Hostname: page-component-cd9895bd7-fscjk Total loading time: 0 Render date: 2024-12-23T00:01:31.441Z Has data issue: false hasContentIssue false
  • English
  • Français

Contribution of nociceptin/orphanin FQ receptors to the anti-nociceptive and hypothermic effects of dipyrone

Published online by Cambridge University Press:  03 December 2014

Ismet Hande Ertin ,
Ozgur Gunduz  and
Ahmet Ulugol
Ismet Hande Ertin
Affiliation:
Department of Medical Pharmacology, Faculty of Medicine, Trakya University, Edirne, Turkey
Ozgur Gunduz
Affiliation:
Department of Medical Pharmacology, Faculty of Medicine, Trakya University, Edirne, Turkey
Ahmet Ulugol*
Affiliation:
Department of Medical Pharmacology, Faculty of Medicine, Trakya University, Edirne, Turkey
*
Prof. Ahmet Ulugol, Department of Medical Pharmacology, Faculty of Medicine, Trakya University, 22030-Edirne, Turkey. Tel/Fax: +90 284 235 3925 E-mail: [email protected]; [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Dipyrone is one of the most commonly used non-opioid analgesic and antipyretic drug. Its anti-nociceptive and hypothermic effects have long been suspected to be centrally mediated. The involvement of the most recently discovered opioid peptide, nociceptin/orphanin FQ (N/OFQ), and its receptor (NOP) in pain transmission is controversial. It appears to be pro-nociceptive when administered supra-spinally, but exerts anti-nociceptive effects when injected spinally or systemically.

Objective

Investigation of the role of the N/OFQ system in paracetamol-induced anti-nociception and hypothermia led us to determine its role in the anti-nociceptive and hypothermic effects of dipyrone.

Material and Methods

Hot-plate and tail-flick tests were used to assess nociception, and a rectal thermometer was used to measure rectal temperature in mice.

Results

Mice injected with dipyrone (150, 300, 600 mg/kg, i.p.) displayed dose-related anti-nociception and hypothermia. The NOP receptor antagonist JTC-801 (3 mg/kg, i.p.), at a dose that exerted no effect when used alone, alleviated dipyrone-induced anti-nociception but did not reverse dipyrone-induced hypothermia.

Conclusion

We conclude that NOP receptors participate in the anti-nociceptive, but not in the hypothermic, effects of dipyrone.

Keywords

anti-nociceptiondipyronehypothermiaJTC-801N/OFQ
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 27 , Issue 1 , February 2015 , pp. 48 - 52
Check for updates
Copyright
© Scandinavian College of Neuropsychopharmacology 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Akman, H, Aksu, F, Gultekin, Iet al.. A possible central antinociceptive effect of dipyrone in mice. Pharmacology 1996;53:71–78.Google Scholar
2.Carlsson, KH, Jurna, I. The role of descending inhibition in the antinociceptive effects of the pyrazolone derivatives, metamizol (Dipyrone) and aminophenazone (Pyramidon). N-S Arch Pharmacol 1987;335:154–159.Google Scholar
3.Vazquez, E, Hernandez, N, Escobar, W, Vanegas, H. Antinociception induced by intravenous dipyrone (metamizol) upon dorsal horn neurons: involvement of endogenous opioids at the periaqueductal gray matter, the nucleus raphe magnus, and the spinal cord in rats. Brain Res 2005;1048:211–217.CrossRefGoogle ScholarPubMed
4.Vanegas, H, Tortorici, V. Opioidergic effects of nonopioid analgesics on the central nervous system. Cell Mol Neurobiol 2002;22:655–661.Google Scholar
5.Hernandez-Delgadillo, GP, Cruz, SL. Endogenous opioids are involved in morphine and dipyrone analgesic potentiation in the tail flick test in rats. Eur J Pharmacol 2006;546:54–59.Google Scholar
6.Ulugol, A. The endocannabinoid system as a potential therapeutic target for pain modulation. Balkan Med J 2014;31:115–120.CrossRefGoogle ScholarPubMed
7.Escobar, W, Ramirez, K, Avila, C, Limongi, R, Vanegas, H, Metamizol, Vazquez E. A non-opioid analgesic, acts via endocannabinoids in the PAG-RVM axis during inflammation in rats. Eur J Pain 2012;16:676–689.CrossRefGoogle ScholarPubMed
8.Rogosch, T, Sinning, C, Podlewski, Aet al.Novel bioactive metabolites of dipyrone (metamizol). Bioorgan Med Chem 2012;20:101–107.Google Scholar
9.Heinricher, MM. Nociceptin/orphanin FQ: pain, stress and neural circuits. Life Sci 2005;77:3127–3132.Google Scholar
10.Mika, J, Obara, I, Przewlocka, B. The role of nociceptin and dynorphin in chronic pain: implications of neuro-glial interaction. Neuropeptides 2011;45:247–261.CrossRefGoogle ScholarPubMed
11.Rawls, SM, Schroeder, JA, Ding, Z, Rodriguez, T, Zaveri, N. NOP receptor antagonist, JTC-801, blocks cannabinoid-evoked hypothermia in rats. Neuropeptides 2007;41:239–247.Google Scholar
12.Uezu, K, Sei, H, Sano, Aet al.Lack of nociceptin receptor alters body temperature during resting period in mice. Neuroreport 2004;15:751–755.Google Scholar
13.Mallet, C, Daulhac, L, Bonnefont, Jet al.Endocannabinoid and serotonergic systems are needed for acetaminophen-induced analgesia. Pain 2008;139:190–200.Google Scholar
14.Dogrul, A, Seyrek, M, Akgul, EO, Cayci, T, Kahraman, S, Bolay, H. Systemic paracetamol-induced analgesic and antihyperalgesic effects through activation of descending serotonergic pathways involving spinal 5-HT7 receptors. Eur J Pharmacol 2012;677:93–101.CrossRefGoogle ScholarPubMed
15.Sandrini, M, Vitale, G, Pini, LA, Lopetuso, G, Romualdi, P, Candeletti, S. Nociceptin/orphanin FQ prevents the antinociceptive action of paracetamol on the rat hot plate test. Eur J Pharmacol 2005;507:43–48.Google Scholar
16.Corley, G, Rawls, SM. Opioid, cannabinoid CB1 and NOP receptors do not mediate APAP-induced hypothermia in rats. Pharmacol Biochem Behav 2009;92:503–507.Google Scholar
17.Gunduz, O, Karadag, HC, Ulugol, A. Synergistic anti-allodynic effects of nociceptin/orphanin FQ and cannabinoid systems in neuropathic mice. Pharmacol Biochem Behav 2011;99:540–544.Google Scholar
18.Elmas, P, Ulugol, A. Involvement of cannabinoid CB1 receptors in the antinociceptive effect of dipyrone. J Neural Transm 2013;120:1533–1538.Google Scholar
19.Yilmaz, I, Ulugol, A. The effect of nitric oxide synthase inhibitors on the development of analgesic tolerance to dipyrone in mice. Int J Neurosci 2009;119:755–764.Google Scholar
20.Escobar, W, Ramirez, K, Avila, C, Limongi, R, Vanegas, H, Metamizol, Vazquez E. A non-opioid analgesic, acts via endocannabinoids in the PAG-RVM axis during inflammation in rats. Eur J Pain 2012;16:676–689.Google Scholar
21.Campos, C, de Gregorio, R, Garcia-Nieto, R, Gago, F, Ortiz, P, Alemany, S. Regulation of cyclooxygenase activity by metamizol. Eur J Pharmacol 1999;378:339–347.Google Scholar
22.Lorenzetti, BB, Ferreira, SH. Activation of the arginine-nitric oxide pathway in primary sensory neurons contributes to dipyrone-induced spinal and peripheral analgesia. Inflamm Res 1996;45:308–311.Google Scholar
23.Siebel, JS, Beirith, A, Calixto, JB. Evidence for the involvement of metabotropic glutamatergic, neurokinin 1 receptor pathways and protein kinase C in the antinociceptive effect of dipyrone in mice. Brain Res 2004;1003:61–67.Google Scholar
24.Tamai, H, Sawamura, S, Takeda, K, Orii, R, Hanaoka, K. Anti-allodynic and anti-hyperalgesic effects of nociceptin receptor antagonist, JTC-801, in rats after spinal nerve injury and inflammation. Eur J Pharmacol 2005;510:223–228.CrossRefGoogle ScholarPubMed
25.Khroyan, TV, Polgar, WE, Orduna, Jet al. Differential effects of nociceptin/orphanin FQ (NOP) receptor agonists in acute versus chronic pain: studies with bifunctional NOP/mu receptor agonists in the sciatic nerve ligation chronic pain model in mice. J Pharmacol Experimental Ther 2011;339:687–693.Google Scholar
26.Mogil, JS, Grisel, JE, Reinscheid, RK, Civelli, O, Belknap, JK, Grandy, DK. Orphanin FQ is a functional anti-opioid peptide. Neuroscience 1996;75:333–337.Google Scholar
27.Gear, RW, Bogen, O, Ferrari, LF, Green, PG, Levine, JD. NOP receptor mediates anti-analgesia induced by agonist–antagonist opioids. Neuroscience 2014;257:139–148.Google Scholar
28.Ayoub, SS, Pryce, G, Seed, MP, Bolton, C, Flower, RJ, Baker, D. Paracetamol-induced hypothermia is independent of cannabinoids and transient receptor potential vanilloid-1 and is not mediated by AM404. Drug Metab Dispos 2011;39:1689–1695.Google Scholar
29.Ayoub, SS, Botting, RM, Goorha, S, Colville-Nash, PR, Willoughby, DA, Ballou, LR. Acetaminophen-induced hypothermia in mice is mediated by a prostaglandin endoperoxide synthase 1 gene-derived protein. Proc Nat Acad Sci U S A 2004;101:11165–11169.Google Scholar
30.Maharaj, DS, Saravanan, KS, Maharaj, H, Mohanakumar, KP, Daya, S. Acetaminophen and aspirin inhibit superoxide anion generation and lipid peroxidation, and protect against 1-methyl-4-phenyl pyridinium-induced dopaminergic neurotoxicity in rats. Neurochem Int 2004;44:355–360.Google Scholar
31.Huang, WT, Wang, JJ, Lin, MT. Antipyretic effect of acetaminophen by inhibition of glutamate release after staphylococcal enterotoxin A fever in rabbits. Neurosci Lett 2004;355:33–36.Google Scholar
32.Schlosburg, JE, Radanova, L, Di Marzo, V, Imming, P, Lichtman, AH. Evaluation of the endogenous cannabinoid system in mediating the behavioral effects of dipyrone (metamizol) in mice. Behav Pharmacol 2012;23:722–726.Google Scholar
33.Malvar, DD, Soares, DM, Fabricio, ASCet al. The antipyretic effect of dipyrone is unrelated to inhibition of PGE(2) synthesis in the hypothalamus. Brit J Pharmacol 2011;162:1401–1409.Google Scholar