Eiko Tadaki

Respiratory depression caused by either morphine microinjection or repetitive electrical stimulation in the region of the nucleus parabrachialis of cats

In chloralose-urethane anesthetized, vagotomized, paralyzed and artificially ventilated cats, respiratory response to either repetitive electrical stimulation or micro-injection of morphine in the rostral pons was studied by recording the phrenic nerve discharges. In the region of the nucleus parabrachialis (PBN) and its ventral reticular formation, electrical stimulation delivered in 20 successive expiratory periods caused the respiratory depression to last long after the termination of stimulation. This respiratory-depressant effect could be reversed by naloxone. By a single electrical stimulation delivered in most of these effective sites, a phasic phrenic excitation was consistently elicited in the period of both expiration and inspiration, and the reduction in expiratory duration could be observed when the stimulation was delivered in expiratory period. In the microinjection study of 2.66 nmol morphine in 0.1 μl in the localized area of the dorsolateral portion of the PBN, a significant reduction in both respiratory outputs and the rate of increase in inspiratory activity could be induced within 1 min after the application. The respiratory depression thus caused by both methods was quite similar in several respiratory variables. Thus an involvement of the PBN region in long-lasting respiratory modulation mediated by endogenous opioid system is suggested.

Post-stimulus facilitatory and inhibitory effects on respiration induced by chemical and electrical stimulation of thin-fiber muscular afferents in dogs

In anesthetized, vagotomized, paralyzed, and artificially ventilated dogs, respiratory responses to both electrical stimulation of the muscle nerve and chemical stimulation of muscular (polymodal) receptors by means of intra-arterial injection of NaCl solution were studied by recording phrenic nervous discharges. During the period of stimulation both types of stimulation caused intensity-dependent facilitation of neural respiratory outputs. After cessation of stimulation, facilitation persisted for a long time (more than 5 min) with a lower intensity stimulation; however, suppression was observed with a higher intensity stimulation. The present results suggest that afferent inputs from the muscular polymodal receptors activate long-acting central mechanisms for enhancement or suppression of respiration.

Naloxone-reversible respiratory inhibition induced by muscular thin-fiber afferents in decerebrated cats

Stimulation of muscular thin-fiber afferents of cats causes two types of respiratory suppression: one is stimulus-locked suppression which is not affected by naloxone, and the other is naloxone-reversible respiratory suppression after cessation of the stimulation. Both types of respiratory suppression could still be evoked after decerebration of cats at the midcollicular level. The present experiment revealed that muscular thin-fiber afferents, presumably polymodal receptor afferents, caused respiratory inhibition mediated through an opiate system in the brain structure below the caudal part of the brain stem.

Respiratory changes induced by activation of testicular afferents in dogs

Reportedly, more than 90% of the testicular afferents of the dog are of the polymodal type. The possible involvement of these afferents in modulation of respiration was studied using anesthetized dogs, which had been vagotomized and with both common carotid arteries ligated. Electrical stimulation of the superior spermatic nerve at an intensity of 1/5 Tc (Tc: threshold intensity for C-fiber activation) induced no substantial changes in respiration, while above 1/2 Tc it induced an increase in minute expiratory volume (VE), or a decrease followed by an increase inVE. The pattern of respiratory change was converted from the former to the latter by increasing the stimulation frequency while maintaining the same intensity. Mechanical stimulation of the testis through a stimulator with a tip of 1 cm in diameter caused an increase ofVE at 200 g and a decrease followed by an increase ofVE above 500 g. Intraarterial injection of bradykinin (3×10−6 M), hypertonic saline (1.5 M) and high K+ solution (180 mM) to the spermatic artery induced similar respiratory changes. Pneumograms showed a shift in end-expiratory position even at stimulus intensities without significantVE changes. Phrenic nerve recordings from some artificially ventilated dogs, revealed an prolongation of the first expiratory phase followed by augmentation of phrenic activity, mostly an increase in respiratory rate. Comparison between afferent activities and reflex respiratory changes suggests that above described two types of respiratory changes are brought about by the activities of testicular polymodal receptors.

Possible Implication of N. Parabrachialis in Opioid-Mediated Respiratory Suppression Induced by Thin-Fiber Muscular Afferents

The great majority of thin-fiber muscular afferents are of the polymodal receptor type, signaling nociceptive information. Arterial injection of various algesic substances into the gastrocnemius muscle of anesthetized, spontaneously ventilated dogs, causes an increase in minute respiratory volume similar to increases observed in discharge rates of muscular polymodal receptors in response to the same stimulus.2 Such findings suggest an involvement of the muscular polymodal receptors in the respiratory response.