Antinociceptive properties of thyrotropin releasing hormone in mice: comparison with morphine.

1 To investigate the antinociceptive activity of thyrotropin releasing hormone (TRH) in mice, different nociceptive stimuli were used. TRH (i.p.) was active in the phenyl-p-benzoquinone or acetic acid-induced writhing tests (chemical stimuli) and in Haffner's test (mechanical stimulus); its action decreased rapidly 15 min after intraperitoneal injection. 2 To determine whether the activity of TRH has a peripheral or central origin, we administered TRH intracerebroventricularly via cannulae previously implanted in mice. The results provide evidence that a central mechanism is involved in the analgesic effect of TRH since when given intracerebroventricularly it was 10,000 and 1,000 times more active against chemical and mechanical stimuli respectively than intraperitoneally. The action of TRH decreased rapidly 5 min after i.c.v. injection. Morphine was studied in these tests and it was found that at the peak effect TRH analgesia (i.c.v.) was greater than that of morphine (i.c.v.) on a molar basis. 3 To investigate the mechanisms involved in the antinociceptive action of TRH, the effects of pretreatment with either agonists or antagonists of noradrenaline (NA), dopamine and 5-hydroxytryptamine (5-HT), or naloxone were studied. TRH activity was generally resistant to modifications of NA, dopamine and 5-HT systems. The TRH effect was not antagonized by naloxone, but TRH at a non-analgesic dose presented the hyperalgesia induced by naloxone. 4 In conclusion, TRH i.c.v. possessed a short, strong antinociceptive activity against chemical and mechanical stimuli. This analgesia was at least equipotent to that of morphine i.c.v.