Naloxone-reversible analgesia induced by electrical stimulation of the habenula in the rat.

During a previous study of the nucleus parafascicularis (Pf), cells were recorded in the lateral habenula (HbL) which exhibited response patterns to peripheral noxious stimuli similar to those recorded in the Pf. In order to study the possible role of the habenular complex (Hb) in pain processing, we investigated the effect of electrical stimulation of the Hb on the tail-flick latency. For each series of experiments, the Hb of 15 female rats was implanted unilaterally, with bipolar electrodes, on either the right or left side. A week later, the animals were submitted to measurements of tail-flick latency, every 10 min, for a period of 3 h. The amount of analgesia was estimated by the percentage increase in latency. Five intensities of current (50, 100, 200, 300 and 400 microA) were used for stimulation during 60 s, at 50 Hz and 0.5-ms pulse width. A group of animals were given naloxone i.p. (1 mg/kg) 40 min after Hb stimulation at 200 microA to study the reversibility of the analgesia. A second group had their Hb destroyed by coagulation and the effect on tail-flick latency was checked once a week for 4 weeks. The results of these experiments clearly demonstrate Hb stimulation-induced analgesia, the maximum of which occurs 60-80 min after stimulation and then decreases slowly. The maximal amount of analgesia increases with the intensity of current up to 200 microA, without any behavioral side effects. At 300 microA, the analgesia is not significantly different from the one induced at 200 microA. However at 400 microA, behavioral side effects (fear, escape) appear and the analgesia is weaker. Two-hundred microA appears to be the most efficient current intensity and induces an average of 80% increase in tail-flick latency. The group which was given naloxone exhibited a dramatic and complete reversal of analgesia. The group which had their Hb destroyed did not show any difference from the control group a week after surgery. During the following weeks, both lesioned animals and controls exhibited a habituation-like analgesia, without any significant difference (the index of analgesia was 45.73 +/- 23.65% for the lesioned rats and 51.82 +/- 29.18% for the controls), which was not naloxone reversible. A review of the literature does not provide an explantation for Hb-induced analgesia.(ABSTRACT TRUNCATED AT 400 WORDS)