title: Brain penetration of local anaesthetics in the rat: Implications for experimental neuroscience.
abstract: Multiple experimental neuroscience techniques rely on the use of general anaesthesia to minimize the discomfort associated to animal restraint and to achieve a more effective control of relevant physiological parameters. In order to minimise potential interference on brain neuronal activity, such studies are typically conducted at low anaesthetic doses. This practice is often coupled to peripheral infiltration of local anaesthetics to provide supplementary analgesia and prevent sub-threshold activation of pain pathways that may confound central measurements of brain function. However, little is known of the effect of peripheral anaesthesia on central measurements of brain activity in small laboratory animal species. In order to begin to address this question, we measured total and free brain exposure of five different local anaesthetics following subcutaneous infiltration of analgesic doses in a surgical protocol widely used in rodent neuroimaging and electrophysiology studies. Notably, all the anaesthetics exhibited detectable total and free brain concentrations at all the time points examined. Lidocaine and mepivacaine showed the highest free brain exposures (>525 ng/g), followed by bupivacaine and ropivacaine (>70 ng/g). The ester-type local anaesthetic tetracaine produced the lowest free brain exposure (<8.6 ng/g). Our data suggest that peripheral administration of local anaesthetics in small laboratory animals could result in pharmacologically active brain exposures that might influence and confound central measurements of brain function. The use of the ester-type anaesthetic tetracaine produced considerably lower brain exposure, and may represent a viable experimental option when local anaesthesia is required.
authors.affiliation: Department of Laboratory Animal Science, GlaxoSmithKline Research Centre, Via Fleming 4, 37135 Verona, Italy. livia.m.ferrari@gsk.com
authors.forename: Livia
authors.initials: L
authors.lastname: Ferrari
authors.forename: Valerio
authors.initials: V
authors.lastname: Crestan
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Sabattini
authors.forename: Federica
authors.initials: F
authors.lastname: Vinco
authors.forename: Stefano
authors.initials: S
authors.lastname: Fontana
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gozzi
mesh_terms: D000577:Amides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D001774:Blood Chemical Analysis; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002045:Bupivacaine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D002404:Catheterization; D005263:Femoral Artery; D008012:Lidocaine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D013058:Mass Spectrometry; D008619:Mepivacaine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077212:Ropivacaine; D013748:Tetracaine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D014139:Tracheostomy
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D013748:Tetracaine; D000077212:Ropivacaine; D008012:Lidocaine; D008619:Mepivacaine; D002045:Bupivacaine