Differential Inhibition of Bilateral Phrenic Bursting following Pulmonary Chemoreflex in Rats with Chronic Cervical Spinal Hemisection

Abstract

High cervical spinal injury usually interrupts bulbospinal pathways and results in inactivation of phrenic bursting ipsilateral to the lesion. The ipsilateral phrenic activity can partially recover over weeks to months post‐injury due to activation of the latent crossed phrenic pathway. Ipsilateral phrenic nerve exhibits a greater capacity to increase activity during respiratory challenges than the contralateral phrenic nerve. However, whether bilateral phrenic nerves show a differential response to respiratory inhibitory inputs is unclear. Accordingly, present study was designed to examine bilateral phrenic bursting in response to capsaicin‐induced pulmonary chemoreflex, a robust respiratory inhibitory stimulus. Bilateral phrenic nerve activity were recorded in anesthetized and mechanically‐ventilated adult rats at 8‐9 weeks post‐C2 hemisection (C2Hx) or C2 laminectomy. Intra‐jugular capsaicin (1.5 µg/kg) injection was used to activate pulmonary C‐fibers to evoke the pulmonary chemoreflex. Present results showed capsaicin‐induced prolongation of expiratory duration (i.e., apnea) was significantly attenuated in C2Hx animals. However, ipsilateral phrenic activity was robustly inhibited after capsaicin treatment compared to contralateral phrenic nerve of C2Hx animals or ipsilateral phrenic nerve of uninjured animals. In addition, discharge onset of ipsilateral phrenic bursting of C2Hx animals is significantly delayed after capsaicin delivery. These results suggest that phrenic motor output is more susceptible to inhibitory inputs after cervical hemisection. Moreover, central (i.e., apnea) and spinal (i.e., inhibition of phrenic bursting) component of the pulmonary chemoreflex were differentially modulated during chronic injury phase.