title: Repeated intrathecal administration of ropivacaine causes neurotoxicity in rats.
abstract: Previous studies have shown that ropivacaine is the least neurotoxic local anaesthetic. Most of the data derive from short-term ropivacaine injection into the subarachnoid space. Intrathecal administration  for a prolonged period, and the histological changes and behavioural effects of repeated intrathecal administration, have not previously been investigated. We studied the possible neurotoxicity of intrathecal injection of ropivacaine in a rat model. Rats received 0.12 ml/kg body weight of ropivacaine at concentrations of 0.5 or 1%, or normal saline only, via an implanted intrathecal catheter at 90-minute intervals for 12 hours. On days 1, 3, 5, 7, 14 and 28, the  spinal cord was examined by light and electron microscopy at the L3 level. We assessed sensory thresholds to noxious stimulation, behavioural change and protein kinase B immunoreactivity for possible neuronal injury within the spinal cord. Ropivacaine 1% induced thermal hyperalgesia and mechanical allodynia, neuronal injury characterised by tissue oedema, proliferation of glial cells, neuronal morphology changes and degeneration and protein kinase B expression. There were no significant differences in motor function as a result of different concentrations of ropivacaine.  Repeated intrathecal injection of ropivacaine 1% can induce neurotoxicity in rats. Our data suggests that expression of protein kinase B might be involved in this neurotoxicity.
authors.affiliation: Department of Anesthesiology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Z H
authors.initials: ZH
authors.lastname: Sun
authors.forename: X P
authors.initials: XP
authors.lastname: Xu
authors.forename: Z B
authors.initials: ZB
authors.lastname: Song
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.forename: N
authors.initials: N
authors.lastname: Wang
authors.forename: Q L
authors.initials: QL
authors.lastname: Guo
mesh_terms: D000577:Amides / Q000008:administration & dosage / Q000633:toxicity*; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D008297:Male; D020258:Neurotoxicity Syndromes / Q000209:etiology*; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077212:Ropivacaine
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine; D051057:Proto-Oncogene Proteins c-akt