Morphine In Formalin Test Research Articles

Orexin receptor type-1 antagonist SB-334867 decreases morphine-induced antinociceptive effect in formalin test

Orexin-A and orexin-B are two neuropeptides selectively synthesized in the lateral hypothalamus (LH), a region involved in morphine induced analgesia and pain modulation. Furthermore, orexin-A has been reported to produce an analgesic effect in pain models, which was blocked by orexin-1 receptor antagonist SB-334867, but not naloxone. We studied the effects of intracerebroventricular (ICV) injection of SB-334867, a selective orexin receptor type-1 antagonist, on morphine-induced antinociceptive effect in formalin test in rats. Morphine injection at a dose of 1.5mg/kg caused a significant decrease in the formalin-induced nociceptive behaviors in phase 1, interphase, and phase 2A, whereas at doses of 3, 6, and 10mg/kg, a significant reduction in the formalin-induced nociceptive behaviors was observed in all phases. The ICV injection of SB-334867 alone had no effect on the formalin-induced nociceptive behaviors. Pre-treatment with SB-334867 at a dose of 0.5nmol significantly attenuated the analgesia induced by morphine (at dose 1.5mg/kg of morphine; interphase and phase 2B and at dose 3mg/kg of morphine just phase 2B of formalin test). Also, pre-treatment with SB-334867 at a dose of 5nmol considerably attenuated the morphine-induced analgesia (at dose 1.5mg/kg of morphine; phase 1, interphase, and phase 2, at dose 3 and 6mg/kg of morphine just phase 2 of formalin test). Pre-treatment with SB-334867 at a dose of 50nmol remarkably attenuated the morphine-induced analgesia (at dose 1.5 and 3mg/kg of morphine; in phase 1, interphase, and phase 2 and also at dose 6mg/kg of morphine; phase 1 and phase 2B of formalin test). These data suggest that the antinociceptive effects of morphine in formalin test might be associated with orexin receptor type-1. Our findings reveal a new role for the lateral hypothalamus orexin neurons in the morphine-induced analgesia.

Effects of L-NAME on Antinociceptive Induced by Morphine in Formalin Test

Effects of L-NAME on Antinociceptive Induced by Morphine in Formalin Test

Cross-tolerance between antinociception induced by swim-stress and morphine in formalin test

The present study investigated cross-tolerance between antinociception induced by water swim-stress and morphine in the formalin test. Intraperitoneal administration of morphine (3, 6 and 9 mg/kg) induced dose-dependent antinociception in both phases of the formalin test. Mice treated with a lower dose of morphine (25 mg/kg), once daily for 3 days, showed tolerance to antinociception induced by a lower test dose of morphine (3 mg/kg). Similar repeated treatments with a higher dose of morphine (50 mg/kg) produced tolerance to antinociception induced by different test doses of morphine (3, 6 and 9 mg/kg). Exposure to water swim-stress, once daily for 2 or 3 days in order to induce tolerance, also decreased morphine-induced antinociception. Swim-stress exposure for 2 or 3 days also tends to potentiate tolerance induced by a lower dose of morphine. Acute swim-stress of different durations (0.5, 1 and 3 min) induced antinociception in both phases of the formalin test, which was not reduced by naloxone, but showed even more antinociception in the second phase. The response to swim stress was decreased in mice treated with higher doses of morphine, but not those animals that received swimming stress (3 min) once daily for 2-3 days, in order to induce habituation to swim-stress-induced antinociception. The results may indicate a possible cross-tolerance between antinociception induced by morphine and by swim stress.

Effects of morphine on formalin-induced nociception in rats

This study focused on the antinociceptive action of morphine in the formalin test in rats. Formalin-induced behaviour is characterised by two phases relevant to acute and tonic pain. Morphine (1–6 mg/kg) was administered systemically before or after the early phase, and its ability to affect the late phase was investigated. Inhibitory effects of morphine (3 mg/kg) injected immediately after the early phase were significantly stronger (32±9%) compared to the preemptive administration (84±29%, relative to saline-treated controls, 5% formaldehyde). It appears that some neural and/or behavioural changes during the early phase limit effects of morphine on the late phase. Furthermore, manipulation of stimulation intensity (2% vs. 5% formaldehyde) significantly affected the ability of morphine (3 mg/kg) to suppress early (55±7% and 76±10%, respectively) but not late phase of formalin-induced behaviours. These results agree with the previous demonstrations on the effects of acute nociceptive stimulation intensity on analgesic potency of opiate drugs. Thus, the present study revealed two factors that affect the potency of morphine in formalin test: administration regimen and formalin concentration.

Effects of intraplantar morphine in the mouse formalin test.

We studied the effects of intraplantar morphine in the formalin test in mice. Intraplantarly administered morphine (30 - 300 microg) induced analgesic effects at lower doses than intraperitoneally administered morphine. Following the administration of [3H]morphine, the % of radioactivity present in brain was the same by either route. In contrast, higher radioactivity values appeared in the injected paw in those mice intraplantarly injected. Since local morphine induces analgesia at doses lower than the intraperitoneally administered drug, especially in the second phase of the test, and the access to brain is undistinguishable, we propose that local morphine enhances central opiate analgesia in the formalin test in mice.

Lack of antinociceptive activity of clonidine in two pain models: Comparison with other analgesics and CNS active drugs

AbstractThe antinociceptive activity of clonidine was investigated in two models of pain using the modified Haffner tail clip test (MHA) in mice and the formalin test (FT) in rats. Morphine was used as a positive control for comparison. Clonidine at does from 0.5 mg/kg to 8 mg/kg SC was not effective in MHA while morphine administration resulted in a dose‐dependent increase in the latency to bite the clip and an ED50 of 1.2 mg/kg SC. No antinociceptive activity was observed for clonidine using the FT up to a dose of 4 mg/kg SC which causes severe behavioral depression. The ED50 for morphine in FT was 1.7 mg/kg SC. From these studies we conclude that clonidine is not active in all tests used to predict analgesic efficacy in man. Additional analgesic and centrally acting drugs were also included for comparative purposes. Of the compounds tested only the opiates active in FT and MHA and cholinesterase inhibitors (active in MHA only) showed analgesic effects.