International Journal of Oral Biology

The Korean Academy of Oral Biology (대한구강생물학회)
권호 표지

A Blockade of the Central MAPK Pathway Attenuates Referred Pain in Rats with Complete Freund's Adjuvant -Induced Inflammation of the Temporomandibular Joint

  • Won, Kyoung-A. (Department of Oral Physiology, Kyungpook National University) ;
  • Lim, Nak-H. (Department of Oral Physiology, Kyungpook National University) ;
  • Lee, Min-K. (Department of Oral Physiology, Kyungpook National University) ;
  • Park, Min-K. (Department of Oral Physiology, Kyungpook National University) ;
  • Yang, Gwi-Y. (Department of Oral Physiology, Kyungpook National University) ;
  • Park, Yoon-Yub (Department of Physiology, School of Medicine, Catholic University of Daegu) ;
  • Ahn, Dong-K. (Department of Oral Physiology, Kyungpook National University) ;
  • Bae, Yong-C. (Department of Oral Anatomy, Kyungpook National University)
  • Received : 2010.08.04
  • Accepted : 2010.09.03
  • Published : 2010.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

We investigated the role of the central MAPK pathways in extra-territorial (referred) pain resulting from inflammation of the temporomandibular joint (TMJ). Experiments were carried out on male Sprague-Dawley rats weighing 220-280 g. Under anesthesia, these animals were injected with $50\;{\mu}L$ of complete Freund's adjuvant (CFA) into the TMJ using a Hamilton syringe. In the control group, saline was injected into the TMJ. To identify the extent of inflammation of the TMJ, Evans blue dye (0.1%, 5 mg/kg) was injected intravenously at 1, 3, 6, 9, 12 and 15 days after CFA injection. The concentration of Evans blue dye in the extracted TMJ tissue was found to be significantly higher in the CFA-treated animals than in the saline-treated group. Air-puff thresholds in the vibrissa pad area were evaluated 3 days before and at 3, 6, 9, 12, 15 and 18 days after CFA injection into the TMJ. Referred mechanical allodynia was established at 3 days, remained until 12 days, and recovered to preoperative levels at 18 days after CFA injection. This referred mechanical allodynia was observed in contralateral side area. To investigate the role of central MAPK pathways, MAPK inhibitors ($10\;{\mu}g$) were administrated intracisternally 9 days after CFA injection. SB203580, a p38 MAPK inhibitor, significantly attenuated referred mechanical allodynia, as compared with the vehicle group. PD98059, a MEK inhibitor, also reduced CFA-induced referred mechanical allodynia. These results suggest that TMJ inflammation produces extra-territorial mechanical allodynia, and that this is mediated by central MAPK pathways.

Keywords

References

  1. Adwanikar H, Karim F, Gereau RW. Inflammation persistently enhances nocifensive behaviors mediated by spinal group I mGluRs through sustained ERK activation. Pain. 2004;111: 125-35. https://doi.org/10.1016/j.pain.2004.06.009
  2. Ahn DK, Lee SY, Han SR, Ju JS, Yang GY, Lee MK, Youn DH, Bae YC. Intratrigeminal ganglionic injection of LPA causes neuropathic pain-like behavior and demyelination in rats. Pain. 2009b;146:114-20. https://doi.org/10.1016/j.pain.2009.07.012
  3. Ahn DK, Lim EJ, Kim BC, Yang GY, Lee MK, Ju JS, Han SR, Bae YC. Compression of the trigeminal ganglion produces prolonged nociceptive behavior in rats. Eur J Pain. 2009a; 13:568-75. https://doi.org/10.1016/j.ejpain.2008.07.008
  4. Boyle DL, Jones TL, Hammaker D, Svensson CI, Rosengren S, Albani S, Sorkin L, Firestein GS. Regulation of peripheral inflammation by spinal p38 MAP kinase in rats. PLoS Med. 2006;3:1616-24.
  5. Chacur M, Milligan ED, Gazda LS, Armstrong C, Wang H, Tracey KJ, Maier SF, Watkins LR. A new model of sciatic inflammatory neuritis (SIN): induction of unilateral and bilateral mechanical allodynia following acute unilateral perisciatic immune activation in rats. Pain. 2001;94:231-44. https://doi.org/10.1016/S0304-3959(01)00354-2
  6. Choi SS, Seo YJ, Shim EJ, Kwon MS, Lee JY, Ham YO, Suh HW. Involvement of phosphorylated Ca2+/calmodulindependent protein kinase II and phosphorylated extracellular signal-regulated protein in the mouse formalin pain model. Brain Res. 2006;1108:28-38. https://doi.org/10.1016/j.brainres.2006.06.048
  7. Crown ED, Ye Z, Johnson KM, Xu GY, McAdoo DJ, Hulsebosch CE. Increases in the activated forms of ERK 1/ 2, p38 MAPK, and CREB are correlated with the expression of at-level mechanical allodynia following spinal cord injury. Exp Neurol. 2006;199:397-407. https://doi.org/10.1016/j.expneurol.2006.01.003
  8. Fricton JR, Kroening R, Haley D, Siegert R. Myofascial pain syndrome of thehead and neck: a review of clinical characteristics of 164 patients. Oral Surg Oral Med Oral Pathol. 1985;60:615-23. https://doi.org/10.1016/0030-4220(85)90364-0
  9. Honda K, Kitagawa J, Sessle BJ, Kondo M, Tsuboi Y, Yonehara Y, Iwata K. Mechanisms involved in an increment of multimodal excitability of medullary and upper cervical dorsal horn neurons following cutaneous capsaicin treatment. Mol Pain. 2008;4:59 https://doi.org/10.1186/1744-8069-4-59
  10. Huang D, Yu B. The mirror-image pain: an unclered phenomenon and its possible mechanism. Neurosci Biobehav Rev. 2010; 34:528-32. https://doi.org/10.1016/j.neubiorev.2009.10.011
  11. Jacquin MF, Chiaia NL, Rhoades RW. Trigeminal projections to contralateral dorsal horn: central extent, peripheral origins, and plasticity. Somatosens Mot Res. 1990;7:153-83. https://doi.org/10.3109/08990229009144705
  12. Ji RR, Gereau RW 4th, Malcangio M, Strichartz GR. MAP kinase and pain. Brain Res Rev. 2009;60:135-48. https://doi.org/10.1016/j.brainresrev.2008.12.011
  13. Ji RR, Befort K, Brenner GJ, Woolf CJ. ERK MAP kinase activation in superficial spinal cord neurons induces prodynorphin and NK-1 upregulation and contributes to persistent inflammatory pain hypersensitivity. J Neurosci. 2002;22:478-85.
  14. Ji RR, Baba H, Brenner GJ, Woolf CJ. Nociceptive-specific activation of ERK in spinal neurons contributes to pain hyperrsensitivity. Nat Neurosci. 1999;2:1114-9. https://doi.org/10.1038/16040
  15. Karim F, Hu HJ, Adwanikar H, Kaplan D, Gereau RW 4th. Impaired inflammatory pain and thermal hyperalgesia in mice expressing neuron-specific dominant negative mitogen activated protein kinase kinase (MEK). Mol Pain. 2006;2:2. https://doi.org/10.1186/1744-8069-2-2
  16. Koltzenburg M, Wall PD, McMachon SB. Does the right side know what the left is doing? Trends Neurosci. 1999;22:122-7. https://doi.org/10.1016/S0166-2236(98)01302-2
  17. Kumar S, Boehm J, Lee JC. p38 MAP kinases: key signalling molecules as therapeutic targets for inflammatory diseases. Nat Rev Drug Discov. 2003;2:717-26. https://doi.org/10.1038/nrd1177
  18. McNeill C. Management of temporomandibular disorders: concepts and controversies. J Prosthet Dent. 1997;77:510-22. https://doi.org/10.1016/S0022-3913(97)70145-8
  19. Milligan ED, Twinnig C, Chacur M, Biedenkapp J, O'Connor K, Poole S, Tracey K, Martin D, Maier SF, Watkins LR. Spinal glia and proinflammatory cytokines mediated mirro-image neuropathic pain in rats. J Neurosci. 2003;23:1026-40.
  20. Obata K, Noguchi K. MAPK activation in nociceptive neurons and pain hypersensitivity. Life Science. 2004;74:2643-53. https://doi.org/10.1016/j.lfs.2004.01.007
  21. Okeson JP. Management of temporomandibular disorders and occlusion. 4th ed. St Louis: Mosby; 1998:169-71.
  22. Okeson JP. Orofacial pain: Guidelines for assessment, diagnosis,and management American Academy of Orofacial Pain. Chicago: Quintessence; 1996:8-10.
  23. Okeson JP, Bell WE. Bell's orofacial pains. 5th ed. Chicago: Quintessence; 1995:61-81, 161-2, 266-9.
  24. Oral K, Bal Kucuk B, Ebeo lu B, Dinçer S. Etiology of temporomandibular disorder pain. Agri. 2009;21:89-94.
  25. Panneton WM, Klein BG, Jacpuin MF. Trigeminal projections to contralateral dorsal horn originate in midline hairy skin. Somatosens Mot Res. 1991;8:165-73. https://doi.org/10.3109/08990229109144741
  26. Ren K, Dubner R. An inflammation/hyperalgesia model for the study of orofacial pain. J Dent Res. 1996;75:217.
  27. Schreiber KL, Beitz AJ, Wilcox GL. Activation of spinal microglia in a murine model of peripheral inflammationinduced, long-lasting contralateral allodynia. Neurosci Lett. 2008;440:63-7. https://doi.org/10.1016/j.neulet.2008.05.044
  28. Tsuda M, Ishii S, Masuda T, Hasegawa S, Nakamura K, Nagata K, Yamashita T, Furue H, Tozaki-Saitoh H, Yoshimura M, Koizumi S, Shimizu T, Inoue K. Reduced pain behaviors and extracellular signal-related protein kinase activation in primary sensory neurons by peripheral tissue injury in mice lacking platelet-activating factor receptor. J Neurochem. 2007;102: 1658-68. https://doi.org/10.1111/j.1471-4159.2007.04796.x
  29. Wright EF. Referred craniofacial pain patterns in patients with temporomandibular disorder. J Am Dent Assoc. 2000;131: 1307-15. https://doi.org/10.14219/jada.archive.2000.0384
  30. Widmann C, Gibson S, Jarpe MB, Johnson GL. Mitogenactivated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev. 1999;79:143-80. https://doi.org/10.1152/physrev.1999.79.1.143
  31. Yang CS, Jung CY, Ju JS, Lee MK, Ahn DK. Intracisternal administration of mitogen-activated protein kinase inhibitors reduced IL-1beta-induced mirror-image mechanical allodynia in the orofacial area of rats. Neurosci Lett. 2005;387:32-7. https://doi.org/10.1016/j.neulet.2005.07.019
  32. Zhang FE, Cao JL, Zhang LC, Zeng YM. Activation of p38 mitogen-activated protein kinase in spinal cord contributes to chronic constriction injury-induced neuropathic pain. Sheng Li Xue Bao. 2005;57:545-51.