Phrenic motor outputs in response to bronchopulmonary C-fibre activation following chronic cervical spinal cord injury.
Activation of bronchopulmonary C-fibres, the main chemosensitive afferents in the lung, can induce pulmonary chemoreflexes to modulate respiratory activity. Following chronic cervical spinal cord injury, bronchopulmonary C-fibre activation-induced inhibition of phrenic activity was exaggerated. Supersensitivity of phrenic motor outputs to the inhibitory effect of bronchopulmonary C-fibre activation is due to a shift of phrenic motoneuron types and slow recovery of phrenic motoneuron discharge in cervical spinal cord-injured animals. These data suggest that activation of bronchopulmonary C-fibres may retard phrenic output recovery following cervical spinal cord injury. The alteration of phenotype and discharge pattern of phrenic motoneuron enables us to understand the impact of spinal cord injury on spinal respiratory activity.



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-1) 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.
Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan. kzlee@mail.nsysu.edu.tw.|Centre for Neuroscience, National Sun Yat-sen University, Kaohsiung, Taiwan. kzlee@mail.nsysu.edu.tw.|Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Taiwan. kzlee@mail.nsysu.edu.tw.|Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan. kzlee@mail.nsysu.edu.tw.|Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan. kzlee@mail.nsysu.edu.tw.
Kun-Ze
KZ
Lee
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D066193:Cervical Cord / Q000187:drug effects / Q000502:physiology*; D002574:Cervical Vertebrae / Q000187:drug effects / Q000502:physiology; D008168:Lung / Q000187:drug effects / Q000294:innervation* / Q000503:physiopathology; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*; D012119:Respiration / Q000187:drug effects; D013119:Spinal Cord Injuries / Q000503:physiopathology*
D002211:Capsaicin