Journal Club 18.02.09.
Pharmacological evidence of involvement of nitric oxide pathway in anti-pruritic effects of sumatriptan in chloroquine-induced scratching in mice
Nazgol-Sadat Haddadia,b, Sattar Ostadhadia,b,c, Saeed Shakibaa,b, Khashayar Afsharia,b, Nastaran Rahimia,b, Arash Foroutana,b, Ahmad-Reza Dehpoura,b* aExperimental Medicine Research Center, Tehran University of Medical Sciences, Poorsina St., Enghelab Ave., Tehran, Iran bDepartment of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Poorsina St., Enghelab Ave., Tehran, Iran cBrain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Chamran highway, Bagherkhan St., Imam Khomeini Hospital, Tehran, Iran
Chloroquine (CQ) induces histamine-independent itch in human and mice. We recently reported the role of intradermal nitric oxide (NO)/cyclic guanosine monophosphate pathway in CQ-evoked scratching in mice. Chloroquine stimulates neuronal nitric oxide synthase (nNOS) activity to over-producing NO in the skin. Sumatriptan, a 5-hydroxytryptamine 1b/1d receptors (5-HTR1b/1d) agonist, is involved in pain and used to treat migraine and cluster headaches. According to previous studies, sumatriptan inhibits NOS activity. Thus, we aimed to investigate the effect of sumatriptan on CQ-induced scratching. We used the rostral back model of itch. Chloroquine was injected intradermally into the rostral back of NMRI mice, and the scratching behavior was evaluated by measuring the number of bouts over 30 min. We evaluated the effect of sumatriptan and combination of sumatriptan and a non-selective NO synthase inhibitor, L-N-nitro arginine methyl ester (L-NAME), on the scratching behavior. Additionally, the changes of skin, hip- pocampus, and cortical nitrite level after different treatments were studied. Intraperitoneal and intradermal sumatriptan attenuates CQ-induced itch which reversed by GR-127935, the selective 5-HTR1b and 5-HTR1d antagonist. Co- administration of subeffective doses of sumatriptan and L-NAME significantly decreases the scratching behavior. Intradermal injection of CQ significantly increases the intradermal nitrite levels while it does not have any significant effects on hippocampal or cortical nitrite concentrations. Likewise, the effective doses of intraperitoneal and intradermal sumatriptan significantly reduce intradermal nitrite levels. We concluded that sumatriptan suppresses CQ-induced itch most likely by activating 5-HT1b/1d receptors. This effect probably mediates through NO pathway.