Phrenic motor outputs in response to bronchopulmonary C‐fibre activation following chronic cervical spinal cord injury

Abstract

Cervical spinal injury interrupts bulbospinal pathways and results in cessation of phrenic bursting ipsilateral to the lesion. The ipsilateral phrenic activity can partially recover over weeks to months following injury due to the activation of latent crossed spinal pathways and exhibits a greater capacity to increase activity during respiratory challenges than the contralateral phrenic nerve. However, whether the bilateral phrenic nerves demonstrate differential responses to respiratory inhibitory inputs is unclear. Accordingly, the present study examined bilateral phrenic bursting in response to capsaicin-induced pulmonary chemoreflexes, a robust respiratory inhibitory stimulus. Bilateral phrenic nerve activity was recorded in anaesthetized and mechanically ventilated adult rats at 8-9 weeks after C2 hemisection (C2Hx) or C2 laminectomy. Intra-jugular capsaicin (1.5 μg kg ) injection was performed to activate the bronchopulmonary C-fibres to evoke pulmonary chemoreflexes. The present results indicate that capsaicin-induced prolongation of expiratory duration was significantly attenuated in C2Hx animals. However, ipsilateral phrenic activity was robustly reduced after capsaicin treatment compared to uninjured animals. Single phrenic fibre recording experiments demonstrated that C2Hx animals had a higher proportion of late-inspiratory phrenic motoneurons that were relatively sensitive to capsaicin treatment compared to early-inspiratory phrenic motoneurons. Moreover, late-inspiratory phrenic motoneurons in C2Hx animals had a weaker discharge frequency and slower recovery time than uninjured animals. These results suggest bilateral phrenic nerves differentially respond to bronchopulmonary C-fibre activation following unilateral cervical hemisection, and the severe inhibition of phrenic bursting is due to a shift in the discharge pattern of phrenic motoneurons.

Mild Acute Intermittent Hypoxia Improves Respiratory Function in Unanesthetized Rats With Midcervical Contusion

“…38 Moreover, prolongation of the expiratory duration during activation of pulmonary stretch receptors and bronchopulmonary C-fibers was also attenuated in cervical spinal injured rats. 9,39-41 These data imply that cervical SCI may restrict the alteration of respiratory frequency in response to respiratory stimuli. Interestingly, the respiratory frequency of contused animals, but not sham surgery animals, remained higher than baseline at 5 minutes after first hypoxic treatment, suggesting offset STP of respiratory frequency was evident in contused animals.…”

Impact of cervical spinal cord contusion on the breathing pattern across the sleep-wake cycle in the rat

“…First, the cervical spinal contusion directly damaged the bulbospinal respiratory pathways (27,28); thus there were fewer phrenic motoneurons still receiving projections from the premotor neuron in the brainstem when the respiratory drives were lower during sleep. Second, the excitability and phenotype of phrenic motoneurons were changed following cervical spinal cord injury (23,26,32), which may further interfere with the effect of sleep-induced changes in the respiratory drives on the phrenic motor output. Third, our recent report indicated that upper airway function was also impacted by cervical spinal cord injury (34).…”

“…For example, a rapid shallow breathing pattern was observed in rats with high-and midcervical spinal cord injuries (29). The phrenic electroneurogram and diaphragm electromyogram were significantly impacted by cervical spinal cord injury (18,23,28,55,58,59). These animal models were also used to evaluate the effectiveness of several potential therapeutic strategies for improving respiratory function, such as cellular transplantation, pharmacological administration, neurorehabilitative training, and magnetic/electrical stimulation (13,16,25,27,36,49,57).…”

5-HT7 Receptor Inhibition Transiently Improves Respiratory Function Following Daily Acute Intermittent Hypercapnic-Hypoxia in Rats With Chronic Midcervical Spinal Cord Contusion

“…In addition, alteration of phrenic motoneuronal excitability following cervical spinal cord injury may also potentiate the effect of dAIH and/or 5-HT7 receptor antagonist. [42][43][44] However, since our injury leads to a phrenic motoneuronal loss on the injured side, 10,11 we cannot rule out that the phrenic neuroplasticity that sustains the tidal volume increase in response to dAIH could happen into the phrenic motoneurons in the intact side, 45 as well as other respiratory-associated muscles such as the intercostals. 21,46,47 In addition, supraspinal respiratory-related nucleus and/or spinal interneurons may be also involved in modulating the tidal volume in our current experimental model.…”