Changes in thalamic nociception resulting from morphine- and meperidine-dependence in rats

Abstract

Rats were injected with progressively increasing doses of morphine or meperidine during a period of 3 to 40 days. From this colony of animals individual rats were used at 3- to 4-day intervals for electrophysiologic experiments to analyze the activity of nociceptive neurons in the somesthetic thalamus. After an i.p. injection of chloralose-urethane and the appropriate preparation for a stereotaxic microelectrode penetration of the thalamus, a nociceptive neuron was identified in the nucleus ventralis posterolateralis by its unique spacing of spike potentials emitted in response to pricking the foot with a pin. In addition to the short-latency response that formed a high activity peak on poststimulus time histograms, spikes following the stimulus up to 500 ms also formed activity peaks. Single-pulse stimulation of the sciatic nerve evoked the same response as pinpricks, but innocuous stimuli (pin shielded with a piece of cork) evoked a response without the late activity peaks. Only neurons that exhibited this differential response were regarded as nociceptive. Their response and spontaneous activity were accumulated separately on a digital computer. Following this, naloxone was infused i.v. and the computer accumulations were repeated. It was found that during naloxone-precipitated narcotic withdrawal, innocuous stimuli evoked responses indicative of pain; the nociceptive system was sensitized. Furthermore, a small dose of morphine or meperidine heightened the sensitization. This action of the narcotic agents was reversed by 5-hydroxytryptophan, which assisted the narcotics in suppressing pain in morphine- or meperidine-dependent rats but had no demonstrable effect in control animals. The spontaneous tonic activity of the nociceptive neurons of the somesthetic thalamus was high in rats exhibiting narcotic dependence. Naloxone decreased the count, but not to the value of the control animals. The sensitization of nociception can be explained by a decreased action of a neural pathway that descends from the periaqueductal gray matter via the nucleus raphe magnus to the spinal cord and there blocks the excitation of the spinothalamic tract cells by A-delta and C fibers. The mechanisms that increase the spontaneous activity of the thalamic nociceptive neurons remain unclear.