Opioid-resistant respiratory pathway from the preinspiratory neurones to abdominal muscles: in vivo and in vitro study in the newborn rat

• Published in: The Journal of physiology Vol. 545; no. 3; pp. 1017 - 1026
• Main Authors: Janczewski, Wiktor A., Onimaru, Hiroshi, Homma, Ikuo, Feldman, Jack L.
• Format: Journal Article
• Language: English
• Published: Oxford, UK The Physiological Society 15.12.2002; Blackwell Publishing Ltd; Blackwell Science Inc
• Subjects: Abdominal Muscles - drug effects; Abdominal Muscles - innervation; Abdominal Muscles - physiology; Animals; Animals, Newborn - physiology; Drug Resistance; Electromyography; Electrophysiology; Fentanyl - pharmacology; In Vitro Techniques; Inhalation - physiology; Lumbosacral Region; Medulla Oblongata - physiology; Narcotics - pharmacology; Neck; Neural Pathways - drug effects; Neural Pathways - physiology; Neurons - physiology; Original; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Opioid, mu - agonists; Respiratory System - innervation; Spinal Cord - physiology; Spinal Nerve Roots - drug effects; Spinal Nerve Roots - physiology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2002.023408

We report that after spontaneous breathing movements are stopped by administration of opioids (opioid-induced apnoea) in neonatal rats, abdominal muscles continue to contract at a rate similar to that observed during periods of ventilation. Correspondingly, in vitro bath application of a μ opioid receptor agonist suppresses the activity of the fourth cervical root (C4) supplying the diaphragm, but not the rhythmic activity of the first lumbar root (L1) innervating the abdominal muscles. This indicates the existence of opioid-resistant rhythmogenic neurones and a neuronal pathway transmitting their activity to the abdominal motoneurones. We have investigated this pathway by using a brainstem-spinal cord preparation of the neonatal rat. We identified bulbospinal neurones with a firing pattern identical to that of the L1 root. These neurones were located caudal to the obex in the vicinity of the nucleus retroambiguus. Resting potentials ranged from -49 to -40 mV (mean ± s.d. -44.0 ± 4.3 mV). The mean input resistance was 315.5 ± 54.8 MΩ. The mean antidromic latency from the L1 level was 42.8 ± 4.4 ms. Axons crossed the midline at the level of the cell body. The activity pattern of the bulbospinal neurones and the L1 root consisted of two bursts per respiratory cycle with a silent period during inspiration. This pattern is characteristic of preinspiratory neurones. We found that 11 % of the preinspiratory neurones projected to the area where the bulbospinal neurones were located. These preinspiratory neurones were found in the rostral ventrolateral medulla close (200-350 μm) to the ventral surface at the level of the rostral half of the nucleus retrofacialis. Our data suggest the operation of a disynaptic pathway from the preinspiratory neurones to the L1 motoneurones in the in vitro preparation. We propose that the same pathway is responsible for rhythmic activation of the abdominal muscles during opioid-induced apnoea in the newborn rat.