The Korean Journal of Pain

The Korean Pain Society (대한통증학회)
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The ability of orexin-A to modify pain-induced cyclooxygenase-2 and brain-derived neurotrophic factor expression is associated with its ability to inhibit capsaicin-induced pulpal nociception in rats

  • Shahsavari, Fatemeh (Department of Biology, Faculty of Sciences, Shahid Bahonar University) ;
  • Abbasnejad, Mehdi (Department of Biology, Faculty of Sciences, Shahid Bahonar University) ;
  • Esmaeili-Mahani, Saeed (Department of Biology, Faculty of Sciences, Shahid Bahonar University) ;
  • Raoof, Maryam (Academisch Centrum Tandheelkunde Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam)
  • Received : 2022.02.03
  • Accepted : 2022.04.08
  • Published : 2022.07.01
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Abstract

Background: The rostral ventromedial medulla (RVM) is a critical region for the management of nociception. The RVM is also involved in learning and memory processes due to its relationship with the hippocampus. The purpose of the present study was to investigate the molecular mechanisms behind orexin-A signaling in the RVM and hippocampus's effects on capsaicin-induced pulpal nociception and cognitive impairments in rats. Methods: Capsaicin (100 g) was applied intradentally to male Wistar rats to induce inflammatory pulpal nociception. Orexin-A and an orexin-1 receptor antagonist (SB-334867) were then microinjected into the RVM. Immunoblotting and immunofluorescence staining were used to check the levels of cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) in the RVM and hippocampus. Results: Interdental capsaicin treatment resulted in nociceptive responses as well as a reduction in spatial learning and memory. Additionally, it resulted in decreased BDNF and increased COX-2 expression levels. Orexin-A administration (50 pmol/1 µL/rat) could reverse such molecular changes. SB-334867 microinjection (80 nM/1 µL/rat) suppressed orexin's effects. Conclusions: Orexin-A signaling in the RVM and hippocampus modulates capsaicin-induced pulpal nociception in male rats by increasing BDNF expression and decreasing COX-2 expression.

Keywords

Acknowledgement

The authors wish to express their appreciation for the financial support provided by the Kerman Neuroscience Research Center. This study was granted by Kerman University of Medical Sciences (grant number: 11-96).

References

  1. Takemura M, Sugiyo S, Moritani M, Kobayashi M, Yonehara N. Mechanisms of orofacial pain control in the central nervous system. Arch Histol Cytol 2006; 69: 79-100. https://doi.org/10.1679/aohc.69.79
  2. Heinricher MM, Tavares I, Leith JL, Lumb BM. Descending control of nociception: specificity, recruitment and plasticity. Brain Res Rev 2009; 60: 214-25. https://doi.org/10.1016/j.brainresrev.2008.12.009
  3. Porreca F, Ossipov MH, Gebhart GF. Chronic pain and medullary descending facilitation. Trends Neurosci 2002; 25: 319-25. https://doi.org/10.1016/S0166-2236(02)02157-4
  4. Liu MG, Chen J. Roles of the hippocampal formation in pain information processing. Neurosci Bull 2009; 25: 237-66. https://doi.org/10.1007/s12264-009-0905-4
  5. Voisin T, Rouet-Benzineb P, Reuter N, Laburthe M. Orexins and their receptors: structural aspects and role in peripheral tissues. Cell Mol Life Sci 2003; 60: 72-87. https://doi.org/10.1007/s000180300005
  6. DiMicco JA, Samuels BC, Zaretskaia MV, Zaretsky DV. The dorsomedial hypothalamus and the response to stress: part renaissance, part revolution. Pharmacol Biochem Behav 2002; 71: 469-80. https://doi.org/10.1016/S0091-3057(01)00689-X
  7. Lungwitz EA, Molosh A, Johnson PL, Harvey BP, Dirks RC, Dietrich A, et al. Orexin-A induces anxiety-like behavior through interactions with glutamatergic receptors in the bed nucleus of the stria terminalis of rats. Physiol Behav 2012; 107: 726-32. https://doi.org/10.1016/j.physbeh.2012.05.019
  8. Yeoh JW, Campbell EJ, James MH, Graham BA, Dayas CV. Orexin antagonists for neuropsychiatric disease: progress and potential pitfalls. Front Neurosci 2014; 8: 36. https://doi.org/10.3389/fnins.2014.00036
  9. Darwinkel A, Stanic D, Booth LC, May CN, Lawrence AJ, Yao ST. Distribution of orexin-1 receptor-green fluorescent protein- (OX1-GFP) expressing neurons in the mouse brain stem and pons: co-localization with tyrosine hydroxylase and neuronal nitric oxide synthase. Neuroscience 2014; 278: 253-64. https://doi.org/10.1016/j.neuroscience.2014.08.027
  10. Raoof M, Esmaeili-Mahani S, Nourzadeh M, Raoof R, Abbasnejad M, Amirkhosravi L, et al. Noxious stimulation of the rat tooth pulp may impair learning and memory through the induction of hippocampal apoptosis. J Oral Facial Pain Headache 2015; 29: 390-7. https://doi.org/10.11607/ofph.1452
  11. Chuang YC, Yoshimura N, Huang CC, Wu M, Chiang PH, Chancellor MB. Intraprostatic botulinum toxin a injection inhibits cyclooxygenase-2 expression and suppresses prostatic pain on capsaicin induced prostatitis model in rat. J Urol 2008; 180: 742-8. https://doi.org/10.1016/j.juro.2007.07.120
  12. 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; 19: 3375-81. https://doi.org/10.1111/j.0953-816X.2004.03441.x
  13. Rahbar I, Abbasnejad M, Haghani J, Raoof M, Kooshki R, Esmaeili-Mahani S. The effect of central administration of alpha-pinene on capsaicin-induced dental pulp nociception. Int Endod J 2019; 52: 307-17. https://doi.org/10.1111/iej.13006
  14. Merighi A, Salio C, Ghirri A, Lossi L, Ferrini F, Betelli C, et al. BDNF as a pain modulator. Prog Neurobiol 2008; 85: 297-317. https://doi.org/10.1016/j.pneurobio.2008.04.004
  15. Pezet S, Malcangio M, McMahon SB. BDNF: a neuromodulator in nociceptive pathways? Brain Res Brain Res Rev 2002; 40: 240-9. https://doi.org/10.1016/S0165-0173(02)00206-0
  16. Bekinschtein P, Cammarota M, Medina JH. BDNF and memory processing. Neuropharmacology 2014; 76 Pt C: 677-83. https://doi.org/10.1016/j.neuropharm.2013.04.024
  17. Webster MJ, Herman MM, Kleinman JE, Shannon Weickert C. BDNF and trkB mRNA expression in the hippocampus and temporal cortex during the human lifespan. Gene Expr Patterns 2006; 6: 941-51. https://doi.org/10.1016/j.modgep.2006.03.009
  18. Raoof M, Ashrafganjoui E, Kooshk i R, Abbasnejad M, Haghani J, Amanpour S, et al. Effect of chronic stress on capsaicin-induced dental nociception in a model of pulpitis in rats. Arch Oral Biol 2018; 85: 154-9. https://doi.org/10.1016/j.archoralbio.2017.10.012
  19. Lucas SM, Rothwell NJ, Gibson RM. The role of inflammation in CNS injury and disease. Br J Pharmacol 2006; 147(Suppl 1): S232-40. https://doi.org/10.1038/sj.bjp.0706400
  20. Inada M, Matsumoto C, Uematsu S, Akira S, Miyaura C. Membrane-bound prostaglandin E synthase-1-mediated prostaglandin E2 production by osteoblast plays a critical role in lipopolysaccharide-induced bone loss associated with inflammation. J Immunol 2006; 177: 1879-85. https://doi.org/10.4049/jimmunol.177.3.1879
  21. Kooshki R, Abbasnejad M, Esmaeili Mahani S, Raoof M, Moeini Aghtaei MM, Dabiri S. Orexin-A inhibits capsaicin-induced changes in cyclooxygenase-2 and brain-derived neurotrophic factor expression in trigeminal nucleus caudalis of rats. Korean J Pain 2018; 31: 174-82. https://doi.org/10.3344/kjp.2018.31.3.174
  22. Ahn DK, Choi HS, Yeo SP, Woo YW, Lee MK, Yang GY, et al. Blockade of central cyclooxygenase (COX) pathways enhances the cannabinoid-induced antinociceptive effects on inflammatory temporomandibular joint (TMJ) nociception. Pain 2007; 132: 23-32. https://doi.org/10.1016/j.pain.2007.01.015
  23. Neeb L, Hellen P, Boehnke C, Hoffmann J, Schuh-Hofer S, Dirnagl U, et al. IL-1β stimulates COX-2 dependent PGE2 synthesis and CGRP release in rat trigeminal ganglia cells. PLoS One 2011; 6: e1736.
  24. Zhou Y, Long H, Ye N, Liao L, Yang X, Jian F, et al. The effect of capsaicin on expression patterns of CGRP in trigeminal ganglion and trigeminal nucleus caudalis following experimental tooth movement in rats. J Appl Oral Sci 2016; 24: 597-606. https://doi.org/10.1590/1678-775720160150
  25. Hay C, de Belleroche J. Carrageenan-induced hyperalgesia is associated with increased cyclo-oxygenase-2 expression in spinal cord. Neuroreport 1997; 8: 1249-51. https://doi.org/10.1097/00001756-199703240-00038
  26. Carlson JD, Maire JJ, Martenson ME, Heinricher MM. Sensitization of pain-modulating neurons in the rostral ventromedial medulla after peripheral nerve injury. J Neurosci 2007; 27: 13222-31. https://doi.org/10.1523/JNEUROSCI.3715-07.2007
  27. Sanoja R, Tortorici V, Fernandez C, Price TJ, Cervero F. Role of RVM neurons in capsaicin-evoked visceral nociception and referred hyperalgesia. Eur J Pain 2010; 14: 120.e1-9.
  28. 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; 157: 20-7. https://doi.org/10.1016/j.physbeh.2016.01.031
  29. Azhdari-Zarmehri H, Semnanian S, Fathollahi Y, Pakdel FG. Tail flick modification of orexin-a induced changes of electrophysiological parameters in the rostral ventromedial medulla. Cell J 2014; 16: 131-40.
  30. Ogawa Y, Irukayama-Tomobe Y, Murakoshi N, Kiyama M, Ishikawa Y, Hosokawa N, et al. Peripherally administered orexin improves survival of mice with endotoxin shock. Elife 2016; 5: e21055. https://doi.org/10.7554/elife.21055
  31. Messal N, Fernandez N, Dayot S, Gratio V, Nicole P, Prochasson C, et al. Ectopic expression of OX1R in ulcerative colitis mediates anti-inflammatory effect of orexin-A. Biochim Biophys Acta Mol Basis Dis 2018; 1864: 3618-28. https://doi.org/10.1016/j.bbadis.2018.08.023
  32. Becquet L, Abad C, Leclercq M, Miel C, Jean L, Riou G, et al. Systemic administration of orexin A ameliorates established experimental autoimmune encephalomyelitis by diminishing neuroinflammation. J Neuroinflammation 2019; 16: 64. https://doi.org/10.1186/s12974-019-1447-y
  33. 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; 50: 9-16. https://doi.org/10.1016/j.npep.2015.03.002
  34. Buldyrev I, Tanner NM, Hsieh HY, Dodd EG, Nguyen LT, Balkowiec A. Calcitonin gene-related peptide enhances release of native brain-derived neurotrophic factor from trigeminal ganglion neurons. J Neurochem 2006; 99: 1338-50. https://doi.org/10.1111/j.1471-4159.2006.04161.x
  35. Trang T, Beggs S, Salter MW. Brain-derived neurotrophic factor from microglia: a molecular substrate for neuropathic pain. Neuron Glia Biol 2011; 7: 99-108. https://doi.org/10.1017/S1740925X12000087
  36. Latremoliere A, Woolf CJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain 2009; 10: 895-926. https://doi.org/10.1016/j.jpain.2009.06.012
  37. Duric V, McCarson KE. Persistent pain produces stress-like alterations in hippocampal neurogenesis and gene expression. J Pain 2006; 7: 544-55. https://doi.org/10.1016/j.jpain.2006.01.458
  38. Aubdool AA, Kodji X, Abdul-Kader N, Heads R, Fernandes ES, Bevan S, et al. TRPA1 activation leads to neurogenic vasodilatation: involvement of reactive oxygen nitrogen species in addition to CGRP and NO. Br J Pharmacol 2016; 173: 2419-33. https://doi.org/10.1111/bph.13519
  39. Kapczinski F, Frey BN, Andreazza AC, Kauer-Sant'Anna M, Cunha AB, Post RM. Increased oxidative stress as a mechanism for decreased BDNF levels in acute manic episodes. Braz J Psychiatry 2008; 30: 243-5. https://doi.org/10.1590/S1516-44462008000300011
  40. Akbari E, Naghdi N, Motamedi F. The selective orexin 1 receptor antagonist SB-334867-A impairs acquisition and consolidation but not retrieval of spatial memory in Morris water maze. Peptides 2007; 28: 650-6. https://doi.org/10.1016/j.peptides.2006.11.002
  41. Choi YS, Cho HY, Hoyt KR, Naegele JR, Obrietan K. IGF-1 receptor-mediated ERK/MAPK signaling couples status epilepticus to progenitor cell proliferation in the subgranular layer of the dentate gyrus. Glia 2008; 56: 791-800. https://doi.org/10.1002/glia.20653
  42. Lee S, Yang M, Kim J, Son Y, Kim J, Kang S, et al. Involvement of BDNF/ERK signaling in spontaneous recovery from trimethyltin-induced hippocampal neurotoxicity in mice. Brain Res Bull 2016; 121: 48-58. https://doi.org/10.1016/j.brainresbull.2016.01.002
  43. Veyrac A, Gros A, Bruel-Jungerman E, Rochefort C, Kleine Borgmann FB, Jessberger S, et al. Zif268/egr1 gene controls the selection, maturation and functional integration of adult hippocampal newborn neurons by learning. Proc Natl Acad Sci U S A 2013; 110: 7062-7. https://doi.org/10.1073/pnas.1220558110
  44. Meyer-Tuve A, Malcangio M, Ebersberger A, Mazario J, Schaible HG. Effect of brain-derived neurotrophic factor on the release of substance P from rat spinal cord. Neuroreport 2001; 12: 21-4. https://doi.org/10.1097/00001756-200101220-00012
  45. Yang L, Zou B, Xiong X, Pascual C, Xie J, Malik A, et al. Hypocretin/orexin neurons contribute to hippocampus-dependent social memory and synaptic plasticity in mice. J Neurosci 2013; 33: 5275-84. https://doi.org/10.1523/JNEUROSCI.3200-12.2013
  46. Marmigere F, Givalois L, Rage F, Arancibia S, Tapia-Arancibia L. Rapid induction of BDNF expression in the hippocampus during immobilization stress challenge in adult rats. Hippocampus 2003; 13: 646-55. https://doi.org/10.1002/hipo.10109
  47. Wang H, Ye M, Yu L, Wang J, Guo Y, Lei W, et al. Hippocampal neuronal cyclooxygenase-2 downstream signaling imbalance in a rat model of chronic aluminium gluconate administration. Behav Brain Funct 2015; 11: 8. https://doi.org/10.1186/s12993-015-0054-z
  48. 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; 343: 346-54. https://doi.org/10.1016/j.neuroscience.2016.12.016
  49. Kooshki R, Abbasnejad M, Esmaeili-Mahani S, Raoof M. The effect of CA1 administration of orexin-A on hippocampal expression of COX-2 and BDNF in a rat model of orofacial pain. Arq Neuropsiquiatr 2018; 76: 603-8. https://doi.org/10.1590/0004-282x20180099