title: Brainstem injection of lidocaine releases the descending pain-inhibitory mechanisms in a rat model of mononeuropathy.
abstract: Lidocaine injections in the rostral ventromedial medulla (RVM) have been shown to produce significant reduction of neuropathic manifestations in rats. This effect has been attributed to selective block of a pain descending facilitatory system, responsible for chronic pain. However, recent observations from our laboratory did not provide confirmation to this hypothesis. We aimed, therefore, to investigate the spinal synaptic mechanisms activated by lidocaine injections in the RVM. Rats were subjected, under deep anesthesia, to the induction of mononeuropathy on one hindpaw, and to the stereotaxic implantation of chronic cannulae in the RVM for the injection of lidocaine or GABA antagonists. Implanted intrathecal catheter in the lumbosacral space was used for the injection of specific antagonists to GABA, 5HT, glycine, noreadrenaline and dopamine, prior to lidocaine. Tactile and cold hyperreactivity and heat hyperalgesia were assessed using von Frey hair filaments, acetone drop test and heat-induced paw withdrawal, respectively. Lidocaine injections produced significant inhibition of all neuropathic manifestations. Intrathecal injection of antagonists to GABA (bicucullin, picrotoxin and saclofen), serotonin 5HT(1-2) (ketanserin and methysergide) and α- (phentoalmine, yohimbine) and β- (propranolol) adrenergic receptors, suppressed the lidocaine inhibitory effects; while partial or no attenuation were observed following pretreatment with glycine and dopamine D(2/3) antagonists. Comparable effects were observed with RVM injection of GABA antagonists. Lidocaine injection in the RVM results in a release of the descending pain-inhibitory systems from a tonic gabaergic inhibition. This descending system involves the activation of gabaergic, serotonergic and adrenergic mechanisms at the level of the spinal dorsal horn.
authors: Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon. nesaade@aub.edu.lb
authors: Nayef E
authors: NE
authors: Saadé
authors: Hassen A
authors: HA
authors: Al Amin
authors: Jad
authors: J
authors: Barchini
authors: Sima
authors: S
authors: Tchachaghian
authors: Farah
authors: F
authors: Shamaa
authors: Suhayl J
authors: SJ
authors: Jabbur
authors: Samir F
authors: SF
authors: Atweh
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000187:drug effects* / Q000502:physiology*; D003080:Cold Temperature; D004195:Disease Models, Animal; D005260:Female; D006358:Hot Temperature; D007278:Injections, Spinal; D008012:Lidocaine / Q000008:administration & dosage*; D008845:Microinjections; D020422:Mononeuropathies / Q000188:drug therapy* / Q000209:etiology*; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008012:Lidocaine