dynorphins and Psychomotor-Agitation

Law enforcement personnel often confront violent and dangerous individuals suffering from Excited Delirium Syndrome (ExDS) who need emergent medical evaluation and treatment to optimize the best outcomes for this potentially lethal medical emergency. These subjects typically require physical restraint and use of force measures to control them. We sought to determine if stress-related biomarkers can differentiate ExDS subjects when compared with agitation and stress under other circumstances, including agitation and extreme physical exhaustion and restraint coupled with emotional stressors.. This was a prospective multi-center study enrolling a convenience sample of patients who presented with agitation or ExDS. Patients were enrolled from three academic emergency departments (ED), two in the United States and one in Canada. Three study groups (SG) included: SG1) patients brought to the ED with ExDS based on the use of standardized clinical criteria; SG2) ED patients with acute agitation who were not in a clinical state of ExDS but required sedation; SG3) a laboratory control group of subjects exercised to physical exhaustion, restrained, and psychologically stressed with threat of Conducted Energy Device (CED) activation. We examined a panel of stress-related biomarkers, including norepinephrine (NE), cortisol, copeptin, orexin A, and dynorphin (Dyn) from the blood of enrolled subjects.. A total of 82 subjects were enrolled: 31 in the agitation group, 21 in the ExDS group, and 30 in the laboratory control group. Data were analyzed, comparing the findings between ExDS and the two other groups to determine if specific stress-related biomarkers are associated with ExDS. Biomarker comparisons between subjects identified with ExDS, agitation, and control groups demonstrated that cortisol levels were more elevated in the ExDS group compared with the other groups. Orexin was only significant in ExDs (with Agitated tendency but lot of variability in the group). NE and Dyn increased as response to stress in Agitated and ExDS.. Cortisol levels were more elevated in subjects in the ExDS group compared with the other comparison groups and orexin was elevated in ExDS compared to controls, a trend that did not reach statistical significance in the agitated group. The clinical or diagnostic significance of these difference have yet to be defined and warrants further study.

Topics: Adult; Biomarkers; Case-Control Studies; Death, Sudden; Delirium; Dynorphins; Emergency Service, Hospital; Glycopeptides; Humans; Hydrocortisone; Norepinephrine; Orexins; Police; Prisoners; Prospective Studies; Psychomotor Agitation; Restraint, Physical; Sampling Studies; Stress, Physiological

Morphine-3-glucuronide (M3G) administered centrally produces dose-dependent neuro-excitatory behaviours in rodents via a predominantly non-opioid mechanism. The endogenous opioid peptide, dynorphin A (Dyn A) (1-17), is rapidly cleaved in vivo to the relatively more stable fragment Dyn A(2-17) which also produces excitatory behaviours in rodents via a non-opioid mechanism. This study investigated the possible contribution of Dyn A(2-17) to the neuro-excitatory behaviours evoked by supraspinally and spinally administered M3G in male Sprague-Dawley (SD) rats. Marked qualitative differences in behaviours were apparent following administration of M3G and Dyn A(2-17). Administration of 11 nmol i.c.v. doses of M3G produced intermittent myoclonic jerks, tonic-clonic convulsions, and ataxia, as well as postural changes, whereas i.c.v. Dyn A(2-17) at 15 nmol produced effects on body posture alone. Administration of 11 nmol i.t. doses of M3G produced intermittent explosive motor activity, and touch-evoked agitation, as well as postural changes, whereas i.t. Dyn A(2-17) at 15 nmol produced postural changes, touch-evoked agitation, and paralysis. Pre-treatment with Dyn A antiserum (200 microg) markedly attenuated total behavioural excitation following i.c.v. and i.t. administration of Dyn A(2-17) by approximately 94% and 78%, respectively. However, total behavioural excitation following i.c.v. and i.t. administration of M3G was less markedly attenuated (both approximately 27%) by pre-treatment with Dyn A antiserum, with reductions in tonic-clonic convulsions ( approximately 43%), explosive motor behaviour ( approximately 28%), and touch-evoked agitation ( approximately 22%). The present findings discount a major role for Dyn A in mediating the neuro-excitatory effects of M3G, although it may contribute to maintaining some individual neuro-excitatory behaviours.

Topics: Animals; Area Under Curve; Central Nervous System Stimulants; Dynorphins; Injections, Intraventricular; Injections, Spinal; Male; Morphine Derivatives; Motor Activity; Paralysis; Peptide Fragments; Posture; Psychomotor Agitation; Rats; Rats, Sprague-Dawley