The antinociceptive effects of histidyl-proline diketopiperazine and thyrotropin-releasing hormone in the mouse

https://doi.org/10.1016/0014-2999(85)90774-5Get rights and content

Abstract

Intracerebroventicular (i.c.v.) injection of histidyl-proline diketopiperazine [cyclo (His-Pro)], an active metabolite of thyrotropin-releasing hormone (TRH) in mice produced an antinociceptive effect in a dose-dependent manner as measured in four antinociceptive tests; tail-pressure, tail-flick, hot-plate and acetic acid writhing. The antinociceptive effect of cyclo (His-Pro) reached a maximum at 5 min and lasted for 30 min. The ED50 values for the tests were 760.0 (598.4–965.2), 540.0 (442.6–658.8), 595.0 (487.7–725.9) and 370.0 (286.8–477.3) nmol/mouse and the slope functions were 1.61, 1.56, 1.57 and 1.66, respectively. Pretreatment with naloxone (0.5, 2 and 8 mg/kg), an opioid antagonist, administered subcutaneously antagonized the antinociceptive effect of cyclo (His-Pro). TRH injected i.c.v. to mice also exerted a dose-dependent antinociceptive action as measured in three antinociceptive tests; tail-pressure, hot-plate and acetic acid writhing. The antinociceptive effect of TRH was only seen at 5 min. The ED50 values for each test were 112.0 (47.5–264.3), 19.2 (10.4–35.5) and 0.2 (0.1–0.4) nmol/mouse and the slope functions were 8.89, 4.14 and 3.94, respectively. TRH was without effect in the tail-flick test. In contrast to cyclo (His-Pro), TRH-induced antinociception was not antagonized by pretreatment with naloxone (0.5, 2 and 8 mg/kg). The data suggest that the two peptides have a different mechanism of antinociceptive action in relation in the involvement of the opioid system in the central nervous system.

References (36)

Cited by (17)

  • Taltirelin, a thyrotropin-releasing hormone analog, alleviates mechanical allodynia through activation of descending monoaminergic neurons in persistent inflammatory pain

    2011, Brain Research
    Citation Excerpt :

    Previous studies showed that TRH and its analog taltirelin have antinociceptive effects in mice under normal conditions, mainly via supraspinal actions. For examples, intracerebroventricular administration of TRH and its metabolite significantly attenuated acute pains induced by pressure and heat stimulation (Kawamura et al., 1985). Tanabe et al. (2007) also demonstrated that subcutaneous or intracerebroventricular injection of taltirelin exerted antinociceptive effects by activating the descending noradrenergic and serotonergic pain inhibitory systems, while blocking the opioid system with naloxone did not alter antinociceptive effect of taltirelin.

View all citing articles on Scopus
View full text