heroin and Acute-Pain

One objective of the National Institutes of Health Helping to End Addiction Long-term (HEAL) initiative is to accelerate research on safer and more effective medications for both pain and opioid use disorder. Ligands that activate the nociceptin opioid peptide receptor (NOP) constitute one class of candidate drugs for both applications. The present preclinical study determined the effectiveness of the NOP agonist Ro 64-6198 to produce antinociception in a pain-depressed behavior procedure and attenuate opioid self-administration in a heroin-vs-food choice procedure.. In Experiment 1, Adult Sprague-Dawley rats were equipped with microelectrodes and trained to respond for electrical brain stimulation in an intracranial self-stimulation (ICSS) procedure. The potency, time course, and receptor mechanism of effects produced by R0 64-6198 alone (0.32-3.2 mg/kg) on ICSS were examined, followed by evaluation of 0.32-1.0 mg/kg Ro 64-6198 effectiveness to block lactic acid-induced depression of ICSS. In Experiment 2, rats self-administered heroin under a heroin-vs-food choice procedure during a regimen of repeated, daily intraperitoneal administration of vehicle or Ro 64-6198 (1-3.2 mg/kg/day).. Ro 64-6198 produced dose- and time-dependent ICSS depression that was blocked by the selective NOP antagonist SB612111 but not by naltrexone. Ro 64-6198 failed to block acid-induced depression of ICSS. Repeated Ro 64-6198 pretreatment also failed to attenuate heroin-vs-food choice up to doses that significantly decreased operant behavior.. These results do not support the utility of Ro 64-6198 as a stand-alone medication for either acute pain or opioid use disorder.

Topics: Acute Pain; Animals; Dose-Response Relationship, Drug; Heroin; Imidazoles; Nociceptin; Opioid Peptides; Opioid-Related Disorders; Rats; Rats, Sprague-Dawley; Spiro Compounds

To establish the safety of an intranasal diamorphine (IND) spray in children.. An open-label, single-dose pharmacovigilance trial.. Emergency departments in eight UK hospitals.. Children aged 2-16 years with a fracture or other trauma.. Adverse events (AE) specifically related to nasal irritation, respiratory and central nervous system depression.. 226 patients received 0.1 mg/kg IND. No serious or severe AEs occurred. The incidence of treatment-emergent AEs (TEAEs) was 26.5% (95% CI 20.9% to 32.8%), 93% being mild. 89% were related to treatment, all being known effects of the drug or route of administration except for three events in two patients. 20.4% (95% CI 15.3% to 26.2%) patients reported nasal irritation, all mild except one moderate and one 'unknown' severity. No respiratory depression was reported. Three AEs related to reduced Glasgow Coma Score (GCS) occurred, all mild.. There were no safety concerns raised during the conduct of the study. In addition to expected side effects, IND can cause mild nasal irritation in a proportion of patients.. 2009-014982-16.

Topics: Acute Pain; Administration, Intranasal; Adolescent; Analgesics, Opioid; Child; Child, Preschool; Emergency Service, Hospital; England; Female; Heroin; Humans; Infant; Male; Pharmacovigilance

Acute leg ischemia after intra-arterial drug injection represents a critical vascular emergency scenario. Due to lack of evidence-based standards therapeutic strategies are oriented to the underlying pathomechanisms. For a sufficient therapy a close clinical monitoring and laboratory analyses as well as treatment with analgesics, anticoagulants, anti-inflammatory and spasmolytic agents are of utmost importance. This article reports on the diagnostic and therapeutic approaches in a 32-year-old patient with acute leg ischemia after intra-arterial administration of heroin and secondary infection with Peptostreptococcus and Peptoniphilus species.

Topics: Acute Pain; Adult; Gram-Positive Bacterial Infections; Heroin; Humans; Injections, Intra-Arterial; Ischemia; Leg; Peptostreptococcus