Spinal cord injury (SCI) at any level that interrupts ascending or descending pathways between the lumbosacral spinal cord and the pontine micturition center can exert a profound negative impact on lower urinary tract (LUT) function, which results in problems with both urine storage and emptying of the bladder. The functional consequences include neurogenic detrusor over-activity (NDO), high bladder pressures (BP), detrusor-sphincter dyssynergia (DSD), inefficient voiding, and urine retention that are associated with a high degree of morbidity and a poor quality of life. Previous and ongoing studies in our laboratory have focused on the use of neuroplasticity-inducing acute intermittent hypoxia (AIH) as a therapeutic strategy to improve bladder function following clinically relevant moderate contusion SCI. While this work shows that a single AIH exposure can produce an immediate long-lasting (up to 120 min post-AIH) reduction in NDO (a.k.a., non-voiding bladder contractions, NVCs) and DSD (i.e., improved bladder-sphincter coordination) and more efficient voiding, the mechanism(s) underlying these AIH-induced beneficial improvements remains to be determined. AIH-induced neural plasticity, which is best studied in the respiratory neural control system, has been shown to be dominated by activation of serotonin (5-HT) receptors that promote de novo synthesis of BDNF and activation of high affinity TrkB receptors (referred to as the Q pathway). The goal of the current study was to determine whether a 5-HT-dependent mechanism contributes to AIH-induced improvements in LUT function. To begin to address this possibility, we first examined the effects of AIH3x5min or AIH5x3min (12% O 2 ) administered at 20-30 min after systemic injection of the broad spectrum 5-HT receptor antagonist methysergide (MSD; 4 mg/kg, iv) on reflex bladder function measured by continuous infusion cystometry in pilot experiments conducted in urethane-anesthetized naïve adult female rats, and found that pre-treatment with MSD markedly impaired development/expression of AIH-induced improvements/changes in reflex bladder behaviors. We then conducted a similar series of preliminary experiments at 4-weeks after mid-thoracic moderate contusion SCI and found that pre-treatment with MSD impaired/eliminated AIH-induced beneficial improvements in reflex bladder behaviors, bladder-EUS (sphincter) coordination behaviors, and volume-related voiding features. To determine whether lumbosacral spinal cord regions controlling somatic and autonomic LUT functions contributed, we conducted a final series of preliminary experiments at 4-weeks after moderate contusion SCI in which intrathecal injection of MSD (300µg/kg; 20mM, 15µl) at the ventrolateral L4-S2 level was used, and found that blockade of 5-HT receptors at this level similarly impaired/eliminated AIH-induced beneficial improvements in reflex bladder behaviors, bladder-EUS (sphincter) coordination behaviors, and volume-related voiding features. We interpret these findings to indicate that a 5-HT-dependent mechanism contributes, at least in part, to induction of AIH-mediated beneficial effects on LUT function Support: NYS DOH SCIRB C37711GG This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Solomon et al. (Fri,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: