Antinociception In Formalin Test Research Articles

Intra-paragigantocellularis lateralis injection of orexin-A has an antinociceptive effect on hot plate and formalin tests in rat

In the present study, the effect of orexin-A (ORXA) microinjection into the paragigantocellularis lateralis (LPGI) on nociceptive behaviors, using hot-plate and formalin tests as thermal and chemical models of pain in rat, was examined. Also, we determined whether the pretreatment with SB-334867, a selective OX1-receptor antagonist, would prevent the antinociceptive effect of orexin-A. ORXA (0.1–100nM/0.5μL) microinjected into the LPGi nucleus, dose-dependently decreased the formalin induced nociceptive behaviors and also produced a dose-dependent antinociceptive effect in the hot-plate test. Pretreatment with a selective orexin receptor 1 (OX1R) antagonist, SB-334867, also inhibited the effect of ORXA on formalin induced nociceptive behaviors while the SB-334867 (100μM) alone had no effect on formalin test. These data demonstrated that the ORXA-induced antinociception in formalin test is mainly mediated through the OX1R in LPGi which might play a potential role in processing the pain information associated with descending pain modulation.

μ but not δ and κ opioid receptor involvement in ventrolateral orbital cortex opioid-evoked antinociception in formalin test rats

The present study was designed to investigate the roles of different subtypes of opioid receptors in ventrolateral orbital cortex (VLO) opioid-evoked antinociception in formalin test by using an automatic detection system for recording the nociceptive behavior (agitation) and a manual method for detecting the duration of licking the injected paw in the conscious rat. Formalin (5%, 50 μl) s.c. injected into the hindpaw produced a biphasic agitation response or lengthening duration of licking. Morphine (5 μg) microinjected unilaterally into VLO significantly inhibited the agitation response and the licking time, and these effects were blocked by pre-administration of the non-selective opioid receptor antagonist naloxone (1.0 μg) into the same site. Microinjection of endomorphin-1 (5 μg), a selective μ-receptor agonist, and [ d-Ala 2, d-Leu 5]-enkephalin (DADLE, 10 μg), a δ-/μ-receptor agonist also inhibited the nociceptive behaviors, and both the effects were blocked by selective μ-receptor antagonist β-funaltrexamine hydrochloride (β-FNA; 3.75 μg), but the DADLE-evoked inhibition was not influenced by the selective δ-receptor antagonist naltrindole (5 μg). Microinjection of selective κ-receptor agonist (±)- trans-U-50488 methanesulfonate salt (1.5 μg) failed to alter the nociceptive behaviors induced by formalin injection. The β-FNA and naloxone applied into VLO and morphine into the adjacent regions ventral and dorsal to VLO had no effect on the formalin-evoked nociceptive behaviors. These results suggest that μ- but not δ- or κ-opioid receptor is involved in the VLO opioid-evoked antinociception in formalin test rat.

Pretreatment with cholera or pertussis toxin differentially modulates morphine- and bβ-endorphin-induced antinociception in the mouse formalin test

The present study was designed to examine the possible involvement of supraspinal CTX- and PTX-sensitive G-proteins in an opioid-induced antinociception in the formalin test. Morphine (1μg) and β-endorphin (1μg) given i.c.v. displayed near-maximal inhibitory effects against the formalin response in the first (0–5min) and the second (20–40min) phases. CTX (0.1–0.5μg) pretreated i.c.v. produced antinociceptive effects in both phases of the formalin responses. Its effect was more pronounced in the first phase. However, PTX (0.05–0.5μg) injected i.c.v produced the antinociceptive effect only in the first, but not the second, phase. Both CTX (0.5μg) and PTX (0.5μg), at the dose which had no intrinsic effect, significantly reversed the β-endorphin-induced antinociceptive effect observed during the second, but not the first, phase. However, the antinociceptive effect by morphine failed to be affected by the same dose of treatment with CTX or PTX. Our results indicate that, at the supraspinal level, CTX- and PTX-sensitive G-proteins appear to be involved in the modulation of antinociception induced by supraspinally administered β-endorphin, but not morphine, in the formalin pain model.

Baclofen and antidepressant--induced antinociception in formalin test: possible GABA(B) mechanism involvement.

In this study, the influences of GABA(B) agents on antidepressant-induced antinociception in the mouse formalin test have been investigated. The GABA(B) receptor agonist baclofen (2.5, 5 and 10 mg/kg) induced a dose-dependent antinociception in the second phase of the formalin test. This response was inhibited by the GABA(B) receptor antagonist, CGP35348 [P-(3-aminopropyl)-p-diethoxymethyl-phosphinic acid], in a dose-dependent manner. The antagonist by itself also induced antinociception. Single administration of the antidepressants citalopram (10, 20, 40 and 80 mg/kg), desipramine (20, 40, 80 mg/kg) or imipramine (10, 20 and 40 mg/kg) also induced antinociception in both phases of the formalin test. CGP35348 (100 and 200 mg/kg) pretreatment reduced the response induced by the tricyclic antidepressants. A combination of baclofen with the tricyclic antidepressant did not potentiate antinociception induced by antidepressants, but a decrease in the response induced by higher dose of baclofen was shown. It is concluded that GABA mechanism(s) may modulate the antidepressant-induced antinociception.