Cholinergic Modulation of Narcoleptic Attacks in Double Orexin Receptor Knockout Mice

To investigate how cholinergic systems regulate aspects of the sleep disorder narcolepsy, we video-monitored mice lacking both orexin (hypocretin) receptors (double knockout; DKO mice) while pharmacologically altering cholinergic transmission. Spontaneous behavioral arrests in DKO mice were highly similar to those reported in orexin-deficient mice and were never observed in wild-type (WT) mice. A survival analysis revealed that arrest lifetimes were exponentially distributed indicating that random, Markovian processes determine arrest lifetime. Low doses (0.01, 0.03 mg/kg, IP), but not a high dose (0.08 mg/kg, IP) of the cholinesterase inhibitor physostigmine increased the number of arrests but did not alter arrest lifetimes. The muscarinic antagonist atropine (0.5 mg/kg, IP) decreased the number of arrests, also without altering arrest lifetimes. To determine if muscarinic transmission in pontine areas linked to REM sleep control also influences behavioral arrests, we microinjected neostigmine (50 nl, 62.5 µM) or neostigmine + atropine (62.5 µM and 111 µM respectively) into the nucleus pontis oralis and caudalis. Neostigmine increased the number of arrests in DKO mice without altering arrest lifetimes but did not provoke arrests in WT mice. Co-injection of atropine abolished this effect. Collectively, our findings establish that behavioral arrests in DKO mice are similar to those in orexin deficient mice and that arrests have exponentially distributed lifetimes. We also show, for the first time in a rodent narcolepsy model, that cholinergic systems can regulate arrest dynamics. Since perturbations of muscarinic transmission altered arrest frequency but not lifetime, our findings suggest cholinergic systems influence arrest initiation without influencing circuits that determine arrest duration

Peribulbar versus retrobulbar anaesthesia for cataract surgery.

BACKGROUND: Cataract is a major cause of blindness worldwide. Unless medically contraindicated, cataract surgery is usually performed under local (regional) anaesthesia. Local anaesthesia involves the blockage of a nerve subserving a given part of the body by infiltration of the area around the nerve with local anaesthetic. The two main approaches in the eye are retrobulbar and peribulbar. There is debate over whether the peribulbar approach provides more effective and safer anaesthesia for cataract surgery than retrobulbar block. OBJECTIVES: The objective of this review was to assess the effects of peribulbar anaesthesia (PB) compared to retrobulbar anaesthesia (RB) on pain scores, ocular akinesia, patient acceptability and ocular and systemic complications. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 4); MEDLINE (1960 to December 2007); and EMBASE (1980 to December 2007). SELECTION CRITERIA: We included randomized controlled clinical trials comparing peribulbar anaesthesia and retrobulbar anaesthesia for cataract surgery. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted trial authors for additional information, study methodology and missing data. We carried out a descriptive narrative of results as the methods used by the included stories for reporting the outcomes varied. We performed a subgroup analysis for globe akinesia. MAIN RESULTS: We included six trials involving 1438 participants. Two of the six trials had a low risk of bias; the remaining four had a moderate risk of bias. There was no evidence of any difference in pain perception during surgery with either retrobulbar or peribulbar anaesthesia. Both were largely effective. There was no evidence of any difference in complete akinesia or the need for further injections of local anaesthetic. Conjunctival chemosis was more common after peribulbar block (relative risk (RR) 2.11, 95% confidence Interval (CI) 1.46 to 3.05) and lid haematoma was more common after retrobulbar block (RR 0.36, 95% CI 0.15 to 0.88). Retrobulbar haemorrhage was uncommon and occurred only once, in a patient who had a retrobulbar block. AUTHORS' CONCLUSIONS: There is little to choose between peribulbar and retrobulbar block in terms of anaesthesia and akinesia during surgery in terms of acceptability to patients, need for additional injections and development of severe complications. Severe local or systemic complications were rare in PB and RB