Single neurone studies of opioid tolerance and dependence at the ventrobasal thalamic level in an experimental model of clinical pain, the arthritic rat.
The aim of this electrophysiological study was to investigate the effects of an acute injection of morphine (1 mg/kg i.v.) or the opioid antagonist naloxone (0.6-2 mg/kg i.v.) on thalamic ventrobasal (VB) neuronal activities recorded in arthritic rats rendered tolerant/dependent by pretreatment with relatively low doses of morphine. Recordings were performed in animals immobilized by i.v. injections of gallamine triethiodide (Flaxedil) and artificially ventilated under a moderate gaseous anesthesia (mixture of one-third O2, two-thirds N2O, 0.5-0.6% halothane). This level of anesthesia, as checked by the electrocorticogram, was stable and appeared sufficiently deep, since no sign of suffering or stress could be detected. The efficacy of morphine on VB neuronal responses induced by mild stimulation of the joints was greatly reduced in morphine-pretreated arthritic rats, compared to naive animals (mean neuronal inhibition of 35 vs 85%, respectively). This indicates that the tolerance phenomena observed in behavioral studies are reflected at the VB level, on neurons involved in pain processes. In addition, naloxone (0.6, 1 and 2 mg/kg i.v.) induced a dramatic increase in the evoked (52, 88 and 93%) and spontaneous (64, 211 and 292%) VB neuronal activities recorded in morphine-pretreated arthritic rats, while these activities were not significantly altered in naive arthritic rats. The time-courses of the modifications induced by naloxone in morphine-pretreated arthritic animals were similar to those of the naloxone-precipitated morphine withdrawal observed in freely moving rats. These findings may represent the neuronal correlate at the VB level of the withdrawal response and/or the hyperalgesia induced in tolerant arthritic rats by high doses of naloxone.
Unité des Recherches de Physiopharmacologie du Système Nerveux, U 161 INSERM, Paris, France.
V
V
Kayser
N
N
Attal
Y L
YL
Chen
G
G
Guilbaud
D000818:Animals; D001169:Arthritis, Experimental / Q000503:physiopathology*; D004361:Drug Tolerance / Q000502:physiology; D005071:Evoked Potentials / Q000187:drug effects; D007596:Joints / Q000503:physiopathology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000503:physiopathology*; D009270:Naloxone / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D013788:Thalamus / Q000187:drug effects / Q000503:physiopathology*
D009270:Naloxone; D009020:Morphine