Anaesthetic Impairment of Immune Function Is Mediated via GABAA Receptors

GABA(A) receptors are members of the Cys-loop family of neurotransmitter receptors, proteins which are responsible for fast synaptic transmission, and are the site of action of wide range of drugs. Recent work has shown that Cys-loop receptors are present on immune cells, but their physiological roles and the effects of drugs that modify their function in the innate immune system are currently unclear. We are interested in how and why anaesthetics increase infections in intensive care patients; a serious problem as more than 50% of patients with severe sepsis will die. As many anaesthetics act via GABA(A) receptors, the aim of this study was to determine if these receptors are present on immune cells, and could play a role in immunocompromising patients.We demonstrate, using RT-PCR, that monocytes express GABA(A) receptors constructed of α1, α4, β2, γ1 and/or δ subunits. Whole cell patch clamp electrophysiological studies show that GABA can activate these receptors, resulting in the opening of a chloride-selective channel; activation is inhibited by the GABA(A) receptor antagonists bicuculline and picrotoxin, but not enhanced by the positive modulator diazepam. The anaesthetic drugs propofol and thiopental, which can act via GABA(A) receptors, impaired monocyte function in classic immunological chemotaxis and phagocytosis assays, an effect reversed by bicuculline and picrotoxin.Our results show that functional GABA(A) receptors are present on monocytes with properties similar to CNS GABA(A) receptors. The functional data provide a possible explanation as to why chronic propofol and thiopental administration can increase the risk of infection in critically ill patients: their action on GABA(A) receptors inhibits normal monocyte behaviour. The data also suggest a potential solution: monocyte GABA(A) receptors are insensitive to diazepam, thus the use of benzodiazepines as an alternative anesthetising agent may be advantageous where infection is a life threatening problem

Overview of diagnosis and management of paediatric headache. Part I: diagnosis

Headache is the most common somatic complaint in children and adolescents. The evaluation should include detailed history of children and adolescents completed by detailed general and neurological examinations. Moreover, the possible role of psychological factors, life events and excessively stressful lifestyle in influencing recurrent headache need to be checked. The choice of laboratory tests rests on the differential diagnosis suggested by the history, the character and temporal pattern of the headache, and the physical and neurological examinations. Subjects who have any signs or symptoms of focal/progressive neurological disturbances should be investigated by neuroimaging techniques. The electroencephalogram and other neurophysiological examinations are of limited value in the routine evaluation of headaches. In a primary headache disorder, headache itself is the illness and headache is not attributed to any other disorder (e.g. migraine, tension-type headache, cluster headache and other trigeminal autonomic cephalgias). In secondary headache disorders, headache is the symptom of identifiable structural, metabolic or other abnormality. Red flags include the first or worst headache ever in the life, recent headache onset, increasing severity or frequency, occipital location, awakening from sleep because of headache, headache occurring exclusively in the morning associated with severe vomiting and headache associated with straining. Thus, the differential diagnosis between primary and secondary headaches rests mainly on clinical criteria. A thorough evaluation of headache in children and adolescents is necessary to make the correct diagnosis and initiate treatment, bearing in mind that children with headache are more likely to experience psychosocial adversity and to grow up with an excess of both headache and other physical and psychiatric symptoms and this creates an important healthcare problem for their future life

Effect of extradurally administered morphine on postoperative analgesia in dogs undergoing surgery for thoracolumbar intervertebral disk extrusion

Objective-To investigate the effect of intraoperative extradural morphine administration on postoperative analgesia in dogs undergoing thoracolumbar spinal surgery to treat disk extrusion. Design-Prospective clinical trial. Animals-26 client-owned dogs undergoing thoracolumbar spinal surgery. Procedures-Animals were randomly allocated to receive morphine (0.1 mg/kg [0.045 mg/lb], extradurally) or no treatment (control group). Following preanesthetic medication with methadone (0.25 mg/kg [0.11 mg/lb], IM), anesthesia was induced with propofol and maintained with isoflurane or sevoflurane in oxygen. Lidocaine and fentanyl were administered during surgery in both groups at fixed rates. In the morphine administration group, morphine was splashed over the dura mater immediately prior to wound closure. Postoperative analgesia was assessed for 48 hours by assessors unaware of group allocation, and methadone was administered as rescue analgesic. Demographic characteristics, urinary output, days of hospitalization, and perioperative use of analgesics were compared via a Mann-Whitney U test. Results-Demographic data were similar between groups. In the morphine administration group, 2 of 13 dogs required postoperative methadone, and in the control group, methadone was administered to 11 of 13 dogs. The total number of doses of methadone administered in the 48 hours after surgery was 28 in the control group and 3 in the morphine administration group. No adverse effects were recorded in any group. Conclusions and Clinical Relevance-Intraoperative extradural morphine administration was effective in reducing postoperative analgesic requirement. Dogs undergoing thoracolumbar spinal surgery benefited from topical administration of preservative-free morphine administered directly on the dura mater as part of analgesic management

Osmophobia in juvenile patiens suffering from migraine and tension-type headache

Rome 27-30 sept. The Journal of Headache and Pain, 2006, 7(4): p. 25

Osmophobia in juvenile primary headache.

This study was planned to investigate the prevalence of osmophobia in juvenile headache sufferers and to analyse the diagnostic utility of osmophobia in order to distinguish migraine without aura from episodic tension-type headache. We examined 305 consecutive patients presenting at our Paediatric Headache Centre. A semistructured questionnaire was given to 275 selected patients affected by migraine or tension-type headache. The prevalence of osmophobia during attacks was 18.5%, mainly in migraine patients (25.1%) vs. those with tension-type headache (8.3%). Osmophobia showed more specificity than phonophobia or photophobia in the differential diagnosis between migraine and tension-type headache. In conclusion, this study demonstrates that osmophobia resulted in a symptom with poor sensitivity (27.1%) but high specificity (92%) that could become a supportive diagnostic criterion even in children for the differential diagnosis between migraine without aura and tension-type headache

Osmophobia in juvenile primary headaches

J Headache and Pai