DOI QR코드

DOI QR Code

Effects of TRPV1 in formalin-induced nociceptive behavior in the orofacial area of rats

흰쥐의 구강악안면 영역에서 포르말린 통증행위반응에 TRPV1 채널의 영향

  • Received : 2013.11.25
  • Accepted : 2014.01.09
  • Published : 2014.01.31

Abstract

The present study investigated the inflammatory hypersensitivity following activation of the transient receptor potential vanilloid receptor-1(TRPV1) in rats. Experiments were carried out on male Sprague-Dawley rats weighing 220-260g. Following an subcutaneous injection of 5% formalin in the orofacial area, nociceptive scratching behavior was recorded for 9 successive 5-min intervals in rats. The subcutaneous injection of $25{\mu}L$ of 5% formalin produced noxious scratching behavior. Injection of capsaicin, TRPV1 agonist, alone into the vibrissa pad did not produced nociceptive behavior. After subcutaneous injection of capsaicin(0$0.1{\mu}g$, $1{\mu}g/10{\mu}L$) in the formalin-treated rats, nociceptive scratching behavior was recorded for 9 successive 5-min internals. Injection of capsaicin into the vibrissa pad significantly increased the number of scratches at 1 hours after injection. Noxious behavioral responses induced by subcutaneous capsaicin injection were significantly potentiated in formalin-treated rats. Pre or post-treatment with iodo-resinaferatoxin(IRTX), TRPV1 antagonist, significantly attenuated increased nociceptive behavior. These findings suggest that activation of the TRPV1 enhanced formalin-induced inflammatory pain in the orofacial area of rats.

본 연구는 TRPV1 채널의 활성화가 염증성 통증반응 조절에 관여하는지에 관해 조사하였다. 수컷의 Sprague-Dawley계 흰 쥐 (220-260g)을 사용하였으며, 통증행위반응은 약물 주입 후 총 45분간 안면부를 긁거나 문지르는 행위를 지표로 간주하였다. 5% formalin($25{\mu}L$)을 단독투여 한 그룹에서는 유의한 통증행위반응을 관찰할 수 있었으나, capsaicin($0.1{\mu}g$, $1{\mu}g/10{\mu}L$)의 단독 투여한 그룹에서는 통증행위반응의 변화가 나타나지 않았다. 실험동물의 안면부에 TRPV1 채널의 효현제인 capsaicin 을 1시간 전에 주입한 후 동일 부위로 5% formalin 을 투여하게 되면 유의하게 증가된 통증행위반응을 관찰할 수 있었다. 증가된 통증행위반응은 TRPV1의 억제제인 I-RTX의 전처리에 의해 효과적으로 경감되었다(p<0.05). 이상의 결과들은 5% formalin으로 유발된 안면부 염증성 통증행위반응에 TRPV1의 활성화가 통증전도에 영향을 미칠 수 있음을 제시한다.

Keywords

References

  1. M. J. Caterina, M. A. Schumacher, M. Tominag a, T. A. Rosen, Levine, J. D. Julius D, The capsaicin receptor: a heat-activated ion channel in the pain pathway, Nature, Vol.389, No.6653, pp.816-824, 1997 DOI: http://dx.doi.org/10.1038/39807
  2. M. Tominaga, M. J. Caterina, A. B. Malmberg, T. A. Rosen, H. Gilbert, K. Skinner, Raumann, B. E. Basbaum AI, D. Julius, The cloned capsaicin receptor integrates multiple pain-producing stimuli, Neuron, Vol.21, No.3, pp.531-543, 1998 DOI: http://dx.doi.org/10.1016/S0896-6273(00)80564-4
  3. M. J. Caterina, D. Julius, The vanilloid receptor : a molecular gateway to the pain pathway, Annu Rev Neurosci, Vol.24, No.1, pp.487-517, 2001 DOI: http://dx.doi.org/10.1146/annurev.neuro.24.1.487
  4. L. Pei, C. Y. Lin, J. P. Dai, G. F. Yin, Facial pain induces the alteration of transient receptor potential vanilloid receptor 1 expression in rat trigeminal ganglion, Neurosci Bull, Vol.23, No.2, pp.92-100, 2007 DOI: http://dx.doi.org/10.1007/s12264-007-0013-2
  5. Y. Kanai, T. Hara, A, Imai, Participation of the spinal TRPV1 receptors in formalin-evoked pain transduction: a study using a selective TRPV1 antagonist, iodo-resiniferatoxin, J Pharm Pharma-col, Vol.58, No.4, pp.489-93, 2006 DOI: http://dx.doi.org/10.1211/jpp.58.4.0008
  6. R. R. Ji, T. A. Samad, S. X. Jin, R. Schmoll, C. J. Woolf, p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia, Neuron, Vol.36, No.1, pp.57-68, 2002 DOI: http://dx.doi.org/10.1016/S0896-6273(02)00908-X
  7. H. Luo, J. Cheng, J. S. Han, Y. Wan, Change of vanilloid receptor 1 expression in dorsal root ganglion and spinal dorsal horn during inflammatory nociception induced by complete Freund's adjuvant in rats, NeuroReport, Vol.15, No.4, pp.655-658, 2004 DOI: http://dx.doi.org/10.1097/00001756-200403220-00016
  8. M. McMahon, J. Grossman, J. FitzGerald, E. Dahlin-Lee, D. J. Wallace, B. Y. Thong, H. Badsha, K. Kalunian, C. Charles, M. Navab, A. M. Fogelman, B. H. Hahn, Proinflammatory high-density lipoprotein as a biomarker for atherosclerosis in patients with systemic lupus erythematosus and rheumatoid arthritis, Arthritis Rheum, Vol.54, No.8, pp.2541-2549, 2006 DOI: http://dx.doi.org/10.1002/art.21976
  9. S. Sugiyo, D. Uehashi, F. Satoh, T. Abe, N. Yonehara, M. Kobayashi, M. Takemura, Effects of systemic bicuculline or morphine on formalin-evoked pain-related behaviour and c-Fos expression in trigeminal nuclei after formalin injection into the lip or tongue in rats, Exp Brain Res, Vol.196, No.2, pp.229-237, 2009 DOI: http://dx.doi.org/10.1007/s00221-009-1842-1
  10. M. K. Park, J. H. Lee, G. Y. Yang, K. A. Won, M. J. Kim, Y. Y. Park, Y. C. Bae, D. K. Ahn, Peripheral administration of NR2 antagonists attenuates orofacial formalin-induced nociceptive behavior in rats, Prog Neuropsychopharmacol Biol Psychiatry, Vol.35, No.4, pp.982-986, 2011 DOI: http://dx.doi.org/10.1016/j.pnpbp.2011.01.018
  11. K. A. Won, Y. M. Kang, M. K. Lee, M. K. Park, J. S. Ju, Y. C. Bae YC, D. K. Ahn, Participation of Microglial p38 MAPK in Formalin-Induced Temporomandibular Joint Nociception in Rats, J Orofac Pain, Vol.26, No.2, pp.132-41, 2012
  12. H. H. Chuang, E. D. Prescott, Kong H, Shields S, Jordt SE, Basbaum AI, Chao MV, Julius D. Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5) P2-mediated inhibition, Nature, Vol.411, No.6840, pp.957-962, 2001 DOI: http://dx.doi.org/10.1038/35082088
  13. C. J. LaBuda, P. N. Fuchs, A comparison of chronic aspartame exposure to aspirin on inflammation, hyperalgesia and open field activity following carrageenan-induced monoart-hritis, Life Sci, Vol.69, No.4, pp.443-454, 2001 DOI: http://dx.doi.org/10.1016/S0024-3205(01)01136-5
  14. G. Y. Yang, Y. H. Park, M. K. Lee, S. K. Kim, D. K. Ahn, Compression of The Trigeminal Ganglion Enhances Nociceptive Behavior Produced by Formalin in The Orofacial Area of Rats, International Journal of Oral Biology, Vol.33, No.4, pp.155-162. 2008
  15. Y. Han, Y. Li, X. Xiao, J. Liu, X. L. Meng, F. Y. Liu, G. G. Xing, Y. Wan, Formaldehyde up-regulates TRPV1 through MAPK and PI3K signaling pathways in a rat model of bone cancer pain, Neurosci Bull, Vol.28, No.2, pp.165-172, 2012 DOI: http://dx.doi.org/10.1007/s12264-012-1211-0
  16. D. W. Dandy, Concerning the cause of trigeminal neuralgia, Am J Surg, Vol.24, pp.447-455, 1934 DOI: http://dx.doi.org/10.1016/S0002-9610(34)90403-7
  17. C. Y. Jung, H. S. Choi, J. S. Ju, H. S. Park, T. G. Kwon, Y. C. Bae, D. K. Ahn, Central metabotropic glutamate receptors differentially participate in IL-$1{\beta}$-induced mechanical allodynia in the orofacial area of conscious rats, J Pain, Vol.7, No.10, pp.747-756, 2006 DOI: http://dx.doi.org/10.1016/j.jpain.2006.03.007
  18. D. K. Ahn, J. M. Chae, H. S. Choi, H. M. Kyung, O. W. Kwon, H. S. Park, D. H. Youn, Y. C. Bae, Central cyclooxygenase inhibitors reduced IL-1beta-induced hyperalgesia in temporomandibular joint of freely moving rats, Pain, Vol.117, No.1-2, pp.204-213, 2005 DOI: http://dx.doi.org/10.1016/j.pain.2005.06.009
  19. B. E. Cairns, B. J. Sessle, J. W. Hu, Evidence that excitatory amino acid receptors within the temporomandibular joint region are involved in the reflex activation of the jaw muscles, J Neurosci, Vol.18, No.19, pp.8056-8064, 1998 https://doi.org/10.1523/JNEUROSCI.18-19-08056.1998
  20. K. Iwata, A. Tashiro, Y. Tsuboi, T. Imai, R. Sumino, T. Morimoto, R. Dubner, K. Ren, Medullary dorsal horn neuronal activity in rats with persistent temporomandibular joint and perioral inflammation, J Neurophysiol, Vol.82, No.3, pp.1244-1253, 1999 https://doi.org/10.1152/jn.1999.82.3.1244
  21. Q. Zhou, H, Imbe, R, Dubner, K, Ren, Persistent Fos protein expression after orofacial deep or cutaneous tissue inflammation in rats:implications for persistent orofacial pain, J Comp Neurol, Vol.412, No.2, pp.276-291, 1999 DOI: http://dx.doi.org/10.1002/(SICI)1096-9861 (19990920) 412:2<276::AID-CNE7>3.0.CO;2-9
  22. H. S. Choi, J. S. Ju, H. J. Lee, B. C. Kim, J. S. Park, D. K. Ahn, Effects of intracisternal injection of interleukin-6 on nociceptive jaw opening reflex and orofacial formalin test in freely moving rats, Brain Res Bull, Vol.59, No.5, pp.365-370, 2003 DOI: http://dx.doi.org/10.1016/S0361-9230(02)00931-0
  23. L. A. Roberts, M. Connor, TRPV1 antagonists as a potential treatment for hyperalgesia, Recent Pat CNS Drug Discov, Vol.1, No.1, pp.65-76, 2006 DOI: http://dx.doi.org/10.2174/157488906775245309
  24. A. R. Santos, J. B. Calixto, Ruthenium red and capsazepine antinociceptive effect in formalin and capsaicin models of pain in mice, Neurosci Lett, Vol.235, No.1-2, pp.73-76, 1997 DOI: http://dx.doi.org/10.1016/S0304-3940(97)00722-2
  25. A. Krzyzanowska, C. Avendano, Behavioral testing in rodent models of orofacial neuropathic and inflammatory pain, Brain Behav, Vol.2, No.5, pp.678-697, 2012 DOI: http://dx.doi.org/10.1002/brb3.85
  26. Y. Kanai, E. Nakazato, A. Fujiuchi, T. Hara, A. Imai, Involvement of an increased spinal TRPV1 sensitization through its up-regulation in mechanical allodynia of CCI rats, Neuropharmacology, Vol.49, No.7, pp.977-984, 2005 DOI: http://dx.doi.org/10.1016/j.neuropharm.2005.05.003
  27. S. Stander, C. Moormann, M. Schumacher, J. Buddenkotte, M. Artuc, V. Shpacovitch, T. Brzoska, U. Lippert, B. M. Henz, T. A. Luger, D. Metze, M. Steinhoff, Expression of vanilloid receptor subtype 1 in cutaneous sensory nerve fibers, mast cells, and epithelial cells of appendage structures, Exp Dermatol, Vol.13, No.3, pp.129-139, 2004 DOI: http://dx.doi.org/10.1111/j.0906-6705.2004.0178.x
  28. M. B. Urtado, G. H. Gameiro, C. H. Tambeli, L. Fischer, C. B. Urtado, M. C. de Arruda Veiga, Involvement of peripheral TRPV1 in TMJ hyperalgesia induced by ethanol withdrawal, Life Sci, Vol.81, No.23-24, pp.1622-1626, 2007 DOI: http://dx.doi.org/10.1016/j.lfs.2007.10.002