In the present study, the antinociceptive profiles of coumarin were examined in ICR mice. Coumarin administered orally (from 1 to 10 mg/kg) showed an antinociceptive effect in a dose-dependent manner as measured in the acetic acid-induced writhing test. Duration of antinociceptive action of coumarin maintained at least for 60 min. But, the cumulative response time of nociceptive behaviors induc...

Dynorphin A (Dyn A) is an endogenous opioid ligand that possesses neuroinhibitory (antinociceptive) effects via μ, δ, and κ opioid receptors. However, under chronic pain conditions, up-regulated spinal Dyn A can also interact with bradykinin receptors (BRs) to promote hyperalgesia through a neuroexcitatory(pronociceptive) effect. These excitatory effects cannot be blocked by an opioid antagonis...

BACKGROUND Intrathecal morphine-induced pruritus is a very common side-effect that is difficult to prevent or treat. Central and peripheral mechanisms are believed to be involved. The aim of this study was to determine if a peripherally acting, μ-opioid antagonist would reduce morphine-induced pruritus. METHODS We conducted a multicentre, randomized, blinded, placebo-controlled trial of women...

To determine the role of spinal mu-opioid receptor subtypes in antinociception induced by intrathecal (i.t.) injection of endomorphin-1 and -2, we assessed the effects of beta-funaltrexamine (a selective mu-opioid receptor antagonist) naloxonazine (a selective antagonist at the mu(1)-opioid receptor) and a novel receptor antagonist (3-methoxynaltrexone) using the paw-withdrawal test. Antinocice...

Itch/pruritus is the most common side effect associated with spinal administration of morphine given to humans for analgesia. The aim of this study was to investigate the effectiveness of -opioid receptor (KOR) agonists with diverse chemical structures as antipruritics and to elucidate the receptor mechanism underlying the antipruritic effect in monkeys. In particular, previously proposed non-K...

The development of opioid-induced analgesic tolerance and hyperalgesia is a clinical challenge for managing chronic pain. Adaptive changes in protein translation in the nervous system are thought to promote opioid tolerance and hyperalgesia; however, how opioids drive such changes remains elusive. Here, we report that mammalian target of rapamycin (mTOR), which governs most protein translation,...

Objective: Intrathecal morphine (ITM) is an effective postoperative analgesia provided after Cesarean section. However, pruritus undesirable side effect that disrupts maternal breast feeding. This study aimed to evaluate the effects of three different doses ITM added spinal bupivacaine on and opioid-related in Material Methods: prospective randomized, triple-blinded trial was conducted 321 pati...

DALDA (H-Tyr-D-Arg-Phe-Lys-NH(2)) and [Dmt(1)]DALDA (H-Dmt-D-Arg-Phe-Lys-NH(2)) (Dmt = 2',6'-dimethyltyrosine) are potent and highly selective mu-opioid agonists (K(i)(delta)/K(i)(mu) > 10,000 and K(i)(kappa)/K(i)(mu) > 100). Both peptides carry a 3+ charge at physiological pH. Their antinociceptive and respiratory effects were compared with morphine (MOR) after intrathecal administration in ra...

Itch/pruritus is the most common side effect associated with spinal administration of morphine given to humans for analgesia. The aim of this study was to investigate the effectiveness of kappa-opioid receptor (KOR) agonists with diverse chemical structures as antipruritics and to elucidate the receptor mechanism underlying the antipruritic effect in monkeys. In particular, previously proposed ...

Editor,—Buerkle and colleagues report that intrathecal administration of remifentanil in rats that had received intraplantar formalin could wholly abolish nociceptive behaviour during phase 1 of the formalin test but was associated with only partial inhibition of glutamate release as measured by microdialysis.1 Intraplantar injection of formalin results in a biphasic behavioural response, the s...