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Descending serotonergic and noradrenergic systems do not regulate the antipruritic effects of cannabinoids*

Published online by Cambridge University Press:  08 April 2016

Zeynep Gizem Todurga ,
Ozgur Gunduz ,
Cetin Hakan Karadag  and
Ahmet Ulugol
Zeynep Gizem Todurga
Affiliation:
Department of Medical Pharmacology, Faculty of Medicine, Trakya University, 22030-Edirne, Turkey
Ozgur Gunduz
Affiliation:
Department of Medical Pharmacology, Faculty of Medicine, Trakya University, 22030-Edirne, Turkey
Cetin Hakan Karadag
Affiliation:
Department of Medical Pharmacology, Faculty of Medicine, Trakya University, 22030-Edirne, Turkey
Ahmet Ulugol*
Affiliation:
Department of Medical Pharmacology, Faculty of Medicine, Trakya University, 22030-Edirne, Turkey
*
Prof. Ahmet Ulugol, MD, Department of Medical Pharmacology, Faculty of Medicine, Trakya University, Edirne, Turkey. Tel:+90 284 235 3925; Fax: +90 284 235 3925; E-mail: [email protected]; [email protected]
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Abstract

Background

For centuries, cannabinoids have been known to be effective in pain states. Itch and pain are two sensations sharing a lot in common.

Objective

The goal of this research was to observe whether the cannabinoid agonist WIN 55,212-2 reduces serotonin-induced scratching behaviour and whether neurotoxic destruction of descending serotonergic and noradrenergic pathways mediate the antipruritic effect of WIN 55,212-2.

Material and methods

Scratching behaviour was induced by intradermal injection of serotonin (50 µg/50 µl/mouse) to Balb/c mice. The neurotoxins 5,7-dihydroxytryptamine (5,7-DHT, 50 μg/mouse) and 6-hydroxydopamine (6-OHDA, 20 μg/mouse) are applied intrathecally to deplete serotonin and noradrenaline in the spinal cord. WIN 55,212-2 (1, 3, 10 mg/kg, i.p.) dose-dependently attenuated serotonin-induced scratches. Neurotoxic destruction of neither the serotonergic nor the noradrenergic systems by 5,7-DHT and 6-OHDA, respectively, had any effect on the antipruritic action of WIN 55,212-2.

Conclusion

Our findings indicate that cannabinoids dose-dependently reduce serotonin-induced scratching behaviour and neurotoxic destruction of descending inhibitory pathways does not mediate this antipruritic effect.

Keywords

cannabinoid systemdescending inhibitionWIN 55,212-2pruritus
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 28 , Issue 6 , December 2016 , pp. 321 - 326
Copyright
© Scandinavian College of Neuropsychopharmacology 2016 

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Footnotes

*

Submitted to ‘8th World Congress of the World Institute of Pain (WIP)’, New York, USA, 20–23 May 2016.

References

1. Ikoma, A, Steinhoff, M, Stander, S, Yosipovitch, G, Schmelz, M. The neurobiology of itch. Nat Rev Neurosci 2006;7:535–547.Google Scholar
2. Schmelz, M. Itch and pain. Neurosci Biobehav R 2010;34:171–176.CrossRefGoogle ScholarPubMed
3. Gotoh, Y, Omori, Y, Andoh, T, Kuraishi, Y. Tonic inhibition of allergic itch signaling by the descending noradrenergic system in mice. J Pharmacol Sci 2011;115:417–420.Google Scholar
4. Cevikbas, F, Steinhoff, M, Ikoma, A. Role of spinal neurotransmitter receptors in itch: new insights into therapies and drug development. CNS Neurosci Ther 2011;17:742–749.CrossRefGoogle ScholarPubMed
5. Davidson, S, Giesler, GJ. The multiple pathways for itch and their interactions with pain. Trends Neurosci 2010;33:550–558.Google Scholar
6. Horvath, G, Joo, G, Kekesi, G et al. Inhibition of itch-related responses at spinal level in rats. Acta Physiol Hung 2011;98:480–490.Google Scholar
7. Ross, SE. Pain and itch: insights into the neural circuits of aversive somatosensation in health and disease. Curr Opin Neurobiol 2011;21:880–887.Google Scholar
8. Kuraishi, Y. Potential new therapeutic targets for pathological pruritus. Biol Pharm Bull 2013;36:1228–1234.Google Scholar
9. Gunduz, O, Oltulu, C, Ulugol, A. Role of GLT-1 transporter activation in prevention of cannabinoid tolerance by the beta-lactam antibiotic, ceftriaxone, in mice. Pharmacol Biochem Behav 2011;99:100–103.Google Scholar
10. Dogrul, A, Seyrek, M, Yalcin, B, Ulugol, A. Involvement of descending serotonergic and noradrenergic pathways in CB1 receptor-mediated antinociception. Prog Neuro-Psychoph 2012;38:97–105.Google Scholar
11. Ulugol, A. The endocannabinoid system as a potential therapeutic target for pain modulation. Balkan Med J 2014;31:115–120.Google Scholar
12. Grotenhermen, F, Muller-Vahl, K. The therapeutic potential of cannabis and cannabinoids. Dtsch Arztebl Int 2012;109:495–501.Google Scholar
13. Kalliomaki, J, Annas, P, Huizar, K et al. Evaluation of the analgesic efficacy and psychoactive effects of AZD1940, a novel peripherally acting cannabinoid agonist, in human capsaicin-induced pain and hyperalgesia. Clin Exp Pharmacol P 2013;40:212–218.CrossRefGoogle ScholarPubMed
14. Pryce, G, Visintin, C, Ramagopalan, SV et al. Control of spasticity in a multiple sclerosis model using central nervous system-excluded CB1 cannabinoid receptor agonists. FASEB J 2014;28:117–130.Google Scholar
15. Toth, C, Mawani, S, Brady, S et al. An enriched-enrolment, randomized withdrawal, flexible-dose, double-blind, placebo-controlled, parallel assignment efficacy study of nabilone as adjuvant in the treatment of diabetic peripheral neuropathic pain. Pain 2012;153:2073–2082.CrossRefGoogle ScholarPubMed
16. Darmani, NA, Pandya, DK. Involvement of other neurotransmitters in behaviors induced by the cannabinoid CB1 receptor antagonist SR 141716A in naive mice. J Neural Transm 2000;107:931–945.CrossRefGoogle ScholarPubMed
17. Schlosburg, JE, O’Neal, ST, Conrad, DH, Lichtman, AH. CB1 receptors mediate rimonabant-induced pruritic responses in mice: investigation of locus of action. Psychopharmacology 2011;216:323–331.Google Scholar
18. Tosun, NC, Gunduz, O, Ulugol, A. Attenuation of serotonin-induced itch responses by inhibition of endocannabinoid degradative enzymes, fatty acid amide hydrolase and monoacylglycerol lipase. J Neural Transm 2014;122:363–367.CrossRefGoogle ScholarPubMed
19. Millan, MJ. Descending control of pain. Prog Neurobiol 2002;66:355–474.Google Scholar
20. Yanarates, O, Dogrul, A, Yildirim, V et al. Spinal 5-HT7 receptors play an important role in the antinociceptive and antihyperalgesic effects of tramadol and its metabolite, O-desmethyltramadol, via activation of descending serotonergic pathways. Anesthesiology 2010;112:696–710.CrossRefGoogle ScholarPubMed
21. Gutierrez, T, Nackley, AG, Neely, MH, Freeman, KG, Edwards, GL, Hohmann, AG. Effects of neurotoxic destruction of descending noradrenergic pathways on cannabinoid antinociception in models of acute and tonic nociception. Brain Res 2003;987:176–185.CrossRefGoogle ScholarPubMed
22. Seyrek, M, Kahraman, S, Deveci, MS, Yesilyurt, O, Dogrul, A. 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 2010;649:183–194.Google Scholar
23. Ulugol, A, Karadag, HC, Ipci, Y, Tamer, M, Dokmeci, I. The effect of WIN 55,212-2, a cannabinoid agonist, on tactile allodynia in diabetic rats. Neurosci Lett 2004;371:167–170.Google Scholar
24. Saglam, G, Gunduz, O, Ulugol, A. Blockade of cannabinoid CB1 and CB2 receptors does not prevent the antipruritic effect of systemic paracetamol. Acta neurologica Belgica 2014;114:307–309.CrossRefGoogle Scholar
25. Hung, KC, Wu, HE, Mizoguchi, H, Leitermann, R, Tseng, LF. Intrathecal treatment with 6-hydroxydopamine or 5,7-dihydroxytryptamine blocks the antinociception induced by endomorphin-1 and endomorphin-2 given intracerebroventricularly in the mouse. J Pharmacol Sci 2003;93:299–306.Google Scholar
26. 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.Google Scholar
27. Darmani, NA. Cannabinoid agonists differentially inhibit two DOI-induced 5-HT2A-mediated behaviors in mice. Eur J Neurosci 2000;12:95.Google Scholar
28. Janoyan, JJ, Crim, JL, Darmani, NA. Reversal of SR 141716A-induced head-twitch and ear-scratch responses in mice by Delta(9)-THC and other cannabinoids. Pharmacol Biochem Behav 2002;71:155–162.Google Scholar
29. Dvorak, M, Watkinson, A, McGlone, F, Rukwied, R. Histamine induced responses are attenuated by a cannabinoid receptor agonist in human skin. Inflamm Res 2003;52:238–245.Google Scholar
30. Schlosburg, JE, Boger, DL, Cravatt, BF, Lichtman, AH. Endocannabinoid modulation of scratching response in an acute allergenic model: a new prospective neural therapeutic target for pruritus. J Pharmacol Exp Ther 2009;329:314–323.Google Scholar
31. Gomes, FV, Del Bel, EA, Guimaraes, FS. Cannabidiol attenuates catalepsy induced by distinct pharmacological mechanisms via 5-HT1A receptor activation in mice. Prog Neuro-Psychoph 2013;46:43–47.CrossRefGoogle ScholarPubMed
32. Gomes, FV, Casarotto, PC, Resstel, LBM, Guimaraes, FS. Facilitation of CB1 receptor-mediated neurotransmission decreases marble burying behavior in mice. Prog Neuro-Psychoph 2011;35:434–438.Google Scholar
33. Gunduz, O, Topuz, RD, Karadag, CH, Ulugol, A. Analysis of the anti-allodynic effects of combination of a synthetic cannabinoid and a selective noradrenaline re-uptake inhibitor in nerve injury-induced neuropathic mice. Eur J Pain 2015;33:465–471.Google Scholar
34. Kinsey, SG, Nomura, DK, O’Neal, ST et al. Inhibition of monoacylglycerol lipase attenuates nonsteroidal anti-inflammatory drug-induced gastric hemorrhages in mice. J Pharmacol Exp Ther 2011;338:795–802.Google Scholar
35. Spradley, JM, Davoodi, A, Gee, LB, Carstens, MI, Carstens, E. Differences in peripheral endocannabinoid modulation of scratching behavior in facial vs. spinally-innervated skin. Neuropharmacology 2012;63:743–749.Google Scholar
36. Kusakabe, K, Iso, Y, Tada, Y et al. Selective CB2 agonists with anti-pruritic activity: discovery of potent and orally available bicyclic 2-pyridones. Bioorgan Med Chem 2013;21:3154–3163.Google Scholar
37. Odan, M, Ishizuka, N, Hiramatsu, Y et al. Discovery of S-777469: an orally available CB2 agonist as an antipruritic agent. Bioorg Med Chem Lett 2012;22:2803–2806.Google Scholar
38. Andoh, T, Gotoh, Y, Kuraishi, Y. Milnacipran inhibits itch-related responses in mice through the enhancement of noradrenergic transmission in the spinal cord. J Pharmacol Sci 2013;123:199–202.Google Scholar
39. Gotoh, Y, Andoh, T, Kuraishi, Y. Clonidine inhibits itch-related response through stimulation of alpha(2)-adrenoceptors in the spinal cord in mice. Eur J Pharmacol 2011;650:215–219.Google Scholar
40. Gotoh, Y, Andoh, T, Kuraishi, Y. Noradrenergic regulation of itch transmission in the spinal cord mediated by alpha-adrenoceptors. Neuropharmacology 2011;61:825–831.Google Scholar