Blockade of a motor response by cholinergic stimulation of the toad midbrain tegmentum.

Application of an acid solution to the dorsal skin of conscious toads having intact nervous system induces a scratching reflex and escape movements, as well as autonomic alterations (hypertension and tachycardia) that are part of the defense response. The motor components of this response are abolished or reduced by microinjection of 60, 30, 15 or 7.5 ng carbachol into the midbrain tegmentum. The cardiovascular components, however, continue to be present, although their amplitude is reduced. The depression of the motor response is statistically significant up to 15 minutes for the 60 ng dose, up to 10 minutes for the 15 and 30 ng doses, and only up to 5 minutes for the 7.5 ng dose. The data suggest that the midbrain tegmentum may modulate the reflex motor response triggered by a noxious stimulus and also participate in the organization of the escape movements. The importance of cholinergic agents in this modulation is discussed. The persistence of the cardiovascular component of the response shows the importance of this parameter as an indicator of alert situations.

Dental pain and injection of agents into the trigeminal nucleus of guinea pigs.

The effects of microinjections of carbachol (Carb), serotonin (5-HT) and noradrenaline (NOR) into the spinal trigeminal nucleus (STN) of guinea pigs were studied in superficially anesthetized animals (nembutal, 40 mg/kg) submitted to noxious dental stimulation (electric shock). The defense motor response (DMR) was studied during noxious stimulation through the control period and up to 60 minutes after chemical stimulation. The agents were microinjected into four sites in the bulbar-spinal projection of the STN. Carb (1 microgram/microliter) caused significantly decreased DMR when injected into all regions studied, with total DMR abolition into the site located 1.0 mm caudal to the obex. 5-HT (30 micrograms/microliters) and NOR (30 micrograms/microliters) elicited a less intense effect than Carb, causing significant reduction in DMR only when injected into two sites. These results suggest cholinergic, serotonergic and adrenergic involvement of the mechanism of aversive response to dental pain.

Pain reaction after topical NA and lesions of the obex region in the alert guinea pig.

A study was carried out on the effect of topical application of 3.0 micrograms/microliters noradrenalin (NA) to the obex of awake guinea pigs bearing electrolyte lesions and submitted to noxious peripheral stimulation (electric pulses). The animals with extensive lesions covering the area postrema (AP) and the solitary tract nucleus (STN) showed a marked increase in vocalization (V) and defense motor response (M) to the noxious peripheral stimulus after NA application. In the group bearing lesions restricted to the AP, the analgesic effect of NA was potentiated, with a marked decrease in V and M after noxious peripheral stimulation. These results suggest that the integrity of the STN is a fundamental requirement for the analgesic effect of NA topically applied to the obex, and that the AP may have an inhibitory tonic action on the STN in the modulation of the noxious reaction.

Integrated excitatory response to microinjections of L-glutamic acid into the reticular system of the toad.

Microinjections of L-glutamic acid into the mesencephalic tegmentum and diencephalon of anesthetized toads evoked an excitatory response consisting of electrocephalographic and electromyographic activation, and a rise in arterial blood pressure. Electromyographic responses were reduced or absent in diencephalically injected toads. Except for this case, all other components of the response always appeared together and presented the same time course. L-glutamic acid was able to activate a group of neurons at different levels of the reticular system involved in an integrated response of ergotropic nature.

Pain modulation in the adrenergically stimulated area postrema in the alert guinea pig.

The effect of chemical stimulation of the area postrema (AP) with noradrenalin (NOR) and its blocking agents was studied in alert guinea pigs submitted to noxious peripheral stimuli (electric shock). The animal's motor defense and vocalizing responses during and after nociceptive stimulation were studied. Topical administration of NOR in the AP at a concentration of 150 microgram/microliter decreased the vocalizing and movement responses with both threshold and overthreshold stimulation. Phentolamine (5 microgram/microliter) elicited the opposite response, i.e. increase in vocalization and movements. Propranolol elicited a brief reduction of the threshold response. These results suggest an involvement of the AP in the mechanism of nociceptive stimulation through alpha-adrenergic mediation. The inhibition of the response to the noxious stimulus may be the consequence of a vagal activation triggered by the AP.

Peripheral modulation of pain in conscious guinea pigs: effect of morphine, nalorphine and clonidine.

1. Morphine and nalorphine were shown to have a peripheral analgesic effect on conscious guinea pigs, producing a decrease in the vocalization response to noxious electrical stimulation. Naloxone antagonized the effect of morphine and nalorphine. 2. Locally administered clonidine had a peripheral analgesic effect on conscious guinea pigs, producing a decrease in the vocalization response to noxious electrical stimulation. 3. The peripheral analgesia of clonidine was antagonized by yohimbine and naloxone. The analgesic effect of clonidine was 250-300 times more potent than that of lidocaine. 4. It is suggested that alpha 2-adrenergic receptor agonists may activate enkephalin-like substances released at the peripheral level.

Mechanism of peripheral pain in the conscious guinea pig: effect of propranolol.

Noxious electric stimulation may release sympathetic mediators, since subcutaneously administered propranolol inhibited a peripheral analgesic effect by decreasing the vocalizing response of conscious guinea pigs to electric stimulation. Local injection of noradrenaline and isoprenaline induced increased vocalization to stimulation. Propranolol inhibited the effect of noradrenaline. The activation of beta-adrenergic receptors may participate in peripheral nociceptive information.

Inhibition of the response to pain by the action of serotonin and carbachol topically applied to the area postrema of conscious guinea pigs.

The amplitude of vocalization and the motor defense response evoked by painful electrical stimulation were recorded in unanesthetized guinea pigs submitted to topical application of 1.0 microgram/microliter carbachol to the area postrema. Carbachol was found to have an analgesic effect. A similar application of 3.0 micrograms/microliter 5-hydroxytryptamine (5-HT) also had an analgesic effect, whose duration, however, was only half that of carbachol and whose intensity was lower, although the latency of the response was 2 seconds for both drugs. When 100 micrograms/microliter lysergic acid was applied to the area postrema the results did not differ significantly from control values, with only a small tendency toward hyperalgesia being observed. The present results, taken together with those obtained with noradrenalin in a previous study, suggest that the rich endowment of neurotransmitters in the area postrema may indicate a polyvalent analgesic mechanism able to provide a finer regulation of analgesia.

Dental pain and sleep. Experimental study on guinea pigs (Cavia porcellus).

The relationship between pain and sleep was studied by using electrocorticograms (ECoG) taken from guinea pigs submitted to noxious stimulation (NS) of the dental pulp of the upper incisors, after local application of serotonin (5-HT) to the obex (a brain region inductive to sleep). The results showed that the dental electrical stimulation of the sleepy animal was capable of keeping this animal in a state of vigilance and excitation, suggesting that the trigeminal system probably acts on the sleep regulating centers.

Electroencephalographic serotonin synchronization: area postrema and solitary tract nucleus.

Unilateral microinjection of serotonin (5-HT) into the solitary tract nucleus (STN) increased the amplitude of all electroencephalographic (EEG) waves ipsilateral to the site of injection. Unilateral STN blockage by lidocaine blocked the ipsilateral effect of 5-HT. Unilateral lesion of the area postrema (AP) increased the amplitude of the ipsilateral EEG in response to 5-HT stimulation of the obex. In contrast, unilateral lesion of both AP and STN decreased the amplitude of the ipsilateral EEG response to 5-HT. The data show that the STN is critically involved in 5-HT synchronizing mechanism and that the AP may have an inhibitory tonic effect on the STN.