Diaphragm pacing elicits respiratory plasticity in awake rodents after C2 hemisection.

Cervical spinal cord injury (cSCI) creates profound respiratory deficits that are commonly managed with chronic mechanical ventilation. Diaphragm pacing (DP) is an emerging clinical intervention designed to combat the deleterious effects associated with chronic mechanical ventilation. While anecdotal evidence suggests that DP may restore independent breathing, the impact of daily DP on respiratory output is unknown. Therefore, we investigated if DP induces ventilatory and diaphragm electromyography (EMG) plasticity in awake rodents following cSCI. All animals (n = 42) were implanted with diaphragm EMGs, received a left incomplete C2 hemisection, and were treated with DP, DP + dorsal rhizotomy, or served as controls (no DP). In animals receiving a dorsal rhizotomy, the left cervical dorsal roots (C4-C6) were cut to test if phrenic afferents are necessary for the induction of plasticity. One week after C2 hemisection, we delivered daily DP for 1 h/day (5 min on/5 min off) and recorded ventilation and diaphragm EMG output for 60 min over 4 consecutive days. During DP, we found an increase in tidal volume. After DP, tidal volume remained elevated in males for at least 60 min, and to a lesser extent in females. DP increased diaphragm EMG amplitude 60 min post-pacing in males, but not females. Despite an identical DP intervention, rhizotomy treated male animals did not exhibit a sustained increase in tidal volume or EMG amplitude. Our data suggests that DP induces phrenic afferent dependent plasticity characterized by a long-lasting increase in tidal volume and diaphragm EMG amplitude in awake male rodents following cSCI.