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A2103
October 22, 2017
43030.416667 - 43030.5
Room Exhibit Hall B2 - Area E
Intrathecal TRPV1 Receptor Antagonist Reduced Morphine-induced Itch Without Hyperthermia in Mice
Satoshi Sakakibara, M.D., Noritaka Imamachi, M.D., Manabu Sakakihara, M.D., Yoji Saito, M.D.
Shimane University Faculty of Medicine, Izumo, Japan
Disclosures: S. Sakakibara: None. N. Imamachi: None. M. Sakakihara: None. Y. Saito: None.
Background: The mu-opioid receptor (MOR) agonist-induced itch is a significant side effect associated with analgesic therapies. We have not established the standard treatment of morphine-induced (central) itch in clinical. We have shown that Transient Receptor Potential Vanilloid 1 (TRPV1) plays an important role of histamine-induced (peripheral) itch1). However, it is not known whether TRPV1 effects on morphine-induced itch. On the other hands, systemic administration of TRPV1 antagonist causes hyperthermia2). Therefore, systemic administration of TRPV1 antagonist restricts in clinical uses. Here, we investigated effects of the low dose intrathecal TRPV1 antagonist on morphine-induced itch and antinociception in mice. We also studied effects of the low dose intrathecal TRPV1 antagonist on body temperature. Methods: With the approval of the Animal Care and Use Committee of our university, the studies were performed in male C57/ BL6 mice (21-27g). Experiment-1: Mice received intrathecal injections of one of the following drugs: morphine 0.1, 0.3, 1.0 nmol, TRPV1 antagonist SB366791 (SB) 0.01, 0.03, 0.1 nmol, the combination of morphine 0.3 nmol + SB 0.01, 0.03, 0.1 nmol, saline and vehicle (saline : ethanol = 9 : 1 ). Scratching behavior was videotaped for 60 min after intrathecal administration. Total numbers of scratches by the hind paws during the first 60 min after intrathecal injection were counted. Experiment-2: Mice received intrathecal injections of one of the following drugs: morphine 0.1, 0.3, 1.0 nmol, SB 0.01, 0.1 nmol, the combination of morphine 0.3 nmol + SB 0.1 nmol, saline and vehicle. The nociceptive threshold was determined by tail immersion test (48 ± 0.5 °C, cut off : 20 sec.). The test was performed before and 5, 15, 30, 60, 90, 120, and 150 min after the intrathecal injection. Experiment-3: Mice received intrathecal injections of one of the following drugs: morphine 0.3 nmol, SB 0.1 nmol, the combination of morphine 0.3 nmol + SB 0.1 nmol, saline and vehicle. The body temperature was measured by infrared thermometer at the back of mice before and 10, 20, 30, 40, 50 and 60 min after the intrathecal injection. Results were compared using repeated measures of ANOVA followed by Scheffe's test. Differences were considered to be significant at P < 0.05. Results: Experiment-1: Intrathecal morphine 0.3 nmol significantly increased scratching behavior compared with saline group. Intrathecal SB 0.1 nmol did not induce scratching behavior compared with vehicle group. Intrathecal SB dose-dependently reduced the scratching behavior induced by intrathecal morphine. The combination of morphine 0.3 nmol + SB 0.1 nmol group significantly reduced scratching behavior compared with morphine alone. (Fig.) Experiment-2: Intrathecal morphine dose-dependently produced antinociceptive effects. SB did not produce antinociceptive effects. The combination of morphine and SB did not augment morphine-induced antinociceptive effects. Experiment-3: The body temperature of mice was within 35.8-36.2°C between the all groups before and after the injection. Intrathecal SB did not significantly rise in body temperature compared with vehicle group. The combination of morphine + SB group did not significantly rise in body temperature compared with vehicle group neither. Conclusion: Our results suggested that the low dose intrathecal TRPV1 antagonist reduced morphine-induced itch without hyperthermia in mice. References: 1) PNAS. 2009; 106: 11330-11335 2) J Pharmacol Exp Ther. 2007; 323: 128-137



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