Role of Guanylyl Cyclase Activation via Thiamine in Suppressing Chemically-induced Writhing in Mouse

Abstract

The possible role of L-arginine/nitric oxide (L-arginine/NO) pathway in the antinociceptive activity of thiamine (vitamin B 1 ) in p-benzoquinone-induced mouse writhing model was investigated. Thiamine (ED 50 , 0.11 mg/kg), L-arginine (50 mg/kg), N G -nitro-L-arginine methyl ester (L-NAME, 75 mg/kg) and morphine (ED 50 : 0.13 mg/kg) displayed antinociceptions following s.c. administrations (52.4 ± 5.5 %, 36.8 ± 7.7 %, 27.8 ± 11.1 %, 66.1 ± 3.5 %, respectively). However, methylene blue (MB, 40 mg/kg, s.c.) produced a nociception (−32.1 ± 9.9 %). Coadministration of B 1 with L-arginine did not significantly change L-arginine-induced antinociception (48.9 ± 3.7 %). Cotreatment of thiamine with L-NAME and MB significantly increased the L-NAME-induced antinociception (53.9 ± 3.9 %) and reversed the MB-induced nociception to antinociception (46.0 ± 4.2 %). L-Arginine and L-NAME-induced antinociceptions were significantly increased (55.9 ± 3.9 % and 61.1 ± 5.0 %, respectively) by morphine. MB-induced nociception significantly reversed to antinociception by the concomitant administration of morphine (41.6 ± 8.9 %). Thiamine and morphine coadministration displayed antinociception (46.0 ± 4.2 %). The present results suggest that thiamine could produce antinociception by the activation of guanylyl cyclase mediated by cyclic guanosine monophosphate (cGMP) that may trigger the possible involvement of central and/or peripheral L-arginine/ NO/cGMP pathway. Zusammenfassung Die Rolle der Aktivierung von Guanylylcyclase bei der Unterdrückung des chemisch induzierten Writhing bei Mäusen mittels ThiaminZiel dieser Studie war es, die mögliche Rolle von L-Arginin/Stickoxid (L-Arginin/NO) bei der antinociceptiven Aktivität von Thiamin (Vitamin B 1 ) am p-Benzochinon-induzierten Maus-Writhing-Modell zu untersuchen. Thiamin (ED 50 : 0.11 mg/kg), L-Arginin (50 mg/kg), N G -Nitro-L-argininmethylester (L-NAME, 75 mg/kg) und Morphin (ED 50 : 0.13 mg/kg) zeigten bei s.c. Verabreichung eine schmerzlindernde Wirkung (52.4 ± 5.5 %, 36.8 ± 7.7 %, 27.8 ± 11.1 %, 66.1 ±3.5 %, in dieser Reihenfolge). Methylenblau (MB, 40 mg/kg, s.c.) verursachte dagegen eine gesteigerte Schmerzempfindung (−32.1 ± 9.9 %). Die Verabreichung von Thiamin mit L-Arginin zusammen änderte die durch L-Arginin induzierte Schmerzempfindung (48.9 ± 3.7 %) nur unwesentlich. Die Eingabe von Thiamin mit L-NAME und MB zusammen erhöhte die durch L-NAME induzierte schmerzlindernde Wirkung (53.9 ± 3.9 %) signifikant und kehrte die durch MB induzierte Schmerzempfindung zur Schmerzlinderung um (46.0 ± 4.2 %). Gleichzeitige Gabe mit Morphin erhöhte deutlich den durch L-Arginin und L-

The Role of L-Arginine/Nitric Oxide Pathway in the Antinociceptive Activity of Pyridoxine in Mouse

“…The results of the present study indicate that exogenous (s.c.) administrations of the agents which have modulatory effects on L-arginine/NO/cGMP pathway modify pyridoxine-induced antinociception in mice in contrast to our previous findings with another B complex vitamin, thiamine [24].…”

“…It is also known that L-arginine is metabolized via the nitric oxide synthase (NOS) to form nitric oxide (NO), which is a messenger in the central and peripheral nociceptive processing individually or [18−21] and citrulline or via arginase to produce urea and Lornithine is further metabolized to polyamines by PLPinduced coenzymatic synthesis and L-proline [22,23]. We have previously shown that another B group vitamin, thiamine (vitamin B 1 ) produces antinociceptive effect by the possible involvement of a central and/or peripheral L-arginine/NO/cGMP pathway in the pbenzoquinone (PBQ)-induced abdominal constriction test in mice [24].…”

Role of L-Arginine/Nitric Oxide Pathway in the Antinociceptive Activities of Morphine and Mepyramine in Mice

“…In this study, morphine significantly reduced PBQinduced abdominal constrictions as previously shown [22,35] and the NO precursor L-arginine also significantly increased morphine-induced analgesia in contrast to findings of Bian and Bhargava [43] and Contreras et al [44]. On the other hand, our results are in agreement with those of Brignola et al [45] who suggested that the L-arginine/NO pathway modulates both the central and peripheral antinociceptive effects of morphine and this modulation seems to take place at peripheral sites.…”

“…of PBQ at a dose of 2.5 mg/kg caused abdominal constriction in all control animals. Mepyramine (ED 50 : 5.6 mg/kg) [22], morphine (ED 50 : 0.13 mg/ kg) [22], L-arginine 50 mg/kg [35] and L-NMMA (50 mg/ kg) were injected alone and in combinations s.c. half an hour before the injection of PBQ and the solutions were adjusted to make an injection volume of 0.1 ml per 10 g of mouse. The experiments were performed at room temperature (20−22°C).…”

“…The normally distributed percent protection (% antinociceptive activity) at each dose level was calculated and normalised as follows for individual mouse: % protection = ARCSIN Ί [100 -(E / C) × 100] where E and C represents experimental, and control counts of constriction values respectively [13,35,36].…”