Alteration of GABAergic and glycinergic mechanisms by lidocaine injection in the rostral ventromedial medulla of neuropathic rats.
Attenuation of neuropathic manifestations in experimental animals, by lidocaine injection in the rostral ventro-medial medulla (RVM), has been traditionally attributed to selective block of a descending pain facilitatory system. However, the presence of descending fibers carrying this effect and the selective action of lidocaine on the facilitatory neurons, have not been supported by convincing experimental evidence. The present study aimed to investigate the mechanisms underlying the hypoalgesic action of lidocaine injection in the brainstem. Several groups of rats were subjected to mononeuropathy on their left hind paws, according to the model of spared nerve injury, and were subsequently implanted with guide cannulae in the RVM. After recovery, rats received injections of lidocaine, GABA and glycine agonists or antagonists and their effects were assessed on behavioral tests of allodynia and hyperalgesia. Injections of lidocaine at doses ranging between 0.05% and 2% produced attenuation at high doses and no effects or increasing hyperalgesia at low doses. GABA and glycine agonists increased neuropathic manifestations while their antagonists elicited the opposite effects. A combined injection of GABA agonist or glycine with lidocaine (0.5%) prevented the inhibitory effects of lidocaine injection alone. Our results are in line with the abundant documentation on the alteration of the function of inhibitory neurons by lidocaine and reveal a possible action of the injected high doses on the GABAergic and glycinergic neurons in the RVM. The resulting block of the inhibitory tone exerted by these neurons can lead to a release of the descending pain inhibitory systems.
Department of Human Morphology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon Department of Physiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon Department of Psychiatry, Faculty of Medicine, American University of Beirut, Beirut, Lebanon Department of Internal Medicine, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Nayef E
NE
Saadé
Hassen
H
Al Amin
Sima
S
Tchachaghian
Suhayl J
SJ
Jabbur
Samir F
SF
Atweh
D000779:Anesthetics, Local / Q000008:administration & dosage; D000818:Animals; D005260:Female; D005998:Glycine / Q000378:metabolism*; D006930:Hyperalgesia / Q000378:metabolism* / Q000517:prevention & control*; D007267:Injections; D008012:Lidocaine / Q000008:administration & dosage*; D008526:Medulla Oblongata / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000779:Anesthetics, Local; D005680:gamma-Aminobutyric Acid; D008012:Lidocaine; D005998:Glycine