The Korean Journal of Pain

The Korean Pain Society (대한통증학회)
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The Expression of the Ca++ Channel α2δ Subunit and TRPM8 in the Dorsal Root Ganglion of Sympathetically Maintained Pain and Sympathetic Independent Pain Rat Models

교감신경 의존적 및 비의존적 신경병증 통증 쥐 모델 후근신경절에서 Ca++ Channel α2δ subunit와 TRPM8 발현

  • Han, Dong Woo (Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine) ;
  • Kweon, Tae Dong (Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine) ;
  • Kim, Yeon A (Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine) ;
  • Choi, Jong Bum (Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine) ;
  • Lee, Youn Woo (Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine)
  • 한동우 (연세대학교 의과대학 마취통증의학교실) ;
  • 권태동 (연세대학교 의과대학 마취통증의학교실) ;
  • 김연아 (연세대학교 의과대학 마취통증의학교실) ;
  • 최종범 (연세대학교 의과대학 마취통증의학교실) ;
  • 이윤우 (연세대학교 의과대학 마취통증의학교실)
  • Received : 2008.02.14
  • Accepted : 2008.03.18
  • Published : 2008.06.01
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Abstract

Background: Peripheral nerve injury induces up-regulation of the calcium channel alpha2delta (${\alpha}2{\delta}$) subunit and TRPM8 in the dorsal root ganglion (DRG) which might contribute to allodynia development. We investigated the expression of the ${\alpha}2{\delta}$ subunit and TRPM8 in the DRG of sympathetically maintained pain (SMP) and sympathetic independent pain (SIP) rat model. Methods: For the SMP model, the L5 and L6 spinal nerves were ligated tightly distal to the DRG. For the SIP model, the tibial and sural nerves were transected, while the common peroneal nerve was spared. After a 7 day postoperative period, tactile and cold allodynia were assessed using von Frey filaments and acetone drops, respectively. Expression of the ${\alpha}2{\delta}$ subunit and TRPM8 in the L5 and L6 DRG were subsequently examined by a Western blot. Results: There were no significant differences between the two models for the thresholds of tactile and cold allodynia. Expression of the ${\alpha}2{\delta}$ subunit in the ipsilateral DRG to the injury was increased as determined on a Western blot as compared to that in the contralateral or sham-operated DRG of the SMP model, but there was no difference in expression seen with the use of the SIP model. There was no difference in the expression of TRPM8 in the ipsilateral DRG to the injury and the contralateral or sham-operated DRG of either model. Conclusions: Up-regulation of the ${\alpha}2{\delta}$ subunit in injured DRG may play a role that contributes to tactile allodynia development in SMP, but not TRPM8 to cold allodynia after peripheral nerve injury.

Keywords

Acknowledgement

Supported by : 연세대학교

References

  1. Xie J, Park SK, Chung K, Chung JM: The effect of lumbar sympathectomy in the spinal nerve ligation model of neuropathic pain. J Pain 2001; 2: 270-8 https://doi.org/10.1054/jpai.2001.24559
  2. Han DW, Kweon TD, Kim KJ, Lee JS, Chang CH, Lee YW: Does the tibial and sural nerve transection model represent sympathetically independent pain? Yonsei Med J 2006; 47: 847-51 https://doi.org/10.3349/ymj.2006.47.6.847
  3. Roza C, Belmonte C, Viana F: Cold sensitivity in axotomized fibers of experimental neuromas in mice. Pain 2006; 120: 24-35 https://doi.org/10.1016/j.pain.2005.10.006
  4. Luo ZD, Calcutt NA, Higuera ES, Valder CR, Song YH, Svensson CI, et al: Injury type-specific calcium channel alpha 2 delta-1 subunit up-regulation in rat neuropathic pain models correlates with antiallodynic effects of gabapentin. J Pharmacol Exp Ther 2002; 303: 1199-205 https://doi.org/10.1124/jpet.102.041574
  5. Nealen ML, Gold MS, Thut PD, Caterina MJ: TRPM8 mRNA is expressed in a subset of cold-responsive trigeminal neurons from rat. J Neurophysiol 2003; 90: 515-20 https://doi.org/10.1152/jn.00843.2002
  6. Story GM, Peier AM, Reeve AJ, Eid SR, Mosbacher J, Hricik TR, et al: ANKTM1, a TRP-like channel expressed in nociceptive neurons, is activated by cold temperatures. Cell 2003; 112: 819-29 https://doi.org/10.1016/S0092-8674(03)00158-2
  7. Kim SH, Chung JM: An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 1992; 50: 355-63 https://doi.org/10.1016/0304-3959(92)90041-9
  8. Lee BH, Won R, Baik EJ, Lee SH, Moon CH: An animal model of neuropathic pain employing injury to the sciatic nerve branches. Neuroreport 2000; 11: 657-61 https://doi.org/10.1097/00001756-200003200-00002
  9. Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL: Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 1994; 53: 55-63 https://doi.org/10.1016/0165-0270(94)90144-9
  10. Attal N, Bouhassira D: Mechanisms of pain in peripheral neuropathy. Acta Neurol Scand 1999; 173(Suppl): 12-24
  11. Woolf CJ, Mannion RJ: Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet 1999; 353: 1959-64 https://doi.org/10.1016/S0140-6736(99)01307-0
  12. Takahashi K, Sato J, Mizumura K: Responses of C-fiber low threshold mechanoreceptors and nociceptors to cold were facilitated in rats persistently inflamed and hypersensitive to cold. Neurosci Res 2003; 47: 409-19 https://doi.org/10.1016/j.neures.2003.08.003
  13. Kim YI, Kim SH, Oh EJ, Sung B, Na HS, Han HC, et al: Some membrane property changes following axotomy in A delta-type DRG cells are related to cold allodynia in rat. Neuroreport 1999; 10: 1493-9 https://doi.org/10.1097/00001756-199905140-00019
  14. De Jongh KS, Warner C, Catterall WA: Subunits of purified calcium channels. Alpha 2 and delta are encoded by the same gene. J Biol Chem 1990; 265: 14738-41
  15. Klugbauer N, Marais E, Hofmann F: Calcium channel alpha2delta subunits: differential expression, function, and drug binding. J Bioenerg Biomembr 2003; 35: 639-47 https://doi.org/10.1023/B:JOBB.0000008028.41056.58
  16. Luo ZD, Chaplan SR, Higuera ES, Sorkin LS, Stauderman KA, Williams ME, et al: Upregulation of dorsal root ganglion (alpha)2(delta) calcium channel subunit and its correlation with allodynia in spinal nerve-injured rats. J Neurosci 2001; 21: 1868-75 https://doi.org/10.1523/JNEUROSCI.21-06-01868.2001
  17. Coull JA, Boudreau D, Bachand K, Prescott SA, Nault F, Sik A, et al: Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain. Nature 2003; 424: 938-42 https://doi.org/10.1038/nature01868
  18. McKemy DD, Neuhausser WM, Julius D: Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 2002; 416: 52-8 https://doi.org/10.1038/nature719
  19. Patapoutian A, Peier AM, Story GM, Viswanath V: Ther-moTRP channels and beyond: mechanisms of temperature sensation. Nat Rev Neurosci 2003; 4: 529-39 https://doi.org/10.1038/nrn1141
  20. Katsura H, Obata K, Mizushima T, Yamanaka H, Kobayashi K, Dai Y, et al: Antisense knock down of TRPA1, but not TRPM8, alleviates cold hyperalgesia after spinal nerve ligation in rats. Exp Neurol 2006; 200: 112-23 https://doi.org/10.1016/j.expneurol.2006.01.031
  21. Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA, Story GM, et al: A TRP channel that senses cold stimuli and menthol. Cell 2002; 108: 705-15 https://doi.org/10.1016/S0092-8674(02)00652-9
  22. Montell C: A mint of mutations in TRPM8 leads to cool results. Nat Neurosci 2006; 9: 466-8 https://doi.org/10.1038/nn0406-466
  23. Thut PD, Wrigley D, Gold MS: Cold transduction in rat trigeminal ganglia neurons in vitro. Neuroscience 2003; 119: 1071-83 https://doi.org/10.1016/S0306-4522(03)00225-2
  24. Askwith CC, Benson CJ, Welsh MJ, Snyder PM: DEG/ENaC ion channels involved in sensory transduction are modulated by cold temperature. Proc Natl Acad Sci USA 2001; 98: 6459-63
  25. Maingret F, Lauritzen I, Patel AJ, Heurteaux C, Reyes R, Lesage F, et al: TREK-1 is a heat-activated background K(+) channel. EMBO J 2000; 19: 2483-91 https://doi.org/10.1093/emboj/19.11.2483
  26. Hudson LJ, Bevan S, Wotherspoon G, Gentry C, Fox A, Winter J: VR1 protein expression increases in undamaged DRG neurons after partial nerve injury. Eur J Neurosci 2001; 13: 2105-14 https://doi.org/10.1046/j.0953-816x.2001.01591.x
  27. Tsuzuki K, Kondo E, Fukuoka T, Yi D, Tsujino H, Sakagami M, et al: Differential regulation of P2X(3) mRNA expression by peripheral nerve injury in intact and injured neurons in the rat sensory ganglia. Pain 2001; 91: 351-60 https://doi.org/10.1016/S0304-3959(00)00456-5
  28. Han DW, Kweon TD, Lee JS, Lee YW: Antiallodynic effect of pregabalin in rat models of sympathetically maintained and sympathetic independent neuropathic pain. Yonsei Med J 2007; 48: 41-7 https://doi.org/10.3349/ymj.2007.48.1.41