The nitric oxide synthase inhibitor NG-nitro-L-arginine (NO2Arg) blocks morphine tolerance in mice. After implantation of pellets the analgesic response decreases from 100% on first day to 0% third. Coadministration NO2Arg along with markedly retards development tolerance; 60% mice are after 3 days, and 50% 5 days. In a daily injection paradigm is reduced by Concomitant administration at doses 2 mg/kg per prevents for 4 weeks. A single dose several dosing every days almost as effective...

Once daily s.c. administration of 5 mg/kg morphine, a mu-opioid agonist, or U50488H (U50), kappa 1-opioid for days in male CD-1 mice results 2-3-fold shift to the right respective analgesic (tail flick) dose-response curves, indicating development tolerance. Concurrent competitive NMDA receptor antagonist, LY274614 (LY), at 24 mg/kg/24 h infusion (osmotic pump) 6 i.p. once attenuates morphine tolerance, when response saline plus is compared on day with LY morphine. Using this paradigm,...

Administered alone, agmatine at doses of 0.1 or 10 mg/kg is without effect in the mouse tailflick assay. However, enhances morphine analgesia a dose-dependent manner, shifting morphine's ED50 over 5-fold. A far greater observed when given intrathecally (9-fold shift) than after intracerebroventricular administration (2-fold). In contrast to potentiation analgesia, (10 mg/kg) has no on inhibition gastrointestinal transit. δ-Opioid receptor-mediated also potentiated by agmatine, but...

Previous studies have generated controversial results regarding the influence of genetic variations μ-opioid receptors on morphine analgesia and opioid-related side effects in postoperative period. Few been conducted attempting to assess combined variation within ≥2 genes relation response. In this study, we investigated whether catechol-O-methyltransferase receptor polymorphisms contribute response analgesia.One hundred two surgical patients were enrolled prospective, observational study....

Several isoforms of neuronal nitric oxide synthase (nNOS) have been identified. Antisense approaches developed which can selectively down-regulate nNOS-1, corresponds to the full-length nNOS originally cloned from brain, and nNOS-2, a truncated form lacking two exons is generated by alternative splicing, as demonstrated decreases in mRNA levels. treatment also lowers enzymatic activity. Down-regulation nNOS-1 prevents development morphine tolerance. Whereas analgesia lost control...

Morphine injected s.c. in the tail is a potent analgesic tail-flick assay when radiant heat source focused directly over injection site (ED50, 4.5 micrograms), but not if moved 1 cm proximally or distally to site. Naloxone given systemically reverses this peripheral analgesia. Antisense oligodeoxynucleotides directed against exons and 4 of MOR-1, cloned mu opioid receptor, administered intrathecally (i.t.) block local effect morphine tail, indicating that response mediated through receptors...

The blood-brain barrier restricts the passage of substances into brain. Neuropeptides, such as enkephalins, cannot be delivered brain when given systemically because this barrier. Therefore, there is a need to develop efficient transport systems deliver these drugs Recently, we have demonstrated that conjugation doxorubicin or penicillin peptide vectors significantly enhances their uptake. In study, conjugated enkephalin analog dalargin with two different vectors, SynB1 and SynB3, improve...

Preoperative pain, type of operation and anesthesia, severity acute postoperative psychosocial factors have been identified as risk for chronic postsurgical pain (CPP). Recently, it has suggested that genetic also contribute to CPP. In this study, we aimed determine whether the catechol-O-methyl transferase (COMT) opioid receptor μ-1 (OPRM1) common functional polymorphisms rs4680 rs1799971 were associated with incidence, intensity, or duration CPP in patients after lower abdominal...

In addition to its central actions, morphine has important peripheral effects. To examine analgesic mechanisms, we developed a topical opioid paradigm in which the tail was immersed dimethyl sulfoxide (DMSO) solution containing various drugs. Alone, DMSO inactive tail-flick assay mice. solutions and peptides such as [D-Ala2,MePhe4, Gly(ol)5]enkephalin (DAMGO) produced potent, dose-dependent analgesia with radiant heat assay. The actions of drugs were local. Analgesia observed only regions...

Topical drugs avoid many of the problematic side effects systemic agents. Immersion tail a mouse into solution dimethyl sulfoxide (DMSO)-containing morphine produces dose-dependent, naloxone-sensitive, analgesia (ED(50) 6.1 mM; CL 4.3, 8.4) limited to portion exposed drug. DMSO alone in this paradigm had no analgesic activity. Like morphine, opioids levorphanol 5.0 3.8, 7.8) and buprenorphine 1. 1 0.7, 1.5) were effective topical analgesics. Lidocaine also was active tail-flick assay 2.5...

In contrast to the rapid development of tolerance morphine in CD-1 mice, is not seen 129/SvEv mice implanted with pellets or given daily injections for 5 days. Similarly, progressive and complete loss analgesia repeated dosing delta ligand [D-Pen2, D-Pen5]enkephalin observed mice. contrast, develops normally both kappa1 drug U50,488H kappa3 agent naloxone benzoylhdrazone. N-methyl-D-aspartate (NMDA) alone attenuates accelerates when morphine. NMDA has no significant effect either paradigm....

NPC17742 is a potent competitive NMDA antagonist. Low doses of prevent the development tolerance to repeated daily injections mu agonist morphine and kappa1 U50,488H. However, at these same without effect against kappa3 analgesic naloxone benzoylhydrazone (NalBzoH). At doses, does not significantly influence morphine's ED50 value following single or The ability block U50488H distinguishes this compound from other antagonists raises possibility subclasses antagonists. Furthermore, results...

In Brief The practice of combining opioids with nonsteroidal antiinflammatory drugs is widespread in the clinical management acute and chronic pain. Using mouse radiant heat tail-flick nociception model, we observed potent analgesia hydrocodone. contrast, ibuprofen as a single drug was inactive this model moderate to severe pain, perhaps reflecting its limited analgesic potential. Despite inactivity alone inclusion hydrocodone markedly enhanced response. Dose-response studies revealed an 50%...

Under chronic conditions of neuropathic pain, nociceptive C terminals are lost from their target region in spinal lamina II, leading to reduced thermal hyperalgesia. This the cord expresses high levels polysialic acid (PSA), a cell surface carbohydrate known weaken cell–cell interactions and promote plasticity. Experimental removal PSA exacerbates hyperalgesia results retention terminals, whereas it has no effect on plasticity touch Aβ fibers allodynia. We propose that expression at this...