Research Article
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Year 2019, Volume: 6 Issue: 1, 0 - 0, 01.02.2019

Abstract

References

  • 1. Davidson S, Giesler GJ. The multiple pathways for itch and their interactions with pain. Trends in Neurosciences 2010;33:550-8.
  • 2. Ikoma A, Cevikbas F, Kempkes C et al. Anatomy and neurophysiology of pruritus. Semin Cutan Med Surg 2011;30:64-70.
  • 3. Koga K, Chen T, Li X-Y et al. Glutamate acts as a neurotransmitter for gastrin-releasing peptide-sensitive and insensitive itch-related synaptic transmission in the mammalian spinal cord. Mol Pain 2011;7:47.
  • 4. Gotoh Y, Omori Y, Andoh T et al. Tonic inhibition of allergic itch signaling by the descending noradrenergic system in mice. J Pharmacol Sci 2011;115:417-20.
  • 5. Ross SE, Mardinly AR, McCord AE et al. Loss of inhibitory interneurons in the dorsal spinal cord and elevated itch in Bhlhb5 mutant mice. Neuron 2010;65:88698.
  • 6. Cevikbas F, Steinhoff M, Ikoma A. Role of spinal neurotransmitter receptors in itch: new insights into therapies and drug development. Cns Neurosci Ther 2011;17:742-9.
  • 7. Kuraishi Y. Potential new therapeutic targets for pathological pruritus. Biol Pharm Bull 2013;36:1228-34.
  • 8. Ross SE. Pain and itch: insights into the neural circuits of aversive somatosensation in health and disease. Current Opinion in Neurobiology 2011;21:880-7.
  • 9. Ulugol A. The endocannabinoid system as a potential therapeutic target for pain modulation. Balkan Med J 2014;31:115-20.
  • 10. Grotenhermen F, Muller-Vahl K. The therapeutic potential of cannabis and cannabinoids. Dtsch Arztebl Int 2012;109:495-501.
  • 11. Schrot RJ, Hubbard JR. Cannabinoids: medical implications. Annals of Medicine 2016;48:128-41.
  • 12. Dvorak M, Watkinson A, McGlone F et al. Histamine-induced responses are attenuated by a cannabinoid receptor agonist in human skin. Inflammation Research 2003;52:238-45.
  • 13. Schlosburg JE, O’Neal ST, Conrad DH et al. CB1 receptors mediate rimonabant-induced pruritic responses in mice: investigation of locus of action. Psychopharmacology 2011;216:323-31.
  • 14. Schlosburg JE, Boger DL, Cravatt BF et al. Endocannabinoid modulation of scratching response in an acute allergenic model: a new prospective neural therapeutic target for pruritus. Journal of Pharmacology and Experimental Therapeutics 2009;329:314-23.
  • 15. Spradley JM, Davoodi A, Gee LB et al. Differences in peripheral endocannabinoid modulation of scratching behavior in facial vs. spinally-innervated skin. Neuropharmacology 2012;63:743-9.
  • 16. 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. Journal of Neural Transmission 2015;122:363-7.
  • 17. Bilir KA, Anli G, Ozkan E et al. Involvement of spinal cannabinoid receptors in the antipruritic effects of WIN 55,212-2, a cannabinoid receptor agonist. Clin Exp Dermatol 2018;43:553-8.
  • 18. Todurga ZG, Gunduz O, Karadag CH et al. Descending serotonergic and noradrenergic systems do not regulate the antipruritic effects of cannabinoids. Acta neuropsychiatrica 2016;28:321-6.
  • 19. Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Delta(9)- tetrahydrocannabinol, cannabidiol and Delta(9)-tetrahydrocannabivarin. Brit J Pharmacol 2008;153:199215.
  • 20. Iffland K, Grotenhermen F. An update on safety and side effects of cannabidiol: a review of clinical data and relevant animal studies. Cannabis Cannabinoid Res 2017;2:139-54.
  • 21. National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals. 2011 (cited 2018 Sep 5). Available from: URL: https://www.ncbi.nlm.nih.gov/books/NBK54050/ doi: 10.17226/12910.
  • 22. Gunduz O, Topuz RD, Todurga ZG et al. Effect of activation of the GLT-1 transporter by a beta-lactam antibiotic on serotonin-induced scratching behavior in mice. Neurophysiology 2015;47:36-9.
  • 23. Ilkaya F, Yesilyurt O, Seyrek M et al. The false-positive responses of analgesic drugs to the intradermal serotonin- and compound 48/80-induced scratches as an animal model of itch. Acta Neurobiol Exp 2016;76:234- 43.
  • 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;114:307-9.
  • 25. Aydemir KD, Gunduz O, Ulugol A. Effects of a nociceptin receptor antagonist on experimentally induced scratching behavior in mice. Neurophysiology 2017;49:130-4.
  • 26. Laprairie RB, Bagher AM, Kelly MEM et al. Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. Brit J Pharmacol 2015;172:4790805.
  • 27. Bisogno T, Hanus L, De Petrocellis L et al. Molecular targets for cannabidiol and its synthetic analogs: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Brit J Pharmacol 2001;134:845-52.
  • 28. Campos AC, Moreira FA, Gomes FV et al. Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders. Philos T R Soc B 2012;367:3364-78.
  • 29. Russo EB, Burnett A, Hall B et al. Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochemical Research 2005;30:1037-43.
  • 30. Viveros MP, Marco EM, File SE. Endocannabinoid system and stress and anxiety responses. Pharmacology Biochemistry and Behavior 2005;81:331-42.
  • 31. Acuna-Goycolea C, Obrietan K, Van Den Pol AN. Cannabinoids excite circadian clock neurons. Journal of Neuroscience 2010;30:10061-6.
  • 32. Hanlon EC, Tasali E, Leproult R et al. Circadian rhythm of circulating levels of the endocannabinoid 2- arachidonoyl glycerol. J Clin Endocr Metab 2015;100:220-6.
  • 33. Schrader NHB, Duipmans JC, Molenbuur B et al. Combined tetrahydrocannabinol and cannabidiol to treat pain in epidermolysis bullosa: a report of three cases. Br J Dermatol 2018 Oct 22. [Epub ahead of print]

SYSTEMIC CANNABIDIOL DOES NOT REDUCE COMPOUND 48/80-INDUCED ITCHING BEHAVIOR IN MICE

Year 2019, Volume: 6 Issue: 1, 0 - 0, 01.02.2019

Abstract

Aims: Cannabinoids are chemical compounds including natural cannabinoids found in the Cannabis plant, their synthetic counterparts, and endocannabinoids. Cannabidiol, a phytocannabinoid derived from the Cannabis plant, exerts anticonvulsant, anxiolytic, anti-inflammatory, neuroprotective, analgesic effects. Although there are many similarities between the pathophysiological mechanisms of pain and itch, researches that investigate the effect of cannabinoids on itching are insufficient. Here, we aimed to examine the antipruritic effect of cannabidiol and the contribution of spinal cannabinoid receptors.

Methods: Male Balb/c mice, weighing 20-30 g, were used. Itching behavior was produced by intradermal injection of compound 48/80 (100 μg/50 μl); cannabidiol (1, 3, 10 mg/kg, ip) was administered 30 minutes before compound 48/80 injections. Then, scratching of the injected site by the hind paws was videotaped for 30 minutes. Locomotor performances were assessed using a rotarod apparatus.

Results: Cannabidiol had no effect on compound 48/80-induced itching behavior at any dose given; moreover, cannabidiol did not produce any impairment on motor function. AM-251, a cannabinoid receptor type 1 antagonist, and AM-630, a cannabinoid receptor type 2 antagonist were administered intrathecally to observe the contribution of spinal cannabinoid receptors to the antipruritic action of cannabidiol. We observed that cannabidol did not possess any effect on itching behaviour.

Conclusion: Our results indicate that systemic administration of cannabidiol does not attenuate compound 48/80 induced itching behavior in mice. 

References

  • 1. Davidson S, Giesler GJ. The multiple pathways for itch and their interactions with pain. Trends in Neurosciences 2010;33:550-8.
  • 2. Ikoma A, Cevikbas F, Kempkes C et al. Anatomy and neurophysiology of pruritus. Semin Cutan Med Surg 2011;30:64-70.
  • 3. Koga K, Chen T, Li X-Y et al. Glutamate acts as a neurotransmitter for gastrin-releasing peptide-sensitive and insensitive itch-related synaptic transmission in the mammalian spinal cord. Mol Pain 2011;7:47.
  • 4. Gotoh Y, Omori Y, Andoh T et al. Tonic inhibition of allergic itch signaling by the descending noradrenergic system in mice. J Pharmacol Sci 2011;115:417-20.
  • 5. Ross SE, Mardinly AR, McCord AE et al. Loss of inhibitory interneurons in the dorsal spinal cord and elevated itch in Bhlhb5 mutant mice. Neuron 2010;65:88698.
  • 6. Cevikbas F, Steinhoff M, Ikoma A. Role of spinal neurotransmitter receptors in itch: new insights into therapies and drug development. Cns Neurosci Ther 2011;17:742-9.
  • 7. Kuraishi Y. Potential new therapeutic targets for pathological pruritus. Biol Pharm Bull 2013;36:1228-34.
  • 8. Ross SE. Pain and itch: insights into the neural circuits of aversive somatosensation in health and disease. Current Opinion in Neurobiology 2011;21:880-7.
  • 9. Ulugol A. The endocannabinoid system as a potential therapeutic target for pain modulation. Balkan Med J 2014;31:115-20.
  • 10. Grotenhermen F, Muller-Vahl K. The therapeutic potential of cannabis and cannabinoids. Dtsch Arztebl Int 2012;109:495-501.
  • 11. Schrot RJ, Hubbard JR. Cannabinoids: medical implications. Annals of Medicine 2016;48:128-41.
  • 12. Dvorak M, Watkinson A, McGlone F et al. Histamine-induced responses are attenuated by a cannabinoid receptor agonist in human skin. Inflammation Research 2003;52:238-45.
  • 13. Schlosburg JE, O’Neal ST, Conrad DH et al. CB1 receptors mediate rimonabant-induced pruritic responses in mice: investigation of locus of action. Psychopharmacology 2011;216:323-31.
  • 14. Schlosburg JE, Boger DL, Cravatt BF et al. Endocannabinoid modulation of scratching response in an acute allergenic model: a new prospective neural therapeutic target for pruritus. Journal of Pharmacology and Experimental Therapeutics 2009;329:314-23.
  • 15. Spradley JM, Davoodi A, Gee LB et al. Differences in peripheral endocannabinoid modulation of scratching behavior in facial vs. spinally-innervated skin. Neuropharmacology 2012;63:743-9.
  • 16. 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. Journal of Neural Transmission 2015;122:363-7.
  • 17. Bilir KA, Anli G, Ozkan E et al. Involvement of spinal cannabinoid receptors in the antipruritic effects of WIN 55,212-2, a cannabinoid receptor agonist. Clin Exp Dermatol 2018;43:553-8.
  • 18. Todurga ZG, Gunduz O, Karadag CH et al. Descending serotonergic and noradrenergic systems do not regulate the antipruritic effects of cannabinoids. Acta neuropsychiatrica 2016;28:321-6.
  • 19. Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Delta(9)- tetrahydrocannabinol, cannabidiol and Delta(9)-tetrahydrocannabivarin. Brit J Pharmacol 2008;153:199215.
  • 20. Iffland K, Grotenhermen F. An update on safety and side effects of cannabidiol: a review of clinical data and relevant animal studies. Cannabis Cannabinoid Res 2017;2:139-54.
  • 21. National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals. 2011 (cited 2018 Sep 5). Available from: URL: https://www.ncbi.nlm.nih.gov/books/NBK54050/ doi: 10.17226/12910.
  • 22. Gunduz O, Topuz RD, Todurga ZG et al. Effect of activation of the GLT-1 transporter by a beta-lactam antibiotic on serotonin-induced scratching behavior in mice. Neurophysiology 2015;47:36-9.
  • 23. Ilkaya F, Yesilyurt O, Seyrek M et al. The false-positive responses of analgesic drugs to the intradermal serotonin- and compound 48/80-induced scratches as an animal model of itch. Acta Neurobiol Exp 2016;76:234- 43.
  • 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;114:307-9.
  • 25. Aydemir KD, Gunduz O, Ulugol A. Effects of a nociceptin receptor antagonist on experimentally induced scratching behavior in mice. Neurophysiology 2017;49:130-4.
  • 26. Laprairie RB, Bagher AM, Kelly MEM et al. Cannabidiol is a negative allosteric modulator of the cannabinoid CB1 receptor. Brit J Pharmacol 2015;172:4790805.
  • 27. Bisogno T, Hanus L, De Petrocellis L et al. Molecular targets for cannabidiol and its synthetic analogs: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Brit J Pharmacol 2001;134:845-52.
  • 28. Campos AC, Moreira FA, Gomes FV et al. Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders. Philos T R Soc B 2012;367:3364-78.
  • 29. Russo EB, Burnett A, Hall B et al. Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochemical Research 2005;30:1037-43.
  • 30. Viveros MP, Marco EM, File SE. Endocannabinoid system and stress and anxiety responses. Pharmacology Biochemistry and Behavior 2005;81:331-42.
  • 31. Acuna-Goycolea C, Obrietan K, Van Den Pol AN. Cannabinoids excite circadian clock neurons. Journal of Neuroscience 2010;30:10061-6.
  • 32. Hanlon EC, Tasali E, Leproult R et al. Circadian rhythm of circulating levels of the endocannabinoid 2- arachidonoyl glycerol. J Clin Endocr Metab 2015;100:220-6.
  • 33. Schrader NHB, Duipmans JC, Molenbuur B et al. Combined tetrahydrocannabinol and cannabidiol to treat pain in epidermolysis bullosa: a report of three cases. Br J Dermatol 2018 Oct 22. [Epub ahead of print]
There are 33 citations in total.

Details

Primary Language English
Journal Section Research Article
Authors

Hatice Demirel This is me 0000-0002-2702-2619

Elif Baksın This is me

Ece Önay Özgür This is me

Ruhan Deniz Topuz This is me

Ahmet Ulugöl

Publication Date February 1, 2019
Submission Date January 22, 2019
Published in Issue Year 2019 Volume: 6 Issue: 1

Cite

APA Demirel, H., Baksın, E., Özgür, E. Ö., Topuz, R. D., et al. (2019). SYSTEMIC CANNABIDIOL DOES NOT REDUCE COMPOUND 48/80-INDUCED ITCHING BEHAVIOR IN MICE. Turkish Medical Student Journal, 6(1).
AMA Demirel H, Baksın E, Özgür EÖ, Topuz RD, Ulugöl A. SYSTEMIC CANNABIDIOL DOES NOT REDUCE COMPOUND 48/80-INDUCED ITCHING BEHAVIOR IN MICE. TMSJ. February 2019;6(1).
Chicago Demirel, Hatice, Elif Baksın, Ece Önay Özgür, Ruhan Deniz Topuz, and Ahmet Ulugöl. “SYSTEMIC CANNABIDIOL DOES NOT REDUCE COMPOUND 48/80-INDUCED ITCHING BEHAVIOR IN MICE”. Turkish Medical Student Journal 6, no. 1 (February 2019).
EndNote Demirel H, Baksın E, Özgür EÖ, Topuz RD, Ulugöl A (February 1, 2019) SYSTEMIC CANNABIDIOL DOES NOT REDUCE COMPOUND 48/80-INDUCED ITCHING BEHAVIOR IN MICE. Turkish Medical Student Journal 6 1
IEEE H. Demirel, E. Baksın, E. Ö. Özgür, R. D. Topuz, and A. Ulugöl, “SYSTEMIC CANNABIDIOL DOES NOT REDUCE COMPOUND 48/80-INDUCED ITCHING BEHAVIOR IN MICE”, TMSJ, vol. 6, no. 1, 2019.
ISNAD Demirel, Hatice et al. “SYSTEMIC CANNABIDIOL DOES NOT REDUCE COMPOUND 48/80-INDUCED ITCHING BEHAVIOR IN MICE”. Turkish Medical Student Journal 6/1 (February 2019).
JAMA Demirel H, Baksın E, Özgür EÖ, Topuz RD, Ulugöl A. SYSTEMIC CANNABIDIOL DOES NOT REDUCE COMPOUND 48/80-INDUCED ITCHING BEHAVIOR IN MICE. TMSJ. 2019;6.
MLA Demirel, Hatice et al. “SYSTEMIC CANNABIDIOL DOES NOT REDUCE COMPOUND 48/80-INDUCED ITCHING BEHAVIOR IN MICE”. Turkish Medical Student Journal, vol. 6, no. 1, 2019.
Vancouver Demirel H, Baksın E, Özgür EÖ, Topuz RD, Ulugöl A. SYSTEMIC CANNABIDIOL DOES NOT REDUCE COMPOUND 48/80-INDUCED ITCHING BEHAVIOR IN MICE. TMSJ. 2019;6(1).