PDF herunterladen
CC BY-NC-ND 4.0 · Arq Neuropsiquiatr 2018; 76(09): 603-608
DOI: 10.1590/0004-282X20180099
Article

The effect of CA1 administration of orexin-A on hippocampal expression of COX-2 and BDNF in a rat model of orofacial pain

O efeito da administração de CA1 de orexina-A na expressão hipocampal de COX-2 e BDNF em um modelo de dor orofacial em ratos
Razieh Kooshki
1   Shahid Bahonar University of Kerman, Faculty of Sciences, Department of Biology, Kerman, Iran;
,
Mehdi Abbasnejad
1   Shahid Bahonar University of Kerman, Faculty of Sciences, Department of Biology, Kerman, Iran;
,
Saeed Esmaeili-Mahani
1   Shahid Bahonar University of Kerman, Faculty of Sciences, Department of Biology, Kerman, Iran;
,
Maryam Raoof
2   Kerman University of Medical Sciences, Institute of Neuropharmacology, Neuroscience Research Center, Laboratory of Molecular Neuroscience, Kerman, Iran;
3   Kerman University of Medical Sciences, Endodontology Research Center, Kerman, Iran.
› Institutsangaben
› Weitere Informationen
Auch verfügbar auf
   Lizenzen und Reprints

ABSTRACT

The neuropeptide orexin-A and its receptors are widely distributed in both hippocampal circuitry and pain transmission pathways.

Objective: Involvement of the CA1 orexin 1 receptor (OX1R) on the modulation of orofacial pain and pain-induced changes in hippocampal expression of cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) was investigated.

Methods: Orofacial pain was induced by an intra-lip injection of capsaicin (100 μg). Reverse transcription polymerase chain reaction and immunoblot analysis were used to indicate changes in hippocampal BDNF and COX-2 expression, respectively.

Results: Capsaicin induces a significant pain response, which is not affected by either orexin-A or SB-334867-A, an OX1R antagonist. However, an increased expression of COX-2 and decreased expression of BDNF was observed in the hippocampus of animals that received capsaicin or SB-334867-A (80 nM) plus capsaicin. Meanwhile, orexin-A (40 pM) attenuated the effects of capsaicin on the expression of COX-2 and BDNF.

Conclusions: CA1 OX1R activation moderates capsaicin-induced neuronal inflammation and neurotrophic deficiency.

RESUMO

O neuropeptídeo orexina-A e seus receptores estão amplamente distribuídos nos circuitos do hipocampo e nas vias de transmissão da dor.

Objetivo: O envolvimento do receptor de orexina 1 CA1 (OX1R) na modulação da dor orofacial e alterações induzidas pela dor na expressão do hipocampo de ciclooxigenase-2 (COX-2) e fator neurotrófico derivado do cérebro (BDNF) foi investigado.

Métodos: A dor orofacial foi induzida por injeção intra-labial de capsaicina (100 μg). A reação em cadeia da polimerase de transcrição reversa e a análise de imunotransferência foram utilizadas para indicar alterações na expressão de BDNF e COX-2 no hipocampo, respectivamente.

Resultados: A capsaicina induz uma resposta significativa à dor, que não é afetada pela orexina-A ou pelo SB-334867-A, um antagonista do OX1R. No entanto, uma expressão aumentada de COX-2 e uma expressão diminuída de BDNF foi observada no hipocampo de animais que receberam capsaicina ou SB-334867-A (80 nM) mais capsaicina. Enquanto isso, a orexina A (40 pM) atenuou os efeitos da capsaicina na expressão de COX-2 e BDNF.

Conclusões: A ativação de CA1 OX1R modera a inflamação neuronal induzida por capsaicina e a deficiência neurotrófica.

Keywords:

Orofacial pain - orexins - brain-derived neurotrophic factor - cyclooxygenase 2 - rats

Palavras-chave:

Dor facial - orexinas - fator neurotrófico derivado do encéfalo - ciclo-oxigenase 2 - ratos


Publikationsverlauf

Eingereicht: 25. März 2018

Angenommen: 12. Juni 2018

Artikel online veröffentlicht:
22. August 2023

© 2023. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

 

  • References

  • 1 Sessle BJ. Neural mechanisms and pathways in craniofacial pain. Can J Neurol Sci. 1999 Nov;26(1 Suppl 3):S7-11. https://doi.org/10.1017/S0317167100000135
  • 2 Delwel S, Binnekade TT, Perez RS, Hertogh CM, Scherder EJ, Lobbezoo F. Oral health and orofacial pain in older people with dementia: a systematic review with focus on dental hard tissues. Clin Oral Investig. 2017 Jan;21(1):17-32. https://doi.org/10.1007/s00784-016-1934-9
  • 3 Bae YC, Oh JM, Hwang SJ, Shigenaga Y, Valtschanoff JG. Expression of vanilloid receptor TRPV1 in the rat trigeminal sensory nuclei. J Comp Neurol. 2004 Oct;478(1):62-71. https://doi.org/10.1002/cne.20272
  • 4 Eid SR, Crown ED, Moore EL, Liang HA, Choong KC, Dima S et al. HC-030031, a TRPA1 selective antagonist, attenuates inflammatory- and neuropathy-induced mechanical hypersensitivity. Mol Pain. 2008 Oct;4:48. https://doi.org/10.1186/1744-8069-4-48
  • 5 Gao Y, Duan YZ. Increased COX2 in the trigeminal nucleus caudalis is involved in orofacial pain induced by experimental tooth movement. Anat Rec (Hoboken). 2010 Mar;293(3):485-91. https://doi.org/10.1002/ar.21078
  • 6 Lee KM, Kang BS, Lee HL, Son SJ, Hwang SH, Kim DS et al. Spinal NF-kB activation induces COX-2 upregulation and contributes to inflammatory pain hypersensitivity. Eur J Neurosci. 2004 Jun;19(12):3375-81. https://doi.org/10.1111/j.0953-816X.2004.03441.x
  • 7 Gottmann K, Mittmann T, Lessmann V. BDNF signaling in the formation, maturation and plasticity of glutamatergic and GABAergic synapses. Exp Brain Res. 2009 Dec;199(3-4):203-34. https://doi.org/10.1007/s00221-009-1994-z
  • 8 Lu Y, Christian K, Lu B. BDNF: a key regulator for protein synthesis-dependent LTP and long-term memory? Neurobiol Learn Mem. 2008 Mar;89(3):312-23. https://doi.org/10.1016/j.nlm.2007.08.018
  • 9 Nagahara AH, Tuszynski MH. Potential therapeutic uses of BDNF in neurological and psychiatric disorders. Nat Rev Drug Discov. 2011 Mar;10(3):209-19. https://doi.org/10.1038/nrd3366
  • 10 Merighi A, Salio C, Ghirri A, Lossi L, Ferrini F, Betelli C, et al. BDNF as a pain modulator. Prog Neurobiol. 2008 Jul;85(3):297-317. https://doi.org/10.1016/j.pneurobio.2008.04.004
  • 11 Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998;92(4):573-85 https://doi.org/10.1016/S0092-8674(00)80949-6
  • 12 Li J, Hu Z, de Lecea L. The hypocretins/orexins: integrators of multiple physiological functions. Br J Pharmacol. 2014 Jan;171(2):332-50. https://doi.org/10.1111/bph.12415
  • 13 Nambu T, Sakurai T, Mizukami K, Hosoya Y, Yanagisawa M, Goto K. Distribution of orexin neurons in the adult rat brain. Brain Res. 1999 May;827(1-2):243-60. https://doi.org/10.1016/S0006-8993(99)01336-0
  • 14 Marcus JN, Aschkenasi CJ, Lee CE, Chemelli RM, Saper CB, Yanagisawa M et al. Differential expression of orexin receptors 1 and 2 in the rat brain. J Comp Neurol. 2001 Jun;435(1):6-25. https://doi.org/10.1002/cne.1190
  • 15 Aou S, Li XL, Li AJ, Oomura Y, Shiraishi T, Sasaki K et al. Orexin-A (hypocretin-1) impairs Morris water maze performance and CA1-Schaffer collateral long-term potentiation in rats. Neuroscience. 2003;119(4):1221-8. https://doi.org/10.1016/S0306-4522(02)00745-5
  • 16 16. Azhdari Zarmehri H, Semnanian S, Fathollahi Y, Erami E, Khakpay R, Azizi H et al. Intra-periaqueductal gray matter microinjection of orexin-A decreases formalin-induced nociceptive behaviors in adult male rats. J Pain. 2011 Feb;12(2):280-7. https://doi.org/10.1016/j.jpain.2010.09.006
  • 17 Yamamoto T, Nozaki-Taguchi N, Chiba T. Analgesic effect of intrathecally administered orexin-A in the rat formalin test and in the rat hot plate test. Br J Pharmacol. 2002 Sep;137(2):170-6. https://doi.org/10.1038/sj.bjp.0704851
  • 18 Holland PR, Akerman S, Goadsby PJ. Modulation of nociceptive dural input to the trigeminal nucleus caudalis via activation of the orexin 1 receptor in the rat. Eur J Neurosci. 2006 Nov;24(10):2825-33. https://doi.org/10.1111/j.1460-9568.2006.05168.x
  • 19 Kooshki R, Abbasnejad M, Esmaeili-Mahani S, Raoof M. The role of trigeminal nucleus caudalis orexin 1 receptors in orofacial pain transmission and in orofacial pain-induced learning and memory impairment in rats. Physiol Behav. 2016 Apr;157:20-7. https://doi.org/10.1016/j.physbeh.2016.01.031
  • 20 Raoof R, Esmaeili-Mahani S, Abbasnejad M, Raoof M, Sheibani V, Kooshki R et al. Changes in hippocampal orexin 1 receptor expression involved in tooth pain-induced learning and memory impairment in rats. Neuropeptides. 2015 Apr;50:9-16. https://doi.org/10.1016/j.npep.2015.03.002
  • 21 Minghetti L. Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases. J Neuropathol Exp Neurol. 2004 Sep;63(9):901-10. https://doi.org/10.1093/jnen/63.9.901
  • 22 Iwaoka E, Wang S, Matsuyoshi N, Kogure Y, Aoki S, Yamamoto S et al. Evodiamine suppresses capsaicin-induced thermal hyperalgesia through activation and subsequent desensitization of the transient receptor potential V1 channels. J Nat Med. 2016 Jan;70(1):1-7. https://doi.org/10.1007/s11418-015-0929-1
  • 23 Xiong X, White RE, Xu L, Yang L, Sun X, Zou B et al. Mitigation of murine focal cerebral ischemia by the hypocretin/orexin system is associated with reduced inflammation. Stroke. 2013 Mar;44(3):764-70. https://doi.org/10.1161/STROKEAHA.112.681700
  • 24 Kitamura E, Hamada J, Kanazawa N, Yonekura J, Masuda R, Sakai F et al. The effect of orexin-A on the pathological mechanism in the rat focal cerebral ischemia. Neurosci Res. 2010 Oct;68(2):154-7. https://doi.org/10.1016/j.neures.2010.06.010
  • 25 Leszek J, Barreto GE, Gąsiorowski K, Koutsouraki E, Ávila-Rodrigues M, Aliev G. Inflammatory mechanisms and oxidative stress as key factors responsible for progression of neurodegeneration: role of brain innate immune system. CNS Neurol Disord Drug Targets. 2016;15(3):329-36. https://doi.org/10.2174/1871527315666160202125914
  • 26 Akbari E, Motamedi F, Davoodi FG, Noorbakhshnia M, Ghanbarian E. Orexin-1 receptor mediates long-term potentiation in the dentate gyrus area of freely moving rats. Behav Brain Res. 2011 Jan;216(1):375-80. https://doi.org/10.1016/j.bbr.2010.08.017
  • 27 Esmaeili-Mahani S, Vazifekhah S, Pasban-Aliabadi H, Abbasnejad M, Sheibani V. Protective effect of orexin-A on 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y human dopaminergic neuroblastoma cells. Neurochem Int. 2013 Dec;63(8):719-25. https://doi.org/10.1016/j.neuint.2013.09.022
  • 28 Pasban-Aliabadi H, Esmaeili-Mahani S, Abbasnejad M. Orexin-A protects human neuroblastoma SH-SY5Y cells against 6-OHDA-induced neurotoxicity: involvement of PKC and PI3K signaling pathways. Rejuvenation Res. 2017 Apr;20(2):125-33. https://doi.org/10.1089/rej.2016.1836
  • 29 Duric V, McCarson KE. Persistent pain produces stress-like alterations in hippocampal neurogenesis and gene expression. J Pain. 2006 Aug;7(8):544-55. https://doi.org/10.1016/j.jpain.2006.01.458
  • 30 Hu Y, Yang J, Hu Y, Wang Y, Li W. Amitriptyline rather than lornoxicam ameliorates neuropathic pain-induced deficits in abilities of spatial learning and memory. Eur J Anaesthesiol. 2010 Feb;27(2):162-8. https://doi.org/10.1097/EJA.0b013e328331a3d5
  • 31 Zhang L, Ding X, Wu Z, Qian X, An J, Tian M. Trigeminal neuralgia induced by cobra venom leads to cognitive deficits associated with downregulation of CREB/BDNF Pathway. Pain Physician. 2017 Feb;20(2):53-68.
  • 32 Mizuno M, Yamada K, Maekawa N, Saito K, Seishima M, Nabeshima T. CREB phosphorylation as a molecular marker of memory processing in the hippocampus for spatial learning. Behav Brain Res. 2002 Jul;133(2):135-41. https://doi.org/10.1016/S0166-4328(01)00470-3
  • 33 Geng SJ, Liao FF, Dang WH, Ding X, Liu XD, Cai J et al. Contribution of the spinal cord BDNF to the development of neuropathic pain by activation of the NR2B-containing NMDA receptors in rats with spinal nerve ligation. Exp Neurol. 2010 Apr;222(2):256-66. https://doi.org/10.1016/j.expneurol.2010.01.003
  • 34 Ren K, Dubner R. Pain facilitation and activity-dependent plasticity in pain modulatory circuitry: role of BDNF-TrkB signaling and NMDA receptors. Mol Neurobiol. 2007 Jun;35(3):224-35. https://doi.org/10.1007/s12035-007-0028-8
  • 35 Harada S, Yamazaki Y, Tokuyama S. Orexin-A suppresses postischemic glucose intolerance and neuronal damage through hypothalamic brain-derived neurotrophic factor. J Pharmacol Exp Ther. 2013 Jan;344(1):276-85. https://doi.org/10.1124/jpet.112.199604
  • 36 Guo Y, Feng P. OX2R activation induces PKC-mediated ERK and CREB phosphorylation. Exp Cell Res. 2012 Oct;318(16):2004-13. https://doi.org/10.1016/j.yexcr.2012.04.015
  • 37 Park H, Poo MM. Neurotrophin regulation of neural circuit development and function. Nat Rev Neurosci. 2013 Jan;14(1):7-23. https://doi.org/10.1038/nrn3379
  • 38 Liu MG, Chen J. Roles of the hippocampal formation in pain information processing. Neurosci Bull. 2009 Oct;25(5):237-66. https://doi.org/10.1007/s12264-009-0905-4
  • 39 Arrigo A, Mormina E, Calamuneri A, Gaeta M, Marino S, Milardi D et al. Amygdalar and hippocampal connections with brainstem and spinal cord: A diffusion MRI study in human brain. Neuroscience. 2017 Feb;343:346-54. https://doi.org/10.1016/j.neuroscience.2016.12.016
  • 40 Rosa E, Mahendram S, Ke YD, Ittner LM, Ginsberg SD, Fahnestock M. Tau downregulates BDNF expression in animal and cellular models of Alzheimer's disease. Neurobiol Aging. 2016 Dec;48:135-42. https://doi.org/10.1016/j.neurobiolaging.2016.08.020