흰쥐 삼차신경감각핵에서 $P2X_3$와 TRPV1의 공존에 관한 연구

Coexpression of $P2X_3$ with TRPV1 in the Rat Trigeminal Sensory Nuclei

  • 문용석 (대구가톨릭대학교 의과대학 해부학교실) ;
  • 류창현 (경북대학교 치과대학 구강해부학교실) ;
  • 조이슬 (경북대학교 치과대학 구강해부학교실) ;
  • 김홍태 (대구가톨릭대학교 의과대학 해부학교실) ;
  • 박매자 (경북대학교 의과대학 해부학교실) ;
  • 백상규 (경북대학교 치과대학 구강해부학교실) ;
  • 문제일 (경북대학교 치과대학 구강해부학교실) ;
  • 김윤숙 (경북대학교 치과대학 구강해부학교실) ;
  • 배용철 (경북대학교 치과대학 구강해부학교실)
  • Moon, Yong-Suk (Department of Anatomy, School of Medicine, Catholic University of Daegu) ;
  • Ryoo, Chang-Hyun (Department of Oral Anatomy, School of Dentistry, Kyungpook National University) ;
  • Cho, Yi-Sul (Department of Oral Anatomy, School of Dentistry, Kyungpook National University) ;
  • Kim, Hong-Tae (Department of Anatomy, School of Medicine, Catholic University of Daegu) ;
  • Park, Mae-Ja (Department of Anatomy, School of Medicine, Kyungpook National University) ;
  • Paik, Sang-Kyoo (Department of Oral Anatomy, School of Dentistry, Kyungpook National University) ;
  • Moon, Che-Il (Department of Oral Anatomy, School of Dentistry, Kyungpook National University) ;
  • Kim, Yun-Sook (Department of Oral Anatomy, School of Dentistry, Kyungpook National University) ;
  • Bae, Yong-Chul (Department of Oral Anatomy, School of Dentistry, Kyungpook National University)
  • 발행 : 2008.09.30

초록

삼차신경계에서 $P2X_3$와 TRPV1 면역양성 일차들신경섬유는 통각정보의 전달에 중요한 역할을 한다. 본 연구에서는 삼차신경절 및 삼차신경꼬리핵에서 $P2X_3$와 TRPV1 면역양성 신경세포의 형태학적 특성 및 투사양식을 이해하기 위하여, 흰쥐 삼차신경절 및 삼차신경꼬리핵에서 $P2X_3$와 TRPV1에 대한 항체를 사용하여 형광면역염색법 및 형태계측학적인 기법을 시행하여 다음과 같은 결과를 얻었다. $P2X_3$ 면역양성 신경세포중 77.4%의 신경세포에서 (1,401/1,810) TRPV1이 동시에 발현되었으며, TRPV1 면역양성 신경세포중 51.9% (1,401/2,698)의 신경세포에서 $P2X_3$와 공존을 보였다. $P2X_3$와 TRPV1에 동시에 면역양성반응을 보이는 신경세포는 중간크기의 신경세포에서 주로 관찰되었으며, $P2X_3$ 혹은 TRPV1 면역양성 신경세포중 아주 작거나 큰 신경세포에서는 공존하지 않았다. 삼차신경꼬리핵에서 $P2X_3$ 면역양성 신경섬유 및 신경종말들은 제1층과 제2층에 분포하는데 주로 제2층의 안쪽부위에서 밀도가 높게 관찰되었으며, TRPV1 면역양성 신경섬유 및 신경종말들은 제1층과 제2층의 바깥쪽에서 밀도가 높게 관찰되었다. $P2X_3$와 TRPV1이 공존하는 신경섬유 및 신경종말들은 제2층의 안쪽과 바깥쪽의 경계부위에서 관찰되었다. 이러한 연구결과는 $P2X_3$와 TRPV1을 동시에 발현하는 신경세포는 구강안면영역에서 통각정보의 처리에 독특한 역할을 수행할 것이라는 것을 시사한다.

Trigeminal primary afferents expressing $P2X_3$ or transient receptor potential vanilloid 1 (TRPV1) are involved in the transmission of nociceptive information. In order to characterize $P2X_3$- and TRPV1-immunopositive neurons in the trigeminal ganglion (TG) and trigeminal caudal nucleus (Vc), we performed immunofluorescence experiments using anti-$P2X_3$ and anti-TRPV1 antisera and a morphometric analysis. 77.4% (1,401/1.801) of all the $P2X_3$-postive neurons coexpressed TRPV1 and 51.9% (1,401/2,698) of all the THFV1-immunopositive neurons also costained for $P2X_3$ in the TG. Immunoreactivity for both $P2X_3$ and TRPV1 were present in medium-sized neurons but not in small- and large-sized neurons. $P2X_3$ and/or TRPV1-immunopositive fibers were observed in the primary afferents and their associated axons in the Vc. These fibers and terminals were distributed in the superficial lamina of Vc: $P2X_3$-immunopositive fibers and terminals were distributed in the lamina I and II, expecially in the inner part of lamina II (lamina IIi), whereas TRPV1-immunopositive ones were densely detected in the lamina I and outer part of lamina II (lamina IIo). Immunopositive fibers and terminals for both $P2X_3$ and TRPV1 were observed on the border between lamina IIi and IIo. These results suggest that terminals coexpressing $P2X_3$ and TRPV1 are involved in specific roles in the transmission and processing of orofacial nociceptive information.

키워드

참고문헌

  1. Ambalavanar R, Moritani M, Dessem D: Trigeminal $P2X_{3}$ receptor expression differs from dorsal root ganglion and is modulated by deep tissue inflammation. Pain 117 : 280-291, 2005 https://doi.org/10.1016/j.pain.2005.06.029
  2. Aoki Y, Ohtori S, Takahashi K, Ino H, Ozawa T, Douya H, Chiba T, Moriya H: $P2X_{3}$-immunoreactive primary sensory neurons innervating lumbar intervertebral disc in rats. Brain Res 989 : 214-220, 2003 https://doi.org/10.1016/S0006-8993(03)03365-1
  3. Bradbury EJ, Burnstock G, McMahon SB: The expression of $P2X_{3}$ purinoreceptors in sensory neurons: effects of axotomy and glial-derived neurotrophic factor. Mol Cell Neurosci 12 : 256-268, 1998 https://doi.org/10.1006/mcne.1998.0719
  4. Burnstock G: Local mechanisms of blood flow control by perivascular nerves and endothelium. J Hypertens Suppl 8 : S95-106, 1990 https://doi.org/10.1097/00004872-199012000-00017
  5. Burnstock G: A unifying purinergic hypothesis for the initiation of pain. Lancet 347 : 1604-1605, 1996 https://doi.org/10.1016/S0140-6736(96)91082-X
  6. Burnstock G: P2X receptors in sensory neurones. Br J Anaesth 84 : 476-488, 2000 https://doi.org/10.1093/oxfordjournals.bja.a013473
  7. Caterina MJ, Julius D: The vanilloid receptor: a molecular gateway to the pain pathway. Annu Rev Neurosci 24 : 487-517, 2001 https://doi.org/10.1146/annurev.neuro.24.1.487
  8. Cockayne DA, Hamilton SG, Zhu QM, Dunn PM, Zhong Y, Novakovic S, Malmberg AB, Cain G, Berson A, Kassotakis L, Hedley L, Lachnit WG, Burnstock G, McMahon SB, Ford AP: Urinary bladder hyporeflexia and reduced pain-related behaviour in $P2X_{3}$-deficient mice. Nature 407 : 1011-1015, 2000 https://doi.org/10.1038/35039519
  9. Collo G, North RA, Kawashima E, Merlo-Pich E, Neidhart S, Surprenant A, Buell G: Cloning OF $P2X_{5}$ and $P2X_{6}$ receptors and the distribution and properties of an extended family of ATPgated ion channels. J Neurosci 16 : 2495-2507, 1996 https://doi.org/10.1523/JNEUROSCI.16-08-02495.1996
  10. Coutts AA, Jorizzo JL, Eady RA, Greaves MW, Burnstock G: Adenosine triphosphate-evoked vascular changes in human skin: mechanism of action. Eur J Pharmacol 76 : 391-401, 1981 https://doi.org/10.1016/0014-2999(81)90110-2
  11. Driessen B, Reimann W, Selve N, Friderichs E, Bultmann R: Antinociceptive effect of intrathecally administered P2-purinoceptor antagonists in rats. Brain Res 666 : 182-188, 1994 https://doi.org/10.1016/0006-8993(94)90770-6
  12. Eriksson J, Bongenhielm U, Kidd E, Matthews B, Fried K: Distribution of $P2X_{3}$ receptors in the rat trigeminal ganglion after inferior alveolar nerve injury. Neurosci Lett 254 : 37-40, 1998 https://doi.org/10.1016/S0304-3940(98)00656-9
  13. Gu JG, MacDermott AB: Activation of ATP P2X receptors elicits glutamate release from sensory neuron synapses. Nature 389 : 749-753, 1997 https://doi.org/10.1038/39639
  14. Guo A, Vulchanova L, Wang J, Li X, Elde R: Immunocytochemical localization of the vanilloid receptor 1 (VR1): relationship to neuropeptides, the P2X3 purinoceptor and IB4 binding sites. Eur J Neurosci 11 : 946-958, 1999 https://doi.org/10.1046/j.1460-9568.1999.00503.x
  15. Hamilton SG, Wade A, McMahon SB: The effects of inflammation and inflammatory mediators on nociceptive behaviour induced by ATP analogues in the rat. Br J Pharmacol 126 : 326-332, 1999 https://doi.org/10.1038/sj.bjp.0702258
  16. Hamilton SG, Warburton J, Bhattacharjee A, Ward J, McMahon SB: ATP in human skin elicits a dose-related pain response which is potentiated under conditions of hyperalgesia. Brain 123(Pt 6) : 1238-1246, 2000 https://doi.org/10.1093/brain/123.6.1238
  17. Helliwell RJ, McLatchie LM, Clarke M, Winter J, Bevan S, McIntyre P: Capsaicin sensitivity is associated with the expression of the vanilloid (capsaicin) receptor (VR1) mRNA in adult rat sensory ganglia. Neurosci Lett 250 : 177-180, 1998 https://doi.org/10.1016/S0304-3940(98)00475-3
  18. Hwang IK, Lee HY, Yoo KY, Seong NS, Chung HG, Kim JH, Lee HJ, Lee WH, Kang TC, Won MH: Chronological alterations of $P2X_{3}$ receptor expression in the trigeminal ganglion after ischaemic insult in the Mongolian gerbil. Anat Histol Embryol 33 : 220-224, 2004 https://doi.org/10.1111/j.1439-0264.2004.00540.x
  19. Hwang SJ, Valtschanoff JG: Vanilloid receptor VR1-positive afferents are distributed differently at different levels of the rat lumbar spinal cord. Neurosci Lett 349 : 41-44, 2003 https://doi.org/10.1016/S0304-3940(03)00750-X
  20. Ichikawa H, Sugimoto T: VR1-immunoreactive primary sensory neurons in the rat trigeminal ganglion. Brain Res 890 : 184-188, 2001 https://doi.org/10.1016/S0006-8993(00)03253-4
  21. Jiang J, Gu J: Expression of adenosine triphosphate $P2X_{3}$ receptors in rat molar pulp and trigeminal ganglia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 94 : 622-626, 2002 https://doi.org/10.1067/moe.2002.128973
  22. Kanjhan R, Housley GD, Burton LD, Christie DL, Kippenberger A, Thorne PR, Luo L, Ryan AF: Distribution of the $P2X_{2}$ receptor subunit of the ATP-gated ion channels in the rat central nervous system. J Comp Neurol 407 : 11-32, 1999 https://doi.org/10.1002/(SICI)1096-9861(19990428)407:1<11::AID-CNE2>3.0.CO;2-R
  23. Khakh BS, Henderson G: ATP receptor-mediated enhancement of fast excitatory neurotransmitter release in the brain. Mol Pharmacol 54 : 372-378, 1998 https://doi.org/10.1124/mol.54.2.372
  24. Kim YS, Paik SK, Cho YS, Shin HS, Bae JY, Moritani M, Yoshida A, Ahn DK, Valtschanoff J, Hwang SJ, Moon C, Bae YC: Expression of $P2X_{3}$ receptor in the trigeminal sensory nuclei of the rat. J Comp Neurol 506 : 627-39, 2008 https://doi.org/10.1002/cne.21544
  25. Le KT, Villeneuve P, Ramjaun AR, McPherson PS, Beaudet A, Seguela P: Sensory presynaptic and widespread somatodendritic immunolocalization of central ionotropic P2X ATP receptors. Neuroscience 83 : 177-190, 1998 https://doi.org/10.1016/S0306-4522(97)00365-5
  26. Li P, Calejesan AA, Zhuo M: ATP P2X receptors and sensory synaptic transmission between primary afferent fibers and spinal dorsal horn neurons in rats. J Neurophysiol 80 : 3356-3360, 1998 https://doi.org/10.1152/jn.1998.80.6.3356
  27. Llewellyn-Smith IJ, Burnstock G: Ultrastructural localization of $P2X_{3}$ receptors in rat sensory neurons. Neuroreport 9 : 2545-2550, 1998 https://doi.org/10.1097/00001756-199808030-00022
  28. Loesch A, Burnstock G: Electron-immunocytochemical localization of $P2X_{1}$ receptors in the rat cerebellum. Cell Tissue Res 294 : 253-260, 1998 https://doi.org/10.1007/s004410051175
  29. Maehara Y, Kusumoto H, Anai H, Kusumoto T, Sugimachi K: Human tumor tissues have higher ATP contents than normal tissues. Clin Chim Acta 169 : 341-343, 1987 https://doi.org/10.1016/0009-8981(87)90337-8
  30. Michael GJ, Priestley JV: Differential expression of the mRNA for the vanilloid receptor subtype 1 in cells of the adult rat dorsal root and nodose ganglia and its downregulation by axotomy. J Neurosci 19 : 1844-1854. 1999 https://doi.org/10.1523/JNEUROSCI.19-05-01844.1999
  31. Novakovic SD, Kassotakis LC, Oglesby IB, Smith JA, Eglen RM, Ford AP, Hunter JC: Immunocytochemical localization of $P2X_{3}$ purinoceptors in sensory neurons in naive rats and following neuropathic injury. Pain 80 : 273-282, 1999 https://doi.org/10.1016/S0304-3959(98)00225-5
  32. Olszewski J: On the anatomical and functional organization of the spinal trigeminal nucleus. J Comp Neurol 92 : 401-413, 1950 https://doi.org/10.1002/cne.900920305
  33. Siems WG, Grune T, Schmidt H, Tikhonov YV, Pimenov AM: Purine nucleotide levels in host tissues of Ehrlich ascites tumor-bearing mice in different growth phases of the tumor. Cancer Res 53 : 5143-5147, 1993
  34. Sikand P, Premkumar LS: Potentiation of glutamatergic synaptic transmission by protein kinase C-mediated sensitization of TRPV1 at the first sensory synapse. J Physiol 581(Pt 2) : 631-647, 2007 https://doi.org/10.1113/jphysiol.2006.118620
  35. Souslova V, Cesare P, Ding Y, Akopian AN, Stanfa L, Suzuki R, Carpenter K, Dickenson A, Boyce S, Hill R, Nebenuis-Oosthuizen D, Smith AJ, Kidd EJ, Wood JN: Warm-coding deficits and aberrant inflammatory pain in mice lacking $P2X_{3}$ receptors. Nature 407 : 1015-1017, 2000 https://doi.org/10.1038/35039526
  36. Szallasi A, Blumberg PM: Vanilloid (Capsaicin) receptors and mechanisms. Pharmacol Rev 51 : 159-212, 1999
  37. Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D: The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 21 : 531-543, 1998 https://doi.org/10.1016/S0896-6273(00)80564-4
  38. Tsuda M, Ueno S, Inoue K: In vivo pathway of thermal hyperalgesia by intrathecal administration of alpha,beta-methylene ATP in mouse spinal cord: involvement of the glutamate-NMDA receptor system. Br J Pharmacol 127 : 449-456, 1999a https://doi.org/10.1038/sj.bjp.0702582
  39. Tsuda M, Ueno S, Inoue K: Evidence for the involvement of spinal endogenous ATP and P2X receptors in nociceptive responses caused by formalin and capsaicin in mice. Br J Pharmacol 128 : 1497-1504, 1999b https://doi.org/10.1038/sj.bjp.0702960
  40. Valtschanoff JG, Rustioni A, Guo A, Hwang SJ: Vanilloid receptor VR1 is both presynaptic and postsynaptic in the superficial laminae of the rat dorsal horn. J Comp Neurol 436 : 225-235, 2001 https://doi.org/10.1002/cne.1063
  41. Vulchanova L, Riedl MS, Shuster SJ, Buell G, Surprenant A, North RA, Elde R: Immunohistochemical study of the $P2X_{2}$ and $P2X_{3}$ receptor subunits in rat and monkey sensory neurons and their central terminals. Neuropharmacology 36 : 1229-1242, 1997 https://doi.org/10.1016/S0028-3908(97)00126-3
  42. Vulchanova L, Riedl MS, Shuster SJ, Stone LS, Hargreaves KM, Buell G, Surprenant A, North RA, Elde R: $P2X_{3}$ is expressed by DRG neurons that terminate in inner lamina II. Eur J Neurosci 10 : 3470-3478, 1998 https://doi.org/10.1046/j.1460-9568.1998.00355.x
  43. Xiang Z, Bo X, Burnstock G: Localization of ATP-gated P2X receptor immunoreactivity in rat sensory and sympathetic ganglia. Neurosci Lett 256 : 105-108, 1998 https://doi.org/10.1016/S0304-3940(98)00774-5