International Journal of Oral Biology

The Korean Academy of Oral Biology (대한구강생물학회)
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Botulinum Toxin Type A Attenuates Activation of Glial Cells in Rat Medullary Dorsal Horn with CFA-induced Inflammatory Pain

  • Kim, Min-Ji (Department of Oral Physiology, School of Dentistry, Kyungpook National University) ;
  • Cho, Jin-Ho (Department of Oral Physiology, School of Dentistry, Kyungpook National University) ;
  • Kim, Hye-Jin (Department of Oral Physiology, School of Dentistry, Kyungpook National University) ;
  • Yang, Kui-Ye (Department of Oral Physiology, School of Dentistry, Kyungpook National University) ;
  • Ju, Jin-Sook (Department of Oral Physiology, School of Dentistry, Kyungpook National University) ;
  • Lee, Min-Kyung (Department of Dental Hygiene, Dong-Eui University) ;
  • Park, Min-Kyoung (Department of Dental Hygiene, Kyung-Woon University) ;
  • Ahn, Dong-Kuk (Department of Oral Physiology, School of Dentistry, Kyungpook National University)
  • Received : 2015.03.22
  • Accepted : 2015.06.10
  • Published : 2015.06.30
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Abstract

The activation of glial cells in the spinal cord has been contribute to the initiation and maintenance of pain facilitation induced by peripheral inflammation and nerve injury. The present study investigated effects of botulinum toxin type A (BoNT-A), injected subcutaneously or intracisternally, on the expression of microglia and astrocytes in rats. Complete Freund's Adjuvant (CFA)-induced inflammation was employed as an orofacial chronic inflammatory pain model. A subcutaneous injection of $40{\mu}L$ CFA into the vibrissa pad was performed under 3% isoflurane anesthesia in SD rats. Immunohistochemical analysis for changes in Iba1 (a microglia marker) and GFAP (an astrocyte marker), were performed 5 days after CFA injection. Subcutaneous injection of CFA produced increases in Iba1 and GFAP expression, in the ipsilateral superficial lamia I and II in the medullary dorsal horn of rats. Subcutaneous treatment with BoNT-A attenuated the up-regulation of Iba1 and GFAP expressions induced by CFA injection. Moreover, intracisternal injection of BoNT-A also attenuated the up-regulated Iba1 and GFAP expressions. These results suggest that the anti-nociceptive action of BoNT-A is mediated by modulation activation of glial cells, including microglia and astrocyte.

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References

  1. Ahnert-Hilger G, Bigalke H. Molecular aspects of tetanus and botulinum neurotoxin poisoning. Prog Neurobiol. 1995;46:83-96. https://doi.org/10.1016/0301-0082(95)00003-E
  2. Traba Lopez A, Esteban A. Botulinum toxin in motor disorders: practical considerations with emphasis on interventional neurophysiology. Neurophysiol Clin. 2001; 31:220-229. https://doi.org/10.1016/S0987-7053(01)00263-5
  3. Mense S. Neurobiological basis for the use of botulinum toxin in pain therapy. J Neurol. 2004;251:I1-7.
  4. Rollnik JD, Tanneberger O, Schubert M, Schneider U, Dengler R. Treatment of tension-type headache with botulinum toxin type A: a double-blind, placebo-controlled study. Headache. 2000;40:300-305. https://doi.org/10.1046/j.1526-4610.2000.00044.x
  5. Foster L, Clapp L, Erickson M, Jabbari B. Botulinum toxin A and chronic low back pain: a randomized, double-blind study. Neurology. 2001;56:1290-1293. https://doi.org/10.1212/WNL.56.10.1290
  6. Sheean G. Botulinum toxin for the treatment of musculoskeletal pain and spasm. Curr Pain Headache Rep. 2002;6:460-469. https://doi.org/10.1007/s11916-002-0065-y
  7. Silberstein S, Mathew N, Saper J, Jenkins S. Botulinum toxin type A as a migraine preventive treatment. For the BOTOX Migraine Clinical Research Group. Headache. 2000;40: 445-450. https://doi.org/10.1046/j.1526-4610.2000.00066.x
  8. Smuts JA, Schultz D, Barnard A. Mechanism of action of botulinum toxin type A in migraine prevention: a pilot study. Headache 2004;44:801-805. https://doi.org/10.1111/j.1526-4610.2004.04148.x
  9. Gobel H, Heinze A, Heinze-Kuhn K, Austermann K. Botulinum toxin A in the treatment of headache syndromes and pericranial pain syndromes. Pain. 2001;91:195-199. https://doi.org/10.1016/S0304-3959(01)00292-5
  10. Bach-Rojecky L, Lackovic Z. Antinociceptive effect of botulinum toxin type a in rat model of carrageenan and capsaicin induced pain. Croat Med J. 2005;46:201-208.
  11. Cui M, Khanijou S, Rubino J, Aoki KR. Subcutaneous administration of botulinum toxin A reduces formalininduced pain. Pain. 2004;107:125-133. https://doi.org/10.1016/j.pain.2003.10.008
  12. Welch MJ, Purkiss JR, Foster KA. Sensitivity of embryonic rat dorsal root ganglia neurons to Clostridium botulinum neurotoxins. Toxicon. 2000;38:245-258. https://doi.org/10.1016/S0041-0101(99)00153-1
  13. Lee WH, Shin TJ, Kim HJ, Lee JK, Suh HW, Lee SC, Seo K. Intrathecal administration of botulinum neurotoxin type A attenuates formalin-induced nociceptive responses in mice. Anesth Analg. 2011;112:228-235. doi: 10.1213/ANE.0b013e3181ffa1d7.
  14. Luvisetto S, Marinelli S, Lucchetti F, Marchi F, Cobianchi S, Rossetto O, Montecucco C, Pavone F. Botulinum neurotoxins and formalin-induced pain: central vs. peripheral effects in mice. Brain Res. 2006;1082:124-131. https://doi.org/10.1016/j.brainres.2006.01.117
  15. Bach-Rojecky L, Salkovic-Petrisic M, Lackovic Z. Botulinum toxin type A reduces pain supersensitivity in experimental diabetic neuropathy: bilateral effect after unilateral injection. Eur J Pharmacol. 2010;633:10-14. doi: 10.1016/j.ejphar.2010.01.020.
  16. Bach-Rojecky L, Lackovic Z. Central origin of the antinociceptive action of botulinum toxin type A. Pharmacol Biochem Behav. 2009;94:234-238. doi: 10.1016/j.pbb.2009.08.012.
  17. Lee GW. Peripheral and central administration of botulinium toxin type A attenuated orofacial pain in rats. Thesis for master degree, 2013.
  18. Kitamura Y, Matsuka Y, Spigelman I, Ishihara Y, Yamamoto Y, Sonoyama W, Kamioka H, Yamashiro T, Kuboki T, Oguma K. Botulinum toxin type a (150 kDa) decreases exaggerated neurotransmitter release from trigeminal ganglion neurons and relieves neuropathy behaviors induced by infraorbital nerve constriction. Neuroscience. 2009;159:1422-1429. doi: 10.1016/j.neuroscience.2009.01.066.
  19. Durham PL, Cady R, Cady R. Regulation of calcitonin gene-related peptide secretion from trigeminal nerve cells by botulinum toxin type A: implications for migraine therapy. Headache. 2004;44:35-42. https://doi.org/10.1111/j.1526-4610.2004.04007.x
  20. Meng J, Wang J, Lawrence G, Dolly JO. Synaptobrevin I mediates exocytosis of CGRP from sensory neurons and inhibition by botulinum toxins reflects their anti-nociceptive potential. J Cell Sci. 2007;120:2864-2874. https://doi.org/10.1242/jcs.012211
  21. Gazerani P, Staahl C, Drewes AM, Arendt-Nielsen L. The effects of Botulinum Toxin type A on capsaicin-evoked pain, flare, and secondary hyperalgesia in an experimental human model of trigeminal sensitization. Pain. 2006;122:315-325. https://doi.org/10.1016/j.pain.2006.04.014
  22. Borodic GE, Acquadro MA. The use of botulinum toxin for the treatment of chronic facial pain. J Pain. 2002;3:21-27. https://doi.org/10.1054/jpai.2002.27142
  23. Guo W, Wang H, Watanabe M, Shimizu K, Zou S, LaGraize SC, Wei F, Dubner R, Ren K. Glial-cytokine-neuronal interactions underlying the mechanisms of persistent pain. J Neurosci. 2007;27:6006-6018. https://doi.org/10.1523/JNEUROSCI.0176-07.2007
  24. Ren K, Dubner R. Interactions between the immune and nervous systems in pain. Nat Med. 2010;16:1267-1276. https://doi.org/10.1038/nm.2234
  25. Xie YF, Zhang S, Chiang CY, Hu JW, Dostrovsky JO, Sessle BJ. Involvement of glia in central sensitization in trigeminal subnucleus caudalis (medullary dorsal horn). Brain Behav Immun. 2007;21:634-641. https://doi.org/10.1016/j.bbi.2006.07.008
  26. Ahn DK, Kim YS, Park JS. Central NO is involved in the antinociceptive action of intracisternal antidepressants in freely moving rats. Neurosci Lett. 1998;243:105-108. https://doi.org/10.1016/S0304-3940(98)00099-8
  27. Ahn DK, Chae JM, Choi HS, Kyung HM, Kwon OW, Park HS, Youn DH, Bae YC. Central cyclooxygenase inhibitors reduced IL-1beta-induced hyperalgesia in temporomandibular joint of freely moving rats. Pain. 2005;117:204-213 https://doi.org/10.1016/j.pain.2005.06.009
  28. Wang XM, Zhang ZJ, Bains R, Mokha SS. Effect of antisense knock-down of alpha(2a)-and alpha(2c)-adrenoceptors on the antinociceptive action of clonidine on trigeminal nociception in the rat. Pain. 2002;98:27-35. https://doi.org/10.1016/S0304-3959(01)00464-X
  29. Yaksh TL, Rudy TA. Chronic catheterization of the spinal subarachnoid space. Physiol Behav. 1976;17:1031-1036. https://doi.org/10.1016/0031-9384(76)90029-9
  30. Park MK, Song HC, Yang KY, Ju JS, Ahn DK. Participation of peripheral P2X receptors in orofacial inflammatory nociception in rats. Int J Oral Biol. 2011;36:143-148.
  31. Han SR, Yeo SP, Lee MK, Bae YC, Ahn DK. Early dexamethasone relieves trigeminal neuropathic pain. J Dent Res. 2010;89:915-920. doi: 10.1177/0022034510374056.
  32. Park CK, Kim K, Jung SJ, Kim MJ, Ahn DK, Hong SD, Kim JS, Oh SB. Molecular mechanism for local anesthetic action of eugenol in the rat trigeminal system. Pain. 2009;144:84-94. https://doi.org/10.1016/j.pain.2009.03.016
  33. Rizo J, Sudhof TC. Mechanics of membrane fusion. Nat Struct Biol. 1998;5:839-842. https://doi.org/10.1038/2280
  34. Kim HJ, Lee GW, Kim MJ, Yang KY, Kim ST, Bae YC, Ahn DK. Antinociceptive effects of transcytosed botulinum neurotoxin type A on trigeminal nociception in rats. KJPP. 2015, in press.
  35. Kreutzberg GW. Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 1996;19:312-318. https://doi.org/10.1016/0166-2236(96)10049-7
  36. Inoue K, Tsuda M. Purinergic systems, neuropathic pain and the role of microglia. Exp Neurol. 2012;234:293-301. doi: 10.1016/j.expneurol.2011.09.016.
  37. Tsuda M, Tozaki-Saitoh H, Inoue K. Purinergic system, microglia and neuropathic pain. Curr Opin Pharmacol. 2012;12:74-79. doi: 10.1016/j.coph.2011.10.014.
  38. Garrison CJ, Dougherty PM, Kajander KC, Carlton SM. Staining of glial fibrillary acidic protein (GFAP) in lumbar spinal cord increases following a sciatic nerve constriction injury. Brain Res. 1991;565:1-7. https://doi.org/10.1016/0006-8993(91)91729-K
  39. Didier M, Harandi M, Aguera M, Bancel B, Tardy M, Fages C, Calas A, Stagaard M, Mollgard K, Belin MF. Differential immunocytochemical staining for glial fibrillary acidic (GFA) protein, S-100 protein and glutamine synthetase in the rat subcommissural organ, nonspecialized ventricular ependyma and adjacent neuropil. Cell Tissue Res. 1986;245:343-351.
  40. Sweitzer SM, Colburn RW, Rutkowski M, DeLeo JA. Acute peripheral inflammation induces moderate glial activation and spinal IL-1beta expression that correlates with pain behavior in the rat. Brain Res. 1999;829:209-221. https://doi.org/10.1016/S0006-8993(99)01326-8
  41. Colburn RW, Rickman AJ, DeLeo JA. The effect of site and type of nerve injury on spinal glial activation and neuropathic pain behavior. Exp Neurol. 1999;157:289-304. https://doi.org/10.1006/exnr.1999.7065
  42. Zhuang ZY, Wen YR, Zhang DR, Borsello T, Bonny C, Strichartz GR, Decosterd I, Ji RR. A peptide c-Jun N-terminal kinase (JNK) inhibitor blocks mechanical allodynia after spinal nerve ligation: respective roles of JNK activation in primary sensory neurons and spinal astrocytes for neuropathic pain development and maintenance. J Neurosci. 2006;26:3551-3560. https://doi.org/10.1523/JNEUROSCI.5290-05.2006
  43. Dieb W, Hafidi A. Astrocytes are involved in trigeminal dynamic mechanical allodynia: potential role of D-serine. J Dent Res. 2013;92:808-813. doi: 10.1177/0022034513498898.
  44. Lee S, Zhao YQ, Ribeiro-da-Silva A, Zhang J. Distinctive response of CNS glial cells in oro-facial pain associated with injury, infection and inflammation. Mol Pain. 2010;6:79. doi:10.1186/1744-8069-6-79.
  45. Lindia JA, McGowan E, Jochnowitz N, Abbadie C. Induction of CX3CL1 expression in astrocytes and CX3CR1 in microglia in the spinal cord of a rat model of neuropathic pain. J Pain. 2005;6:434-438. https://doi.org/10.1016/j.jpain.2005.02.001
  46. Raghavendra V, Tanga FY, DeLeo JA. Complete Freunds adjuvant-induced peripheral inflammation evokes glial activation and proinflammatory cytokine expression in the CNS. Eur J Neurosci. 2004;20:467-473. https://doi.org/10.1111/j.1460-9568.2004.03514.x
  47. Hua Y, Scheller RH. Three SNARE complexes cooperate to mediate membrane fusion. Proc Natl Acad Sci U S A. 2001;98:8065-8070. https://doi.org/10.1073/pnas.131214798
  48. Sudhof TC. The synaptic vesicle cycle revisited. Neuron. 2000;28:317-320. https://doi.org/10.1016/S0896-6273(00)00109-4
  49. Keller JE, Neale EA. The role of the synaptic protein snap-25 in the potency of botulinum neurotoxin type A. J Biol Chem. 2001;276:13476-13482. https://doi.org/10.1074/jbc.M010992200
  50. Schiavo G, Matteoli M, Montecucco C. Neurotoxins affecting neuroexocytosis. Physiol Rev. 2000;80:717-766. https://doi.org/10.1152/physrev.2000.80.2.717
  51. Matak I, Bach-Rojecky L, Filipovic B, Lackovic Z. Behavioral and immunohistochemical evidence for central antinociceptive activity of botulinum toxin A. Neuroscience. 2011;186:201-207. doi: 10.1016/j.neuroscience.2011.04.026.
  52. Marinelli S, Luvisetto S, Cobianchi S, Makuch W, Obara I, Mezzaroma E, Caruso M, Straface E, Przewlocka B, Pavone F. Botulinum neurotoxin type A counteracts neuropathic pain and facilitates functional recovery after peripheral nerve injury in animal models. Neuroscience. 2010;171:316-328. doi: 10.1016/j.neuroscience.2010.08.067.
  53. DeLeo JA, Yezierski RP. The role of neuroinflammation and neuroimmune activation in persistent pain. Pain. 2001;90:1-6. https://doi.org/10.1016/S0304-3959(00)00490-5
  54. Marchand F, Perretti M, McMahon SB. Role of the immune system in chronic pain. Nat Rev Neurosci. 2005;6:521-532.
  55. Watkins LR, Milligan ED, Maier SF. Glial activation: a driving force for pathological pain. Trends Neurosci. 2001;24:450-455. https://doi.org/10.1016/S0166-2236(00)01854-3
  56. Wieseler-Frank J, Maier SF, Watkins LR. Glial activation and pathological pain. Neurochem Int. 2004;45:389-395. https://doi.org/10.1016/j.neuint.2003.09.009