropathic pain, and suggest that selective modulation of ${\alpha}_{1G}$ subtype channels may provide a novel approach to the treatment of allodynia and hyperalgesia.

Keywords

Acknowledgement

Supported by : Ministry of Science and Technology

References

  1. Back, S.K., Kim, J.S., Hong, S.K., and Na, H.S. (2003). Ascending pathways for mechanical allodynia in a rat model of neuropathic pain. Neuroreport 14, 1623-1626 https://doi.org/10.1097/00001756-200308260-00016
  2. Baron, R. (2000). Peripheral neuropathic pain: from mechanisms to symptoms. Clin. J. Pain 16, S12-20 https://doi.org/10.1097/00002508-200003000-00003
  3. Baron, R. (2006). Mechanisms of disease: neuropathic pain--a clinical perspective. Nat. Clin. Pract. 2, 95-106 https://doi.org/10.1038/ncpneuro0113
  4. Bennett, G.J., and Xie, Y.K. (1988). A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 33, 87-107 https://doi.org/10.1016/0304-3959(88)90209-6
  5. Bourinet, E., Alloui, A., Monteil, A., Barrere, C., Couette, B., Poirot, O., Pages, A., McRory, J., Snutch, T.P., Eschalier, A., et al. (2005). Silencing of the Cav3.2 T-type calcium channel gene in sensory neurons demonstrates its major role in nociception. EMBO J. 24, 315-324 https://doi.org/10.1038/sj.emboj.7600515
  6. Bourquin, A.F., Suveges, M., Pertin, M., Gilliard, N., Sardy, S., Davison, A.C., Spahn, D.R., and Decosterd, I. (2006). Assessment and analysis of mechanical allodynia-like behavior induced by spared nerve injury (SNI) in the mouse. Pain 122, 14. e1-14 https://doi.org/10.1016/j.pain.2006.01.023
  7. Carbone, E., and Lux, H.D. (1984). A low voltage-activated, fully inactivating Ca channel in vertebrate sensory neurones. Nature 310, 501-502 https://doi.org/10.1038/310501a0
  8. Chaplan, S.R., Bach, F.W., Pogrel, J.W., Chung, J.M., and Yaksh, T.L. (1994). Quantitative assessment of tactile allodynia in the rat paw. J. Neurosci. Methods 53, 55-63 https://doi.org/10.1016/0165-0270(94)90144-9
  9. Choi, S., Na, H.S., Kim, J., Lee, J., Lee, S., Kim, D., Park, J., Chen, C.C., Campbell, K.P., and Shin, H.S. (2007). Attenuated pain responses in mice lacking Ca(V)3.2 T-type channels. Genes Brain Behav. 6, 425-431 https://doi.org/10.1111/j.1601-183X.2006.00268.x
  10. Dixon, W.J. (1980). Efficient analysis of experimental observations. Annu. Rev. Pharmacol. Toxicol. 20, 441-462 https://doi.org/10.1146/annurev.pa.20.040180.002301
  11. Djouhri, L., Koutsikou, S., Fang, X., McMullan, S., and Lawson, S.N. (2006). Spontaneous pain, both neuropathic and inflammatory, is related to frequency of spontaneous firing in intact C-fiber nociceptors. J. Neurosci 26, 1281-1292 https://doi.org/10.1523/JNEUROSCI.3388-05.2006
  12. Dogrul, A., Gardell, L.R., Ossipov, M.H., Tulunay, F.C., Lai, J., and Porreca, F. (2003). Reversal of experimental neuropathic pain by T-type calcium channel blockers. Pain 105, 159-168 https://doi.org/10.1016/S0304-3959(03)00177-5
  13. Heinke, B., Balzer, E., and Sandkuhler, J. (2004). Pre- and postsynaptic contributions of voltage-dependent $Ca^2+$ channels to nociceptive transmission in rat spinal lamina I neurons. Eur. J. Neurosci. 19, 103-111 https://doi.org/10.1046/j.1460-9568.2003.03083.x
  14. Hirayama, T., Dostrovsky, J.O., Gorecki, J., Tasker, R.R., and Lenz, F.A. (1989). Recordings of abnormal activity in patients with deafferentation and central pain. Stereotact. Funct. Neurosurg. 52, 120-126 https://doi.org/10.1159/000099492
  15. Ikeda, H., Heinke, B., Ruscheweyh, R., and Sandkuhler, J. (2003). Synaptic plasticity in spinal lamina I projection neurons that mediate hyperalgesia. Science 299, 1237-1240 https://doi.org/10.1126/science.1080659
  16. Jeanmonod, D., Magnin, M., and Morel, A. (1993). Thalamus and neurogenic pain: physiological, anatomical and clinical data. Neuroreport 4, 475-478 https://doi.org/10.1097/00001756-199305000-00003
  17. Jeanmonod, D., Magnin, M., and Morel, A. (1996). Lowthreshold calcium spike bursts in the human thalamus. Common physiopathology for sensory, motor and limbic positive symptoms. Brain 119 (Pt 2), 363-375 https://doi.org/10.1093/brain/119.2.363
  18. Jevtovic-Todorovic, V., and Todorovic, S.M. (2006). The role of peripheral T-type calcium channels in pain transmission. Cell Calcium 40, 197-203 https://doi.org/10.1016/j.ceca.2006.04.024
  19. Kim, D., Park, D., Choi, S., Lee, S., Sun, M., Kim, C., and Shin, H.S. (2003). Thalamic control of visceral nociception mediated by T-type $Ca^2+$ channels. Science 302, 117-119 https://doi.org/10.1126/science.1088886
  20. Kim, D., Song, I., Keum, S., Lee, T., Jeong, M.J., Kim, S.S., McEnery, M.W., and Shin, H.S. (2001). Lack of the burst firing of thalamocortical relay neurons and resistance to absence seizures in mice lacking alpha(1G) T-type $Ca^2+$ channels. Neuron 31, 35-45 https://doi.org/10.1016/S0896-6273(01)00343-9
  21. Kim, K.S., Kim, J., Back, S.K., Im, J.Y., Na, H.S., and Han, P.L. (2007). Markedly attenuated acute and chronic pain responses in mice lacking adenylyl cyclase-5. Genes Brain Behav. 6, 120-127 https://doi.org/10.1111/j.1601-183X.2006.00238.x
  22. Kim, S.H., and Chung, J.M. (1992). An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 50, 355-363 https://doi.org/10.1016/0304-3959(92)90041-9
  23. Lee, J., Kim, D., and Shin, H.S. (2004). Lack of delta waves and sleep disturbances during non-rapid eye movement sleep in mice lacking alpha1G-subunit of T-type calcium channels. Proc. Natl. Acad. Sci. USA 101, 18195-18199
  24. Lee, Y., Lee, C.H., and Oh, U. (2005). Painful channels in sensory neurons. Mol. Cells 20, 315-324
  25. Lenz, F.A., Kwan, H.C., Dostrovsky, J.O., and Tasker, R.R. (1989). Characteristics of the bursting pattern of action potentials that occurs in the thalamus of patients with central pain. Brain Res. 496, 357-360 https://doi.org/10.1016/0006-8993(89)91088-3
  26. Llinas, R., and Jahnsen, H. (1982). Electrophysiology of mammalian thalamic neurones in vitro. Nature 297, 406-408 https://doi.org/10.1038/297406a0
  27. Llinas, R., and Yarom, Y. (1981). Electrophysiology of mammalian inferior olivary neurones in vitro. Different types of voltage- dependent ionic conductances. J. Physiol. 315, 549-567 https://doi.org/10.1113/jphysiol.1981.sp013763
  28. Llinas, R.R., Ribary, U., Jeanmonod, D., Kronberg, E., and Mitra, P.P. (1999). Thalamocortical dysrhythmia: a neurological and neuropsychiatric syndrome characterized by magnetoencephalography. Proc. Natl. Acad. Sci. USA 96, 15222-15227
  29. Malmberg, A.B., and Basbaum, A.I. (1998). Partial sciatic nerve injury in the mouse as a model of neuropathic pain: behavioral and neuroanatomical correlates. Pain 76, 215-222 https://doi.org/10.1016/S0304-3959(98)00045-1
  30. Matthews, E.A., and Dickenson, A.H. (2001). Effects of ethosuximide, a T-type $Ca^2+$ channel blocker, on dorsal horn neuronal responses in rats. Eur. J. Pharmacol. 415, 141-149 https://doi.org/10.1016/S0014-2999(01)00812-3
  31. Minert, A., Gabay, E., Dominguez, C., Wiesenfeld-Hallin, Z., and Devor, M. (2007). Spontaneous pain following spinal nerve injury in mice. Exp. Neurol. 206, 220-230 https://doi.org/10.1016/j.expneurol.2007.04.011
  32. Saade, N.E., Baliki, M., El-Khoury, C., Hawwa, N., Atweh, S.F., Apkarian, A.V., and Jabbur, S.J. (2002). The role of the dorsal columns in neuropathic behavior: evidence for plasticity and non-specificity. Neuroscience 115, 403-413 https://doi.org/10.1016/S0306-4522(02)00417-7
  33. Sukhotinsky, I., Ben-Dor, E., Raber, P., and Devor, M. (2004). Key role of the dorsal root ganglion in neuropathic tactile hypersensibility. Eur. J. Pain 8, 135-143 https://doi.org/10.1016/S1090-3801(03)00086-7
  34. Talley, E.M., Cribbs, L.L., Lee, J.H., Daud, A., Perez-Reyes, E., and Bayliss, D.A. (1999). Differential distribution of three members of a gene family encoding low voltage-activated (Ttype) calcium channels. J. Neurosci. 19, 1895-1911 https://doi.org/10.1523/JNEUROSCI.19-06-01895.1999
  35. Todorovic, S.M., Meyenburg, A., and Jevtovic-Todorovic, V. (2004). Redox modulation of peripheral T-type $Ca^2+$ channels in vivo: alteration of nerve injury-induced thermal hyperalgesia. Pain 109, 328-339 https://doi.org/10.1016/j.pain.2004.01.026
  36. Wen, X.J., Li, Z.J., Chen, Z.X., Fang, Z.Y., Yang, C.X., Li, H., and Zeng, Y.M. (2006). Intrathecal administration of Cav3.2 and Cav3.3 antisense oligonucleotide reverses tactile allodynia and thermal hyperalgesia in rats following chronic compression of dorsal root of ganglion. Acta Pharmacol. Sin. 27, 1547-1552 https://doi.org/10.1111/j.1745-7254.2006.00461.x
  37. Wood, J.N., Abrahamsen, B., Baker, M.D., Boorman, J.D., Donier, E., Drew, L.J., Nassar, M.A., Okuse, K., Seereeram, A., Stirling, C.L., et al. (2004). Ion channel activities implicated in pathological pain. Novartis Found. Symp. 261, 32?40; discussion 40-54
  38. Woolf, C.J., and Salter, M.W. (2000). Neuronal plasticity: increasing the gain in pain. Science 288, 1765-1769 https://doi.org/10.1126/science.288.5472.1765
  39. Woolf, C.J., Shortland, P., and Coggeshall, R.E. (1992). Peripheral nerve injury triggers central sprouting of myelinated afferents. Nature 355, 75-78 https://doi.org/10.1038/355075a0
  40. Xiao, H.S., Huang, Q.H., Zhang, F.X., Bao, L., Lu, Y.J., Guo, C., Yang, L., Huang, W.J., Fu, G., Xu, S.H., et al. (2002). Identification of gene expression profile of dorsal root ganglion in the rat peripheral axotomy model of neuropathic pain. Proc. Natl. Acad. Sci. USA 99, 8360-8365
  41. Yoon, Y.W., Na, H.S., and Chung, J.M. (1996). Contributions of injured and intact afferents to neuropathic pain in an experimental rat model. Pain 64, 27-36 https://doi.org/10.1016/0304-3959(95)00096-8
  42. Zimmermann, M. (2001). Pathobiology of neuropathic pain. Eur. J. Pharmacol. 429, 23-37 https://doi.org/10.1016/S0014-2999(01)01303-6