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Role of the thalamic submedius nucleus histamine H1 and H2 and opioid receptors in modulation of formalin-induced orofacial pain in rats

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Abstract

Histamine and opioid systems are involved in supraspinal modulation of pain. In this study, we investigated the effects of separate and combined microinjections of agonists and antagonists of histamine H1 and H2 and opioid receptors into the thalamic submedius (Sm) nucleus on the formalin-induced orofacial pain. Two guide cannulas were implanted into the right and left sides of the Sm in ketamine- and xylazine-anesthetized rats. Orofacial formalin pain was induced by subcutaneous injection of a diluted formalin solution (50 μl, 1.5 %) into the vibrissa pad. Face rubbing durations were recorded at 3-min blocks for 45 min. Formalin produced a biphasic pain response (first phase: 0–3 min and second phase: 15–33 min). Separate and combined microinjections of histamine H1 and H2 receptor agonists, 2-pyridylethylamine (2-PEA) and dimaprit, respectively, and opioid receptor agonist, morphine, attenuated the second phase of pain. The analgesic effects induced by 2-PEA, dimaprit, and morphine were blocked by prior microinjections of fexofenadine (a histamine H1 receptor antagonist), famotidine (a histamine H2 receptor antagonist), and naloxone (an opioid receptor antagonist), respectively. Naloxone also prevented 2-PEA- and dimaprit-induced antinociception, and the analgesic effect induced by morphine was inhibited by fexofenadine and famotidine. These results showed the involvement of histamine H1 and H2 and opioid receptors in the Sm modulation of orofacial pain. Opioid receptor might be involved in analgesia induced by activation of histamine H1 and H2 receptors and vice versa.

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References

  • Bodnar RJ (2014) Endogenous opiates and behavior: 2013. Peptides 62:67–136, PMID: 25263178

    Article  CAS  PubMed  Google Scholar 

  • Braga PC, Soldavini E, Pecile A, Cibilia V, Netti C (1996) Involvement of H1 receptors in the central antinociceptive effect of histamine: pharmacological dissection by electrophysiological analysis. Experientia 52:60–65, PMID: 8575561

    Article  CAS  PubMed  Google Scholar 

  • Clavelou P, Dallel R, Orliaquest T, Woda A, Raboisson P (1995) The orofacial formalin test in rats: effects of different formalin concentrations. Pain 62:295–301, PMID: 8657429

    Article  CAS  PubMed  Google Scholar 

  • Donatti AF, Araujo RM, Soriano RN, Azevedo LU, Leite-Panissi CA, Branco LG (2014) Role of hydrogen sulfide in the formalin-induced orofacial pain in rats. Eur J Pharmacol 738:49–56, PMID: 24876060

    Article  CAS  PubMed  Google Scholar 

  • Duale C, Sierralta F, Dallel R (2007) Analgesia induced by morphine microinjected into the nucleus raphe magnus: effect on tonic pain. Curr Drug Deliv 4:181–184, PMID: 17627491

    Article  CAS  PubMed  Google Scholar 

  • Erfanparast A, Tamaddonfard E, Farshid AA, Khalilzadeh E (2010) Effect of microinjection of histamine into the dorsal hippocampus on the orofacial formalin-induced pain in rats. Eur J Pharmacol 627:119–123, PMID: 19891965

    Article  CAS  PubMed  Google Scholar 

  • Farzin D, Asghari L, Nowrouzi M (2002) Rodent antinociception following acute treatment with different histamine receptor agonists and antagonists. Pharmacol Biochem Behav 72:751–760, PMID: 12175473

    Article  CAS  PubMed  Google Scholar 

  • Feng J, Jia N, Han LN, Huang FS, Xie YF, Liu J, Tang JS (2008) Microinjection of morphine into thalamic nucleus submedius depresses bee venom‐induced inflammatory pain in the rat. J Pharm Pharmacol 60:1355–1363, PMID: 18812029

    Article  CAS  PubMed  Google Scholar 

  • Gogas KR, Hough LB, Eberle NB, Lyon RA, Glick SD, Ward SJ, Yoang RC, Parsons ME (1989) A role for histamine and H2-receptors in opioid antinociception. J Pharmacol Exp Ther 250:476–484, PMID: 2547933

    CAS  PubMed  Google Scholar 

  • Hamzeh-Gooshchi N, Tamaddonfard E, Farshid AA (2015) Effects of microinjection of histamine into the anterior cingulate cortex on pain-related behaviors induced by formalin in rats. Pharmacol Rep 67:593–599, PMID: 25933974

    Article  PubMed  Google Scholar 

  • Hong Y, Abbott FV (1994) Behavioral effects of intraplantar injection of inflammatory mediators in the rat. Neuroscience 63:827–836, PMID: 7898681

    Article  CAS  PubMed  Google Scholar 

  • Hough LB, Nalwalk JW (1992) Inhibition of morphine antinociception by centrally administered histamine H2 receptor antagonists. Eur J Pharmacol 215:69–74, PMID: 1355443

    Article  CAS  PubMed  Google Scholar 

  • Hough LB, Rice FL (2011) H3 receptors and pain modulation: peripheral, spinal, and brain interactions. J Pharmacol Exp Ther 336:30–37, PMID: 20864501

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jin C, Lintunen M, Panula P (2005) Histamine H1 and H3 receptors in the rat thalamus and their modulation after systemic kainic acid administration. Exp Neurol 194:43–56, PMID: 15899242

    Article  CAS  PubMed  Google Scholar 

  • Kajihara Y, Murakami M, Imagawa T, Otsuguro K, Ito S, Ohta T (2010) Histamine potentiates acid-induced responses mediating transient receptor potential V1 in mouse primary sensory neurons. Neuroscience 166:292–304, PMID: 20006972

    Article  CAS  PubMed  Google Scholar 

  • Kanjhan R (1995) Opioids and pain. Clin Exp Pharmacol Physiol 22:397–403, PMID: 8582088

    Article  CAS  PubMed  Google Scholar 

  • Khalilzadeh E, Tamaddonfard E, Farshid AA, Erfanparast A (2010) Microinjection of histamine into the dentate gyrus produces antinociception in the formalin test in rats. Pharmacol Biochem Behav 97:325–332, PMID: 20826178

    Article  CAS  PubMed  Google Scholar 

  • Lamberti C, Bartolini A, Ghelardini C, Malmberg-Aiello P (1996) Investigation into the role of histamine receptors in rodent antinociception. Pharmacol Biochem Behav 53:567–574, PMID: 8866956

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Yuan B, Tang JS (2007) Effect of stimulation and lesion of the thalamic nucleus submedius on formalin-evoked nociceptive behavior in rats. Sheng Li Xue Bao:[Acta Physiol Sin] 59:777–783, PMID: 18157471

    CAS  Google Scholar 

  • Luccarini P, Henry M, Alvarez P, Gaydier AM, Dallel R (2003) Contribution of neurokinin 1 receptors in the cutaneous orofacial inflammatory pain. Naunyn-Schmiedeberg’s Arc Pharmacol 368:320–323, PMID: 14517596

    Article  CAS  Google Scholar 

  • Malmberg-Aiello P, Lamberti C, Ipponi A, Bartolini A, Schunack W (1998) Evidence for hypernociception induced following histamine H1 receptor activation in rodents. Life Sci 63:463–476, PMID: 9718070

    Article  CAS  PubMed  Google Scholar 

  • Miranda HF, Noriega V, Zepeda RJ, Sierralta F, Prieto JC (2013) Systemic synergism between codeine and morphine in three pain models in mice. Pharmacol Rep 65:80–88, PMID: 23563026

    Article  CAS  PubMed  Google Scholar 

  • Mobarakeh JI, Sakurada S, Katsuyama S, Kutsuwa M, Kuramasu A, Lin ZY, Watanabe T, Hashimoto Y, Watanabe T, Yanai K (2000) Role of histamine H1 receptor in pain perception: a study of the receptor gene knockout mice. Eur J Pharmacol 391:81–89, PMID: 10720638

    Article  CAS  PubMed  Google Scholar 

  • Mojtahedin A, Tamaddonfard E, Zanbouri A (2008) Antinociception induced by central administration of histamine in the formalin test in rats. Indian J Physiol Pharmacol 52:249–254, PMID: 19552055

    CAS  PubMed  Google Scholar 

  • Munn EM, Harte SE, Lagman A, Borszcz GS (2009) Contribution of the periaqueductal gray to the suppression of pain affect produced by administration of morphine into the intralaminar thalamus of rat. J Pain 10:426–435, PMID: 19231299

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Netti C, Bossa R, Galatulas I, Sibilia V, Pecile A (1984) Antinociceptive effect of centrally administered cimetidine and dimaprit in the rat. Pharmacology 28:262–267, PMID: 6233621

    Article  CAS  PubMed  Google Scholar 

  • Netti C, Guidobono F, Sibilia V, Villa I, Cazzamalli E, Pecile A (1988) Central effects of the histamine H2 receptor agonist and antagonist on nociception in rats. Agents Actions 23:247–249, PMID: 2899383

    Article  CAS  PubMed  Google Scholar 

  • Netti C, Sibilia V, Guidobono F, Villani P, Pecile A, Braga PC (1994) Evidence for an inhibitory role of central histamine on carrageenan-induced hyperalgesis. Neuropharmacology 33:205–210, PMID: 8035905

    Article  CAS  PubMed  Google Scholar 

  • Parada CA, Tambeli CH, Cunha FQ, Ferreira SH (2001) The major role of histamine and 5-hydroxytryptamine in formalin-iduced nociception. Neuroscience 102:937–944, PMID: 11182255

    Article  CAS  PubMed  Google Scholar 

  • Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates, 6th edn. Elsevier Academic Press, San Diego

    Google Scholar 

  • Raboisson P, Dallel R (2004) The orofacial formalin test. Neurosci Biobehav Rev 28:219–226, PMID: 15172765

    Article  PubMed  Google Scholar 

  • Reisi Z, Haghparast A, Pahlevani P, Shamsizadeh A, Haghparast A (2014) Interaction between the dopaminergic and opioidergic systems in dorsal hippocampus in modulation of formalin-induced orofacial pain in rats. Pharmacol Biochem Behav 124:220–225, PMID: 24955867

    Article  CAS  PubMed  Google Scholar 

  • Rosenfeld JP, Stocco S (1981) Effects of midbrain, bulbar and combined morphine microinjections and systemic injections on orofacial nociception and rostral trigeminal stimulation: independent midbrain and bulbar opiate analgesia systems? Brain Res 215:342–348, PMID: 7260593

    Article  CAS  PubMed  Google Scholar 

  • Sakurada S, Orito T, Furuta S, Watanabe H, Mobarakeh JI, Yanai K, Watanabe T, Sato T, Onodera K, Sakurada C, Sakurada T (2003) Intrathecal histamine induces spinally mediated behavioral responses through tachykinin NK1 receptors. Pharmacol Biochem Behav 74:487–493, PMID: 12479971

    Article  CAS  PubMed  Google Scholar 

  • Stein C, Zollner C (2009) Opioids and sensory nerves. Handb Exp Pharmacol 194:495–518, PMID: 19655116

    Article  CAS  PubMed  Google Scholar 

  • Tamaddonfard E, Hamzeh-Gooshchi N (2014) Effects of administration of histamine and its H1, H2, and H3 receptor antagonists into the primary somatosensory cortex on inflammatory pain in rats. Iran J Basic Med Sci 17:55–61, PMID: 24592308

    PubMed Central  CAS  PubMed  Google Scholar 

  • Tamaddonfard E, Rahimi S (2004) Central effect of histamine and peripheral effect of histidine on the formalin-induced pain response in mice. Clin Exp Pharmacol Physiol 31:518–522, PMID: 15298544

    Article  CAS  PubMed  Google Scholar 

  • Tamaddonfard E, Erfanparast A, Farshid AA, Khalilzadeh E (2011) Interaction between histamine and morphine at the level of the hippocampus in the formalin-induced orofacial pain in rats. Pharmacol Rep 63:423–432, PMID: 21602597

    Article  CAS  PubMed  Google Scholar 

  • Tang JS, Qu CL, Huo FQ (2009) The thalamic nucleus submedius and ventrolateral orbital cortex are involved in nociceptive modulation: a novel pain modulation pathway. Prog Neurobiol 89:383–389, PMID: 19819292

    Article  PubMed  Google Scholar 

  • Thoburn KK, Hough LB, Nalwalk JW, Mischler SA (1994) Histamine-induced modulation of nociceptive responses. Pain 58:29–37, PMID: 7970837

    Article  CAS  PubMed  Google Scholar 

  • Vizuete ML, Traiffort E, Bouthenet ML, Ruat M, Souil E, Tardivel-Lacombe J, Schwartz JC (1997) Detailed mapping of the histamine H2 receptor and its gene transcripts in guinea-pig brain. Neuroscience 80:321–343, PMID: 9284338

    Article  CAS  PubMed  Google Scholar 

  • Wei H, Jin CY, Viisanen H, You HJ, Pertovaara A (2014) Histamine in the locus coeruleus promotes descending noradrenergic inhibition of neuropathic hypersensitivity. Pharmacol Res 90:58–66, PMID: 25304183

    Article  CAS  PubMed  Google Scholar 

  • Wong JC (1999) Further study on the effects of histamine H2 receptor agonist and antagonists on restraint-induced antinociception in mice. Methods Find Exp Clin Pharmacol 21:403–407, PMID: 10445232

    Article  CAS  PubMed  Google Scholar 

  • Yang ZJ, Tang JS, Jia H (2002) Morphine microinjections into the rat nucleus submedius depress nociceptive behavior in the formalin test. Neurosci Lett 328:141–144, PMID: 12133575

    Article  CAS  PubMed  Google Scholar 

  • Yen CT, Lu PL (2013) Thalamus and pain. Acta Anaesthesiol Taiwan 51:73–80, PMID: 23968658

    Article  PubMed  Google Scholar 

  • Yousofizadeh S, Tamaddonfard E, Farshid AA (2015) The role of nicotinic acetylcholine and opioid systems of the ventral orbital cortex in modulation of formalin-induced orofacial pain in rats. Eur J Pharmacol 758:147–152, PMID: 25864612

    Article  CAS  PubMed  Google Scholar 

  • Zhang YQ, Tang JS, Yuan B, Jia H (1995) Effects of thalamic nucleus submedius lesions on the rat tail flick reflex inhibition evoked by hindlimb electrical stimulation in the rat. NeuroReport 6:1237–1240, PMID: 7669977

    Article  CAS  PubMed  Google Scholar 

  • Zhao M, Li Q, Tang JS (2006) The effects of microinjection of morphine into thalamic nucleus submedius on formalin-evoked nociceptive responses of neurons in the rat spinal dorsal horn. Neurosci Lett 401:103–107, PMID: 16556485

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Physiology, Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, 57153-1177, Iran

    Amir Erfanparast, Esmaeal Tamaddonfard, Mina Taati & Milad Dabaghi

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  1. Amir Erfanparast
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  2. Esmaeal Tamaddonfard
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  3. Mina Taati
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  4. Milad Dabaghi
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Correspondence to Amir Erfanparast.

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Erfanparast, A., Tamaddonfard, E., Taati, M. et al. Role of the thalamic submedius nucleus histamine H1 and H2 and opioid receptors in modulation of formalin-induced orofacial pain in rats. Naunyn-Schmiedeberg's Arch Pharmacol 388, 1089–1096 (2015). https://doi.org/10.1007/s00210-015-1143-0

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