Morphine antinociception has been shown to be influenced significantly by genetic factors, now beginning to be identified in mice. A recent quantitative trait locus analysis revealed a significant statistical association between morphine antinociceptive magnitude and a region of mouse chromosome 9. This region contains the Htr1b gene, which encodes the 5-hydroxytryptamine (serotonin)-1B (5-HT(1...

Fentanyl has been shown to be a potent analgesic with a lower propensity to produce tolerance and physical dependence in the clinical setting. The present study was designed to investigate the mechanisms of fentanyl- or morphine-induced antinociception at both supraspinal and spinal sites. In the mouse tail-flick test, the antinociceptive effects induced by both fentanyl and morphine were block...

Studies in mice and rats have shown that antinociception produced by intrathecal (i.t.) administration of opioids can be partially inhibited by intracerebroventricular (i.c.v.) administration of naloxone. In this study we tested the hypothesis that this inhibition by i.c.v. naloxone results from antagonism of supraspinal endogenous opioid-mediated antinociception produced by the action of i.t. ...

UNLABELLED Antinociception can be produced at the spinal level by activation of opioidergic, noradrenergic, and serotonergic systems. We tested the antinociceptive effects of combined activation of all three systems. Antinociception was assessed in the rat tail-flick test, and drugs were administered via an intrathecal catheter. Morphine, the norepinephrine uptake inhibitor desipramine, and ser...

Some antiepileptic drugs have been shown to be clinically effective in the treatment of neuropathic pain. This study determined whether the new antiepileptic drug tiagabine, a GABA uptake inhibitor, is efficacious in mice in a broad range of nociceptive tests (hot-plate, formalin, and dynorphin-induced chronic allodynia) and compared tiagabine's potency with two other antiepileptic drugs, gabap...

The analgesia produced by inhibitory G protein-coupled receptor agonists involves coordinated postsynaptic inhibition via G protein-coupled inwardly rectifying potassium channels (GIRKs) and presynaptic inhibition of neurotransmitter release through regulation of voltage-gated Ca(2+) channels. Here, we used mice lacking the GIRK2 channel subunit to assess the relative contribution of these two ...

When coadministered spinally, morphine and clonidine interact synergistically to produce antinociception. The mechanism for the synergism is unknown, but may depend on intracellular messenger systems. Agents that alter the activities of protein kinases alter antinociception produced by opioids, but their effects on clonidine-induced antinociception or the morphine/clonidine interaction are not ...

Ingestion of placenta or amniotic fluid produces a dramatic enhancement of centrally mediated opioid antinociception in the rat. The present experiments investigated the role of each opioid receptor type (A, y, n) in the antinociception-modulating effects of Placental Opioid-Enhancing Factor (POEF—presumably the active substance). Antinociception was measured on a 52 jC hotplate in adult, femal...

Endogenous opioids have been implicated in compound-induced antinociception, and our group previously suggested that xylazine induces peripheral antinociception by releasing endogenous opioids that act on their respective receptors. In this study, we investigated the involvement of endogenous opioids in α2-adrenoceptor agonist xylazine-induced central antinociception. The nociceptive threshold ...

this study was designed to investigate the role of gabab receptor agents on imipramine-induced antinociception in ligated and non-ligated mice using hot-plate test. the data showed that different doses of morphine (3, 6, and 9 mg/kg) induced a dose-dependent antinociception in ligated and non-ligated mice. however, the opioid response was decreased in ligated animals. intracerebroventricular (i...