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Journal of Neural Transmission

, Volume 120, Issue 11, pp 1533–1538 | Cite as

Involvement of cannabinoid CB1 receptors in the antinociceptive effect of dipyrone

  • Pinar Elmas
  • Ahmet UlugolEmail author
Translational Neurosciences - Original Article

Abstract

Cannabinoid CB1 receptors have been implicated in the antinociceptive effect of paracetamol. In the current study, we examined whether blockade of CB1 receptors prevent the analgesic activity of dipyrone, in a similar way to paracetamol. Hot-plate and tail-flick tests were used to assess the antinociceptive activity in mice. Dipyrone and WIN 55,212-2, a cannabinoid agonist, exerted significant antinociceptive effects in both hot-plate and tail flick tests. The CB1 receptor antagonist, AM-251 (3 mg/kg), at a dose which had no effect when used alone, did not alter the antinociceptive effect of dipyrone, whereas completely prevented the antinociceptive activity of WIN 55,212-2 in both thermal antinociceptive tests. Our findings suggest that, unlike paracetamol, cannabinoid CB1 receptors do not participate in the antinociceptive action of dipyrone when acute pain tests used.

Keywords

Dipyrone WIN 55,212-2 CB1 receptor Antinociception 

Notes

Acknowledgments

This work was supported by a grant from Trakya University Research Council (TUBAP-2012/58). The authors have no conflicts of interests to report.

References

  1. Akman H, Aksu F, Gultekin I, Ozbek H, Oral U, Doran F, Baysal F (1996) A possible central antinociceptive effect of dipyrone in mice. Pharmacology 53:71–78PubMedCrossRefGoogle Scholar
  2. Beirith A, Santos ARS, Rodrigues ALS, Creczynski-Pasa TB, Calixto JB (1998) Spinal and supraspinal antinociceptive action of dipyrone in formalin, capsaicin and glutamate tests. Study of the mechanism of action. Eur J Pharmacol 345:233–245PubMedCrossRefGoogle Scholar
  3. Bujalska M (2004) Effect of nonselective and selective opioid receptors antagonists on antinociceptive action of APAP [Part III]. pol J Pharmacol 56:539–545PubMedGoogle Scholar
  4. Campos C, De Gregorio R, Garcia-Nieto R, Gago F, Ortiz P, Alemany S (1999) Regulation of cyclooxygenase activity by metamizol. Eur J Pharmacol 378:339–347PubMedCrossRefGoogle Scholar
  5. Dani M, Guindon J, Lambert C, Beaulieu P (2007) The local antinociceptive effects of paracetamol in neuropathic pain are mediated by cannabinoid receptors. Eur J Pharmacol 573:214–215PubMedCrossRefGoogle Scholar
  6. Dogrul A, Seyrek M, Yalcin B, Ulugol A (2012) Involvement of descending serotonergic and noradrenergic pathways in cannabinoid CB1 receptor-mediated antinociception. Prog Neurpsychopharmacol Biol Psychiatry 38:97–105. doi: 10.1016/j.pnpbp.2012.01.007 CrossRefGoogle Scholar
  7. Escobar W, Ramirez K, Avila C, Limongi R, Vanegas H, Vazquez E (2012) Metamizol, a non-opioid analgesic, acts via endocannabinoids in the PAG-RVM axis during inflammation in rats. Eur J Pain 16:676–689. doi: 10.1002/j.1532-2149.2011.00057.x PubMedCrossRefGoogle Scholar
  8. Gunduz O, Karadag HC, Ulugol A (2011a) Synergistic anti-allodynic effects of nociceptin/orphanin FQ and cannabinoid systems in neuropathic mice. Pharmacol Biochem Behav 99:540–544. doi: 10.1016/j.pbb.2011.05.029 PubMedCrossRefGoogle Scholar
  9. Gunduz O, Oltulu C, Guven R, Buldum D, Ulugol A (2011b) Pharmacological and behavioral characterization of the saphenous chronic constriction injury model of neuropathic pain in rats. Neurol Sci 32:1135–1142. doi: 10.1007/s10072-011-0761-7 PubMedCrossRefGoogle Scholar
  10. Gunduz O, Oltulu C, Ulugol A (2011c) Role of GLT-1 transporter activation in prevention of cannabinoid tolerance by the beta-lactam antibiotic, ceftriaxone, in mice. Pharmacol Biochem Behav 99:100–103. doi: 10.1016/j.pbb.2011.04.012 PubMedCrossRefGoogle Scholar
  11. Hernandez N, Vanegas H (2001) Antinociception induced by PAG-microinjected dipyrone (metamizol) in rats: involvement of spinal endogenous opioids. Brain Res 896:175–178PubMedCrossRefGoogle Scholar
  12. Hernandez-Delgadillo GP, Cruz SL (2006) Endogenous opioids are involved in morphine and dipyrone analgesic potentiation in the tail flick test in rats. Eur J Pharmacol 546:54–59PubMedCrossRefGoogle Scholar
  13. Isguzar O, Baris S, Bozkurt A, Can B, Bilge S, Ture H (2012) Evaluation of antinociceptive and neurotoxic effects of intrathecal dexmedetomidine in rats. Balkan Med J 29:354–357. doi: 10.5152/balkanmedj.2012.034 Google Scholar
  14. Lorenzetti BB, Ferreira SH (1996) Activation of the arginine-nitric oxide pathway in primary sensory neurons contributes to dipyrone-induced spinal and peripheral analgesia. Inflamm Res 45:308–311PubMedCrossRefGoogle Scholar
  15. Mallet C, Daulhac L, Bonnefont J, Ledent C, Etienne M, Chapuy E, Libert F, Eschalier A (2008) Endocannabinoid and serotonergic systems are needed for acetaminophen-induced analgesia. Pain 139:190–200. doi: 10.1016/j.pain.2008.03.030 PubMedCrossRefGoogle Scholar
  16. Neugebauer V, Schaible HG, He X, Lücke T, Gündling P, Schmidt RF (1994) Electrophysiological evidence for a spinal antinociceptive action of dipyrone. Agents Actions 41:62–70PubMedCrossRefGoogle Scholar
  17. Ottani A, Leone S, Sandrini M, Ferrari A, Bertolini A (2006) The analgesic activity of paracetamol is prevented by the blockade of cannabinoid CB1 receptors. Eur J Pharmacol 531:280–281PubMedCrossRefGoogle Scholar
  18. Rogosch T, Sinning C, Podlewski A, Watzer B, Schlosburg J, Lichtman AH, Cascio MG, Bisogno T, Di Marzo V, Nüsing R, Imming P (2012) Novel bioactive metabolites of dipyrone (metamizol). Bioorgan Med Chem 20:101–107. doi: 10.1016/j.bmc.2011.11.028 CrossRefGoogle Scholar
  19. Sandrini M, Vitale G, Ottani S, Pini L (2001) The effect of paracetamol and morphine combination on dynorphin A levels in the rat brain. Biochem Pharmacol 61:1409–1416PubMedCrossRefGoogle Scholar
  20. Schlosburg JE, Kinsey SG, Lichtman AH (2009) Targeting fatty acid amide hydrolase (FAAH) to treat pain and inflmmation. AAPS J 11:39–44. doi: 10.1208/s12248-008-9075-y PubMedCrossRefGoogle Scholar
  21. Schlosburg JE, Radanova L, Di Marzo V, Imming P, Lichtman AH (2012) Evaluation of the endogenous cannabinoid system in mediating the behavioral effects of dipyrone (metamizol) in mice. Behav Pharmacol 23:722–726. doi: 10.1097/FBP.0b013e3283584794 PubMedCrossRefGoogle Scholar
  22. Seyrek M, Kahraman S, Deveci MS, Yesilyurt O, Dogrul A (2010) Systemic cannabinoids produce CB1-mediated antinociception by activation of descending serotonergic pathways that act upon spinal 5-HT7 and 5-HT2A receptors. Eur J Pharmacol 649:183–194. doi: 10.1016/j.ejphar.2010.09.039 PubMedCrossRefGoogle Scholar
  23. Siebel JS, Beirith A, Calixto JB (2004) 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 1003:61–67PubMedCrossRefGoogle Scholar
  24. Taylor J, Mellström B, Fernaud I, Naranjo JR (1998) Metamizol potentiates morphine effects on visceral pain and evoked c-Fos immunoreactivity in spinal cord. Eur J Pharmacol 351:39–47PubMedCrossRefGoogle Scholar
  25. Ulugol A, Karadag HC, Ipci Y, Tamer M, Dokmeci I (2004) The effect of WIN 55,212-2, a cannabinoid agonist, on tactile allodynia in diabetic rats. Neurosci Lett 371:167–170PubMedCrossRefGoogle Scholar
  26. Ulugol A, Ozyigit F, Yesilyurt O, Dogrul A (2006) The additive antinociceptive interaction between WIN 55,212-2, a cannabinoid agonist, and ketorolac. Anesth Analg 102:443–447PubMedCrossRefGoogle Scholar
  27. Vanegas H, Schaible HG (2001) Prostaglandins and cyclooxygenases in the spinal cord. Prog Neurobiol 64:327–363PubMedCrossRefGoogle Scholar
  28. Vanegas H, Tortorici V (2002) Opioidergic effects of nonopioid analgesics on the central nervous system. Cell Mol Neurobiol 5–6:655–661CrossRefGoogle Scholar
  29. Vasquez E, Vanegas H (2000) The antinociceptive effect of PAG-microinjected dipyrone in rats is mediated by endogenous opioids of the rostral ventromedial medulla. Brain Res 854:249–252PubMedCrossRefGoogle Scholar
  30. Vazquez E, Hernandez N, Escobar W, Vanegas H (2005) 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 1048:211–217PubMedCrossRefGoogle Scholar
  31. Vazquez E, Escobar W, Ramirez K, Vanegas H (2007) A nonopioid analgesic acts upon the PAG-RVM axis to reverse inflammatory hyperalgesia. Eur J Neurosci 25:471–479PubMedCrossRefGoogle Scholar
  32. Yilmaz I, Ulugol A (2009) The effect of nitric oxide synthase inhibitors on the development of analgesic tolerance to dipyrone in mice. Int J Neurosci 119:755–764. doi: 10.1080/00207450902776192 PubMedCrossRefGoogle Scholar
  33. Zimmermann M (1983) Ethical guidelines for investigations of experimental pain in conscious animals. Pain 16:109–110PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  1. 1.Department of Medical Pharmacology, Faculty of MedicineTrakya UniversityEdirneTurkey

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