Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · Jan 2005
Comparative StudyInvolvement of potassium channels and nitric oxide in tramadol antinociception.
It has been considered that tramadol, a centrally acting analgesic, shows its effect via opiatergic, noradrenergic, and serotonergic systems. It has a low affinity for opioid receptors, and its effect can be partly blocked by naloxone. Since the noradrenergic and serotonergic mechanisms are still unknown, other systems which are associated with pain and analgesia may have a role on the antinociceptive effect of tramadol. ⋯ However, L-NAME augmented the antinociceptive effect of tramadol. The reduction of the effects of tramadol by L-arginine was reversed by L-NAME. The results of our study suggest that nonspecific voltage-dependent K+ channels and nitrergic system have a role on the antinociceptive effect of tramadol in mice hot plate test.
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Pharmacol. Biochem. Behav. · Jan 2005
Comparative StudyComparison of five different rat models of peripheral nerve injury.
Described here is a comparison of five peripheral sciatic nerve injury models in rats which all result in various degrees of neuropathic pain symptoms. They are the chronic constriction injury (CCI), the spinal nerve ligation (SNL), the partial sciatic ligation (PSL), the tibial and sural transection (TST), and the complete sciatic transection (CST) model. ⋯ Overall, all five models of neuropathic pain produced signs of allodynia and hyperalgesia to various stimuli. However, the duration and magnitude of the evoked responses varied considerably between the different models.
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Pharmacol. Biochem. Behav. · Oct 2004
Dopaminergic mechanisms in the conditioned and unconditioned fear as assessed by the two-way avoidance and light switch-off tests.
The involvement of dopaminergic mechanisms in fear and anxiety is still unclear. Behavioral studies aimed to disclose the involvement of dopamine in anxiety have reported anxiolytic-like, anxiogenic-like and lack of effects with the use of dopaminergic agonists and antagonists in animal models of anxiety. This work was an attempt to contribute to this field by providing evidence that these discrepancies may be due to the kind of aversive situation the animals experience in these models. ⋯ Thus, blockade of D(1) and D(2) receptors may be necessary for attenuating the aversiveness triggered by these conditioned fear stimuli. In contrast, mechanisms mediated by D(2) receptors seem to be involved in the setting up of adaptive responses to innate fear reactions. Therefore, the signal of the modulatory dopaminergic mechanisms on defensive behavior will depend on the type of emotional stimuli triggering the coping reaction.
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Pharmacol. Biochem. Behav. · Jun 2004
Randomized Controlled Trial Comparative Study Clinical TrialLack of effect of two oral sodium channel antagonists, lamotrigine and 4030W92, on intradermal capsaicin-induced hyperalgesia model.
Preclinical studies have emphasized that persistent small afferent input will induce a state of central facilitation, which can be regulated by systemically administered sodium channel blockers. We have extended these preclinical studies to the human volunteers by examining the effects of lamotrigine and 4030W92, two structurally related voltage-sensitive sodium channel antagonists, on acute sensory thresholds and facilitated processing induced by intradermal capsaicin. Fifteen healthy subjects received 4030W92, lamotrigine, and placebo in a randomized order using double-blinded crossover design methodology in three sessions each separated by a 7-day washout period. ⋯ Similarly, oral lamotrigine or 4030W92 did not alter the pain scores reported from mechanical pain stimuli at any time postcapsaicin. This study showed a lack of effect of two structurally similar sodium channel antagonists on a human experimental pain model using intradermal capsaicin, which is consistent with other studies on the effects of sodium channel antagonists of capsaicin-induced pain and hyperalgesia. This lack of effect stands in contrast to reported effects of sodium channel antagonists on preclinical models of cutaneous hyperalgesia or effects of lamotrigine on clinical neuropathic pain.
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Pharmacol. Biochem. Behav. · Apr 2004
Comparative StudyNefopam potentiates morphine antinociception in allodynia and hyperalgesia in the rat.
The objective of this study was to resolve discrepancies regarding the possible antinociceptive synergy between morphine and nefopam in animal models of pain. Firstly, we have examined the antinociceptive activity of nefopam, a nonopioid antinociceptive compound that inhibits monoamine reuptake, in pain models of allodynia and hyperalgesia induced by carrageenan injection, or skin and muscle incision of the rat hind paw. Single subcutaneous administration of nefopam at 30 mg/kg blocked carrageenan- and incision-induced thermal hyperalgesia, and weakly but significantly diminished carrageenan-induced tactile allodynia. ⋯ Combination of a nonanalgesic dose of nefopam (10 mg/kg) with a nonanalgesic dose of morphine (0.3 or 1.0 mg/kg) completely inhibited carrageenan- or incision-induced thermal hyperalgesia, respectively. In carrageenan-induced tactile allodynia, coadministration of weak analgesic doses of nefopam (10 and 30 mg/kg) with a nonanalgesic dose (1 mg/kg) or moderately analgesic dose (3 mg/kg) of morphine significantly reduced or reversed allodynia, respectively. In conclusion, coadministration of nefopam with morphine enhances the analgesic potency of morphine, indicating a morphine sparing effect of nefopam.