The cloning of a fourth member of the opioid receptor family has led to the discovery of a new neuropeptide termed orphanin FQ or nociceptin (OFQ/N). Studies in CD-1 mice confirm the ability of OFQ/N to rapidly induce hyperalgesia within 15 min which is insensitive to opioid antagonists. This is followed in the next 30 min by loss of hyperalgesia and the appearance of analgesia in the tailflick...

The ability of neuropeptide Y to potently stimulate food intake is dependent in part upon the functioning of mu and kappa opioid receptors. The combined use of selective opioid antagonists directed against mu, delta or kappa receptors and antisense probes directed against specific exons of the MOR-1, DOR-1, KOR-1 and KOR-3/ORL-1 opioid receptor genes has been successful in characterizing the pr...

BACKGROUND Nor-BNI, GNTI and JDTic induce selective κ opioid antagonism that is delayed and extremely prolonged, but some other effects are of rapid onset and brief duration. The transient effects of these compounds differ, suggesting that some of them may be mediated by other targets. RESULTS In binding assays, the three antagonists showed no detectable affinity (K(i)≥10 µM) for most non-opi...

We tested the hypothesis that noxious stimuli induce pain modulation by activation of supraspinal structures. We found that intense noxious stimuli (i.e., subdermal injection of capsaicin or paw immersion in hot water) induced profound attenuation of the jaw-opening reflex in the anesthetized rat; forepaw subdermal capsaicin also elevated the mechanical hindpaw-withdrawal threshold in the awake...

AtT-20 cells, which make and release beta-endorphin, or AtT-20/hENK cells, an AtT-20 cell line transfected with the human proenkephalin gene and secreting enkephalin as well as presumably beta-endorphin, were implanted in mouse spinal subarachnoid space. Cell implants did not affect the basal response to thermal nociceptive stimuli. Administration of isoproterenol, believed to stimulate secreti...

Ultra-low-dose opioid antagonists, when combined with opiates, increase the analgesic efficacy and duration of analgesia of the opiate. This enhanced and prolonged analgesia was recently demonstrated in a 350-patient Phase II clinical trial of Oxytrex, a novel drug candidate that combines oxycodone with an ultra-low dose of the opioid antagonist naltrexone. Extensive preclinical data also show ...

Narcotic use in pregnancy has been a noticeable clinical development con­ fronting the nursing and medical staff at the Sioux Lookout Meno Ya Win Health Centre.3 This regional mater­ nity centre provides prenatal services and obstetric services to a catchment area of 28 000 primarily First Nations people.4 The services include 400 de­ liveries annually. Narcotic use during pregnancy became a cl...

Behavioral and autonomic signs of the morphine withdrawal syndrome were measured in dependent rats injected with the opiate antagonist naloxone. The purpose of this study was to determine whether spinal cholinergic pathways play a role in the expression of spinally mediated withdrawal symptoms. Intrathecal (i.t.) administration of 1 microgram carbachol or 5 micrograms neostigmine resulted in in...

We have previously demonstrated that central administration of interleukin (IL)-1beta suppresses natural killer (NK) cell activity, impairs NK-mediated lung clearance of tumor cells, and enhances tumor colonization. The central pathways activated by IL-1beta are as yet unknown. Using an in vivo model of tumor colonization, this study examined the role of central noradrenergic, opioid and prosta...