Attenuation of the pulmonary chemoreflex following acute cervical spinal cord injury

Journal of Applied Physiology

2015

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Unilateral cervical spinal cord hemisection (i.e., C2Hx) usually interrupts the bulbospinal respiratory pathways and results in respiratory impairment. It has been demonstrated that activation of the serotonin system can promote locomotor recovery after spinal cord injury. The present study was designed to investigate whether serotonergic activation can improve respiratory function during the chronic injury state. Bilateral diaphragm electromyogram and tidal volume were measured in anesthetized and spontaneously breathing adult rats at 8 wk post-C2Hx or C2 laminectomy. A bolus intravenous injection of a serotonin precursor [5-hydroxytryptophan (5-HTP), 10 mg/kg], a serotonin reuptake inhibitor (fluoxetine, 10 mg/kg), or a potent agonist for serotonin 2A receptors (TCB-2, 0.05 mg/kg) was used to activate the serotonergic system. Present results demonstrated that 5-HTP and TCB-2, but not fluoxetine, significantly increased the inspiratory activity of the diaphragm electromyogram ipsilateral to the lesion for at least 30 min in C2Hx animals, but not in animals that received sham surgery. However, the tidal volume was not increased after administration of 5-HTP or TCB-2, indicating that the enhancement of ipsilateral diaphragm activity is not associated with improvement of the tidal volume. These results suggest that exogenous activation of the serotonergic system can specifically enhance the ipsilateral diaphragmatic motor outputs, but this approach may not be sufficient to improve respiratory functional recovery following chronic cervical spinal injury.

Section: Spinal Cord Histologymentioning

confidence: 99%

mentioning

confidence: 99%

Effects of serotonergic agents on respiratory recovery after cervical spinal injury

Hsu

Journal of Applied Physiology

2015

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“…The pulmonary chemoreflex is a critical defensive reflex evoked by activation of bronchopulmonary C-fibers. Our recent study (52) demonstrated that pulmonary chemoreflexes induced by intrajugular capsaicin injection was abolished 1 day post-C2Hx. However, it is unknown whether this effect is temporary or remains in the chronic injury phase.…”

mentioning

confidence: 90%

Recovery of the pulmonary chemoreflex and functional role of bronchopulmonary C-fibers following chronic cervical spinal cord injury

Journal of Applied Physiology

Chang

2014

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Persistent impairment of pulmonary defense reflexes is a critical factor contributing to pulmonary complications in patients with spinal cord injuries. The pulmonary chemoreflex evoked by activation of bronchopulmonary C-fibers has been reported to be abolished in animals with acute cervical hemisection (C2Hx). The present study examined whether the pulmonary chemoreflex can recover during the chronic injury phase and investigated the role of bronchopulmonary C-fibers on the altered breathing pattern after C2Hx. In the first protocol, bronchopulmonary C-fibers were excited by intrajugular capsaicin administration in uninjured and complete C2Hx animals 8 wk postsurgery. Capsaicin evoked pulmonary chemoreflexes in both groups, but the reflex intensity was significantly weaker in C2Hx animals. To examine whether spared spinal white matter tissue contributes to pulmonary chemoreflex recovery, the reflex was evaluated in animals with different extents of lateral injury. Linear regression analyses revealed that tidal volume significantly correlated with the extent of spared tissue; however, capsaicin-induced apnea was not related to injury severity when the ipsilateral-to-contralateral white matter ratio was <50%. In the second protocol, the influence of background bronchopulmonary C-fiber activity on respiration was investigated by blocking C-fiber conduction via perivagal capsaicin treatment. The rapid shallow breathing of C2Hx animals persisted after perivagal capsaicin treatment despite attenuation of pulmonary chemoreflexes. These results indicate that the pulmonary chemoreflex can recover to some extent following spinal injury, but remains attenuated even when there is moderate spinal tissue sparing, and that altered breathing pattern of C2Hx animals cannot be attributed to endogenous activation of bronchopulmonary C-fibers.

“…Although bronchopulmonary C‐fibre‐evoked pulmonary chemoreflexes have been extensively reported in many previous studies (Lin & Lee, ; Lee et al . ; Lee & Chang, ; Tsai & Lee, ; Lin et al . ), the influence of capsaicin‐induced bronchopulmonary C‐fibre activation on phrenic motoneuron bursting is poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…Bilateral phrenic nerves display identical inspiratory rhythmic activity under normal conditions; however, lateral cervical spinal cord injury usually interrupts the bulbospinal respiratory pathway and causes cessation of phrenic bursting or diaphragm EMG activity ipsilateral to the lesion (Zhou et al . ; Tsai & Lee, ; Hsu & Lee, ; Navarrete‐Opazo et al . ).…”

Section: Introductionmentioning

confidence: 99%

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

The Journal of Physiology

2016

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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.