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


CONCLUSIONS
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.
Department of Medical Pharmacology, Faculty of Medicine,Trakya University,22030-Edirne,Turkey.
Zeynep Gizem
ZG
Todurga
Department of Medical Pharmacology, Faculty of Medicine,Trakya University,22030-Edirne,Turkey.
Ozgur
O
Gunduz
Department of Medical Pharmacology, Faculty of Medicine,Trakya University,22030-Edirne,Turkey.
Cetin Hakan
CH
Karadag
Department of Medical Pharmacology, Faculty of Medicine,Trakya University,22030-Edirne,Turkey.
Ahmet
A
Ulugol
D015116:5,7-Dihydroxytryptamine / Q000008:administration & dosage; D000818:Animals; D000982:Antipruritics / Q000008:administration & dosage*; D048588:Benzoxazines / Q000008:administration & dosage*; D063386:Cannabinoid Receptor Agonists / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008807:Mice, Inbred BALB C; D009025:Morpholines / Q000008:administration & dosage*; D009281:Naphthalenes / Q000008:administration & dosage*; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D009638:Norepinephrine / Q000502:physiology*; D016627:Oxidopamine / Q000008:administration & dosage; D011537:Pruritus / Q000139:chemically induced / Q000503:physiopathology*; D012701:Serotonin / Q000008:administration & dosage / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology
D000982:Antipruritics; D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D009025:Morpholines; D009281:Naphthalenes; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D016627:Oxidopamine; D009638:Norepinephrine
212-2; WIN 55; cannabinoid system; descending inhibition; pruritus