Characterizing preserved autonomic regulation following spinal cord injury: Methods of a novel concerted testing battery and illustrative examples of a new translationally focused data representation.

Autonomic dysfunction is common after spinal cord injury, though differing from motor and sensory function, there are currently no established batteries of tests to comprehensively characterize these deficits. Further, while individual established autonomic tests have a long history and sound scientific background, translating these autonomic testing results to inform clinical understanding is a major barrier. Herein, we outline a battery of six laboratory autonomic tests which were carefully curated to collectively describe the ability of individuals with spinal cord injury to inhibit and recruit sympathetic activity through the injured spinal cord. Presenting normative control data in 23 uninjured individuals completing this testing battery, we further demonstrate the utility of extracting three key testing metrics for each test, comparing these control results to 11 individuals with spinal cord injury. Results demonstrate strong normality of data with testing psychometrics suggesting reliable reproducibility on repeat testing. Further, even in this preliminary sample of individuals with spinal cord injuries, clear differences begin to emerge. This illustrates the ability of this collective testing battery to characterize autonomic regulation after spinal cord injury. To aid in clinical translation, we further present a graphical representation, an autonomic phenotype, which serves as a snapshot of how normal or abnormal sympathetic inhibition and recruitment of activation may be after spinal cord injury. Utilizing these autonomic phenotypes, three example cases of individuals with spinal cord injury highlight evidence of varied degrees of autonomically complete spinal cord injury. Together, this represents a key advancement in our understanding of autonomic function after spinal cord injury.

Valsalva maneuver pressure recovery time is prolonged following spinal cord injury with correlations to autonomically-influenced secondary complications.

PURPOSE: This work's purpose was to quantify rapid sympathetic activation in individuals with spinal cord injury (SCI), and to identify associated correlations with symptoms of orthostatic hypotension and common autonomically mediated secondary medical complications. METHODS: This work was a cross-sectional study of individuals with SCI and uninjured individuals. Symptoms of orthostatic hypotension were recorded using the Composite Autonomic Symptom Score (COMPASS)-31 and Autonomic Dysfunction following SCI (ADFSCI) survey. Histories of secondary complications of SCI were gathered. Rapid sympathetic activation was assessed using pressure recovery time of Valsalva maneuver. Stepwise multiple linear regression models identified contributions to secondary medical complication burden. RESULTS: In total, 48 individuals (24 with SCI, 24 uninjured) underwent testing, with symptoms of orthostatic hypotension higher in those with SCI (COMPASS-31, 3.3 versus 0.6, p < 0.01; ADFSCI, 21.2 versus. 3.2, p < 0.01). Pressure recovery time was prolonged after SCI (7.0 s versus. 1.7 s, p < 0.01), though poorly correlated with orthostatic symptom severity. Neurological level of injury after SCI influenced pressure recovery time, with higher injury levels associated with more prolonged time. Stepwise multiple linear regression models identified pressure recovery time as the primary explanation for variance in number of urinary tract infections (34%), histories of hospitalizations (12%), and cumulative secondary medical complication burden (24%). In all conditions except time for bowel program, pressure recovery time outperformed current clinical tools for assessing such risk. CONCLUSIONS: SCI is associated with impaired rapid sympathetic activation, demonstrated here by prolonged pressure recovery time. Prolonged pressure recovery time after SCI predicts higher risk for autonomically mediated secondary complications, serving as a viable index for more "autonomically complete" injury.

Cardiorespiratory Effects of Yogic Versus Slow Breathing in Individuals with a Spinal Cord Injury: An Exploratory Cohort Study.

Background: An intricate physiological and pathophysiological connection exists between the heart and lungs, which is especially important in individuals with spinal cord injury (SCI). While an exercise intervention may seem the best approach to leverage this relationship, the prior work has shown that, despite numerous health benefits, regular exercise training does not improve cardiorespiratory control in individuals with SCI. Breath training presents an alternative intervention that is uniquely accessible, with yogic breathing directly engaging linked fluctuations in respiration and cardiovascular control. In addition, there is evidence across a range of populations that regular yogic breathing reduces cardiovascular disease risk. It is possible that the chronic decrease in breathing frequency associated with regular yogic breathing, rather than the specific yogic breathing techniques themselves, is the primary contributor to the observed risk reduction. Methods: Therefore, in 12 individuals with traumatic SCI from C4 to T8, the authors compared Unpaced and conventional 0.083 Hz (Slow) paced breathing with various yogic breathing techniques including: (1) inspiratory-expiratory breath holds (i.e., Kumbhaka or "Box Breathing"), (2) extended exhalation (1:2 duty cycle), and (3) expiratory resistance via throat constriction (i.e., Ujjayi). Beat-to-beat heart rate and blood pressure were measured as well as end-tidal CO2 and O2 saturation were measured. Statistical analysis was performed using a one-way repeated-measures analysis of variance with post hoc pairwise t tests corrected for multiple comparisons. Results: As expected, all slow breathing patterns markedly increased respiratory sinus arrhythmia (RSA) compared with Unpaced in all (n = 12) individuals. More importantly, Ujjayi breathing appeared to improve ventilatory efficiency over Unpaced breathing in individuals with SCI by increasing O2 saturation (97.6% vs. 96.1%; p = 0.042) and tended to decrease end-tidal CO2 (32 mmHg vs. 35 mmHg; p = 0.08). While other slow breathing patterns demonstrated similar effects, only Ujjayi improved RSA while increasing heart rate and improving ventilatory efficiency. Conclusions: Hence, slow breathing per se can result in important cardiorespiratory changes, but the yogic breathing practice of Ujjayi, with glottic throat resistance, may hold the greatest promise for improving cardiorespiratory control in individuals with SCI (CTR ID No. NCT05480618).

Paradoxical breathing during sleep is associated with increased sleep apnea and reduced ventilatory capacities in high-level spinal cord injury.

Sleep-disordered breathing is highly prevalent in individuals with high-level spinal cord injury. In addition, chest mechanics are known to be altered, leading to paradoxical breathing. Here we investigated the interaction between paradoxical breathing and sleep quality in these patients, and its association with measurements of respiratory function, hypercapnic ventilatory response and peak exercise ventilation. Home-based polysomnography was performed in 13 patients with spinal cord injury (C4 to T4) untreated for sleep-disordered breathing. We defined paradoxical breathing as counterphase between thoracic and abdominal movements during slow-wave and rapid eye movement sleep. Sleep quality, pulmonary function, hypercapnic ventilatory responses and peak exercise ventilation were compared between those with and without paradoxical breathing. Half of individuals presented with nocturnal paradoxical breathing. Despite similar age, body mass index, injury level, time since injury, and respiratory function, those with paradoxical breathing had higher apnea-hypopnea index (13 ± 8 versus 5 ± 3 events per hr) and average sleep heart rate (67 ± 12 versus 54 ± 4 bpm; p < 0.05). Moreover, paradoxical breathing was associated with lower hypercapnic ventilatory response (slope: 0.35 ± 0.17 versus 0.96 ± 0.38) and lower peak exercise ventilation (33 ± 4 versus 48 ± 12 L min-1 ; p < 0.05). Nocturnal respiratory muscle desynchronization could play a role in the pathophysiology of sleep apnea, and could relate to low ventilatory responses to both hypercapnia and exercise in high-level spinal cord injury. Polysomnography may be an important diagnostic tool for these patients for whom therapeutic approaches should be considered to treat this abnormality.

Transcutaneous spinal cord stimulation and its impact on cardiovascular autonomic regulation after spinal cord injury.

Individuals with spinal cord injury (SCI) have significant dysfunction in cardiovascular autonomic regulation. Although recent findings postulate that spinal cord stimulation improves autonomic regulation, limited scope of past methods have tested only above level sympathetic activation, leaving significant uncertainty. To identify whether transcutaneous spinal cord stimulation improves cardiovascular autonomic regulation, two pairs of well-matched individuals with and without high thoracic, complete SCI were recruited. Baseline autonomic regulation was characterized with multiple tests of sympathoinhibition and above/below injury level sympathoexcitation. At three subsequent visits, testing was repeated with the addition submotor threshold transcutaneous spinal cord stimulation at three previously advocated frequencies. Uninjured controls demonstrated no autonomic deficits at baseline and had no changes with any frequency of stimulation. As expected, individuals with SCI had baseline autonomic dysfunction. In a frequency-dependent manner, spinal cord stimulation enhanced sympathoexcitatory responses, normalizing previously impaired Valsalva's maneuvers. However, stimulation exacerbated already impaired sympathoinhibitory responses, resulting in significantly greater mean arterial pressure increases with the same phenylephrine doses compared with baseline. Impaired sympathoexcitatory response below the level of injury were also further exacerbated with spinal cord stimulation. At baseline, neither individual with SCI demonstrated autonomic dysreflexia with the noxious foot cold pressor test; the addition of stimulation led to a dysreflexic response in every trial, with greater relative hypertension and bradycardia indicating no improvement in cardiovascular autonomic regulation. Collectively, transcutaneous spinal cord stimulation demonstrates no improvements in autonomic regulation after SCI, and instead likely generates tonic sympathoexcitation which may lower the threshold for dangerous autonomic dysreflexia.NEW & NOTEWORTHY Spinal cord stimulation increases blood pressure after spinal cord injury, though it is unclear if this restores natural autonomic regulation or induces a potentially dangerous pathological reflex. We performed comprehensive autonomic testing batteries, with and without transcutaneous spinal cord stimulation at multiple frequencies. Across 96 independent tests, stimulation did not change uninjured control responses, though all frequencies facilitated pathological reflexes without improved autonomic regulation for those with spinal cord injuries.

Nitric oxide-mediated vasodilation in human bone.

OBJECTIVE: Regulation of blood flow to bone is critical but poorly understood, particularly in humans. This study aims to determine whether nitric oxide (NO), a major regulator of vascular tone to other tissues, contributes also to the regulation of blood flow to bone. METHODS: In young healthy adults (n = 16, 8F, 8M), we characterized NO-mediated vasodilation in the tibia in response to sublingual nitroglycerin and contrasted it to lower leg. Blood flow responses were assessed in supine individuals by continuously measuring tibial total hemoglobin (tHb) via near-infrared spectroscopy and lower leg blood flow (LBF) as popliteal flow velocity via Doppler ultrasound in the same leg. RESULTS: LBF increased by Δ9.73 ± 0.66 cm/s and peaked 4.4 min after NO administration and declined slowly but remained elevated (Δ3.63 ± 0.60 cm/s) at 10 min. In contrast, time to peak response was longer and smaller in magnitude in the tibia as tHb increased Δ2.08 ± 0.22 µM and peaked 5.3 min after NO administration and declined quickly but remained elevated (Δ0.87±0.22 µM) at 10 min (p = .01). CONCLUSIONS: In young adults, the tibial vasculature demonstrates robust NO-mediated vasodilation, but tHb is delayed and diminishes faster compared to LBF, predominately reflective of skeletal muscle responses. Thus, NO-mediated vasodilation in bone may be characteristically different from other vascular beds.

Patient Perceptions and Clinical Assessments of Cardiometabolic Disease After Subacute Spinal Cord Injury.

OBJECTIVES: To investigate the effectiveness of health care team communication regarding cardiometabolic disease (CMD) risk factors with patients with subacute spinal cord injury (SCI). DESIGN: Multi-site prospective cross-sectional study. SETTING: Five National Institute on Disability, Independent Living, and Rehabilitation Research Model SCI Rehabilitation Centers. PARTICIPANTS: Ninety-six patients with subacute SCI, aged 18-70 years, with SCI (neurologic levels of injury C2-L2, American Spinal Injury Association Impairment Scale grades A-D), and enrolled within 2 months of initial rehabilitation discharge (N=96). INTERVENTIONS: None. MAIN OUTCOME MEASURE(S): Objective risk factors of CMD (body mass index, fasting glucose, insulin, high-density lipoprotein cholesterol, triglyceride levels, and resting blood pressure). Patient reported recall of these present risk factors being shared with them by their health care team. Medications prescribed to patients to address these present risk factors were checked against guideline- assessed risk factors. RESULTS: Objective evidence of 197 CMD risk factors was identified, with patients recalling less than 12% of these (P<.0001) being shared with them by their health care team. Thirty-one individuals (32%) met criteria for a diagnosis of CMD, with only 1 of these patients (3.2%) recalling that this was shared by their health care team (P<.0001). Pharmacologic management was prescribed to address these risk factors only 7.2% of the time. CONCLUSIONS: Despite high prevalence of CMD risk factors after acute SCI, patients routinely do not recall being told of their present risk factors. Multifaceted education and professionals' engagement efforts are needed to optimize treatment for these individuals.

Vascular deficits contributing to skeletal fragility in type 1 diabetes.

Over 1 million Americans are currently living with T1D and improvements in diabetes management have increased the number of adults with T1D living into later decades of life. This growing population of older adults with diabetes is more susceptible to aging comorbidities, including both vascular disease and osteoporosis. Indeed, adults with T1D have a 2- to 3- fold higher risk of any fracture and up to 7-fold higher risk of hip fracture compared to those without diabetes. Recently, diabetes-related vascular deficits have emerged as potential risks factors for impaired bone blood flow and poor bone health and it has been hypothesized that there is a direct pathophysiologic link between vascular disease and skeletal outcomes in T1D. Indeed, microvascular disease (MVD), one of the most serious consequences of diabetes, has been linked to worse bone microarchitecture in older adults with T1D compared to their counterparts without MVD. The association between the presence of microvascular complications and compromised bone microarchitecture indicates the potential direct deleterious effect of vascular compromise, leading to abnormal skeletal blood flow, altered bone remodeling, and deficits in bone structure. In addition, vascular diabetic complications are characterized by increased vascular calcification, decreased arterial distensibility, and vascular remodeling with increased arterial stiffness and thickness of the vessel walls. These extensive alterations in vascular structure lead to impaired myogenic control and reduced nitric-oxide mediated vasodilation, compromising regulation of blood flow across almost all vascular beds and significantly restricting skeletal muscle blood flow seen in those with T1D. Vascular deficits in T1D may very well extend to bone, compromising skeletal blood flow control, and resulting in reduced blood flow to bone, thus negatively impacting bone health. Indeed, several animal and ex vivo human studies report that diabetes induces microvascular damage within bone are strongly correlated with diabetes disease severity and duration. In this review article, we will discuss the contribution of diabetes-induced vascular deficits to bone density, bone microarchitecture, and bone blood flow regulation, and review the potential contribution of vascular disease to skeletal fragility in T1D.

Calculation of Tissue Oxygenation via an Inverse Boundary Problem for Transcutaneous Oxygenation Wearable Applications.

In this article, we present a toolset to fully leverage a previously developed transcutaneous oxygenation monitor (TCOM) wearable technology to accurately measure skin oxygenation values. We describe numerical models and experimental characterization techniques that allow for the extraction of precise tissue oxygenation measurements. The numerical model is based on an inverse boundary problem of the parabolic equation with Dirichlet boundary conditions. To validate this model and characterize the diffusion of oxygen through the oxygen sensing materials, we designed a series of control/calibration experiments modeled after the device's clinical application using oxygenation values in the physiological range expected for healthy tissue. Our results demonstrate that it is possible to obtain accurate tissue pO2 measurements without the need for long equilibration times with a small wearable device.

The Impact of Transcutaneous Spinal Cord Stimulation on Autonomic Regulation after Spinal Cord Injury: A randomized crossover trial.

Importance: Individuals with spinal cord injury (SCI) have significant autonomic nervous system dysfunction. However, despite recent findings postulated to support that spinal cord stimulation improves dynamic autonomic regulation, limited scope of previous testing means the true effects remain unknown. Objective: To determine whether transcutaneous spinal cord stimulation improves dynamic autonomic regulation after SCI. Design: Single-blinded, randomized crossover trial with matched cohorts. Setting: Academic autonomic physiology laboratory. Participants: Two pairs of well-matched individuals with and without high-thoracic, complete SCI. Interventions: Sub-motor threshold transcutaneous spinal cord stimulation delivered at T10-T11 using 120Hz, 30Hz, and 30Hz with 5kHz carrier frequency at separate autonomic testing sessions. Main Outcomes and Measures: Baseline autonomic regulation was characterized with tests of above injury level sympathoexcitation (Valsalva's maneuver), sympathoinhibition (progressive doses of bolus intravenous phenylephrine), and below level sympathoexcitation (foot cold pressor test). At three subsequent visits, this testing battery was repeated with the addition of spinal cord stimulation at each frequency. Changes in autonomic regulation for each frequency were then analyzed relative to baseline testing for each individual and within matched cohorts. Results: Uninjured controls demonstrated no autonomic deficits at baseline and had no changes with any frequency of stimulation. Contrasting this, and as expected, individuals with SCI had baseline autonomic dysfunction. In a frequency-dependent manner, spinal cord stimulation enhanced sympathoexcitatory responses, normalizing previously impaired Valsalva's maneuvers. However, stimulation exacerbated already impaired sympathoinhibitory responses, resulting in significantly greater mean arterial pressure increases with the same phenylephrine doses compared to baseline. Impaired sympathoexcitatory response below the level of injury were also further exacerbated with spinal cord stimulation. At baseline, neither individual with SCI demonstrated autonomic dysreflexia with the noxious foot cold pressor test; the addition of stimulation led to a dysreflexic response in every trial, with greater relative hypertension and bradycardia indicating no improvement in autonomic regulation. Conclusions and Relevance: Transcutaneous spinal cord stimulation does not improve autonomic regulation after SCI, and instead likely generates tonic, frequency-dependent sympathoexcitation which may lower the threshold for autonomic dysreflexia.

Digital Interventions for Social Participation in Adults with Long-term Physical Conditions: A Systematic Review.

This review aims to identify and evaluate digital interventions for social participation in the growing population of adults with long-term physical conditions. Articles were sourced from MEDLINE, EMBASE, CINAHL and PsycINFO databases using subject headings and keywords related to "social participation" and "digital technology". Studies that adopted digital technology interventions to improve social participation in adults with long-term physical conditions were included. Data on study methodology, participant and digital intervention characteristics, and findings related to social participation were extracted. The search yielded a total of 4646 articles and 14 articles met criteria for final review with five randomized controlled trials, two non-randomized clinical trials and seven one-group pretest-posttest clinical trials. Studies were organized based on the digital intervention strategy implemented to improve social participation: group support (n = 4), individual skill training or counseling (n = 6), education and support (n = 3), and mixed intervention (n = 1). The group support interventions developed a social network among participants through videoconference, app, or virtual reality platform. Three studies reported positive improvements in different aspects of social participation. Individual skill training or counseling mainly utilized phone calls to help participants cope with activity participation and interpersonal relationship issues. Only two studies demonstrated benefits for social participation. The education and support intervention, which used messages and website information to increase participants' knowledge and provide support, showed positive findings in three studies. This review suggests digital interventions for improving social participation in adults with long-term physical conditions are feasible and the effectiveness of different strategies may vary.Registration: This review was prospectively registered on the International Prospective Register of Systematic Reviews (PROSPERO) (registry number: CRD42021254105).

Improved pulmonary function is associated with reduced inflammation after hybrid whole-body exercise training in persons with spinal cord injury.

NEW FINDINGS: What is the central question of this study? Does 12 weeks of functional electrical stimulation (FES) rowing exercise training lead to suppressed systemic inflammation and an improvement in pulmonary function in persons with sub-acute spinal cord injury (SCI)? What is the main finding and its importance? Twelve weeks of FES rowing exercise improves pulmonary function and the magnitude of improvement is associated with reductions in inflammatory biomarkers. Thus, interventions targeting inflammation may lead to better pulmonary outcomes for person with sub-acute SCI. ABSTRACT: The current study was designed to test the hypotheses that (1) reducing systemic inflammation via a 12-week functional electrical stimulation rowing exercise training (FESRT) prescription results in augmented pulmonary function, and (2) the magnitude of improvement in pulmonary function is inversely associated with the magnitude of systemic inflammation suppression in persons with sub-acute (≤2 years) spinal cord injury (SCI). We conducted a retrospective analysis of a randomized controlled trial (NCT#02139436). Twenty-one participants were enrolled (standard of care (SOC; n = 9) or FESRT (n = 12)). The exercise prescription was three sessions/week at 70-85% of peak heart rate. A two-way analysis of covariance and regression analysis was used to assess group differences and associations between pulmonary function, log transformed high-sensitivity C-reactive protein (hsCRPlog ) and white blood cell count (WBC). Following FESRT, clinically significant improvements in forced expiratory volume in 1 s (FEV1 ; 0.25 (0.08-0.43) vs. -0.06 (-0.26 to 0.15) litres) and forced vital capacity (0.22 (0.04-0.39) vs. 0.08 (-0.29 to 0.12) litres) were noted and systemic WBC (-1.45 (-2.48 to -0.50) vs. 0.41 (-0.74 to 1.56) µl) levels were suppressed compared to SOC (mean change (95% confidence interval); P < 0.05). Additionally, both ΔhsCRPlog and ΔWBC were predictors of ΔFEV1 (r2  = 0.89 and 0.43, respectively; P < 0.05). Twelve weeks of FESRT improves pulmonary function and reduces WBC in persons with sub-acute SCI. The potency of FESRT to augment pulmonary function may depend on adequate suppression of systemic inflammation.

Exercise Training Does Not Attenuate Cardiac Atrophy or Loss of Function in Individuals With Acute Spinal Cord Injury: A Pilot Study.

OBJECTIVE: To investigate the effects of 2 modes of exercise training, upper-body alone, and the addition of electrical stimulation of the lower body, to attenuate cardiac atrophy and loss of function in individuals with acute spinal cord injury (SCI). DESIGN: Randomized controlled trial. SETTING: Rehabilitation Hospital. PARTICIPANTS: Volunteers (N=27; 5 women, 22 men) who were <24 months post SCI. INTERVENTIONS: Volunteers completed either 6 months of no structured exercise (Control), arm rowing (AO), or a combination of arm rowing with electrical stimulation of lower body paralyzed muscle (functional electrical stimulation [FES] rowing). MAIN OUTCOME MEASURES: Transthoracic echocardiography was performed on each subject prior to and 6 months after the intervention. The relations between time since injury and exercise type to cardiac structure and function were assessed via 2-way repeated-measures analysis of variance and with multilevel linear regression. RESULTS: Time since injury was significantly associated with a continuous decline in cardiac structure and systolic function, specifically, a reduction in left ventricular mass (0.197 g/month; P=.049), internal diameter during systole (0.255 mm/month; P<.001), and diastole (0.217 mm/month; P=.019), as well as cardiac output (0.048 L/month, P=.019), and left ventricular percent shortening (0.256 %/month; P=.027). These associations were not differentially affected by exercise (Control vs AO vs FES, P>.05). CONCLUSIONS: These results indicate that within the subacute phase of recovery from SCI there is a linear loss of left ventricular cardiac structure and systolic function that is not attenuated by current rehabilitative aerobic exercise practices. Reductions in cardiac structure and function may increase the risk of cardiovascular disease in individuals with SCI and warrants further interventions to prevent cardiac decline.

Relationship of cardiometabolic disease risk factors with age and spinal cord injury duration.

CONTEXT/OBJECTIVES: Cardiometabolic disease (CMD) is increased after spinal cord injury (SCI), with an increased number of CMD risk factors that relate to higher mortality. The study objective was to characterize the relationship of age and injury duration with CMD. DESIGN: Retrospective cohort assessment of CMD risks using unbiased recursive partitioning to divide for group comparison: (1) Lowest Risk, (2) Moderate Risk, and (3) Highest Risk based on classification and regression trees predicting CMD diagnosis by age and injury duration. SETTING: Academic rehabilitation center laboratory. PARTICIPANTS: Adults (N = 103; aged 18-75) with traumatic SCI (C4-L2) of 3 months to 42 years duration. INTERVENTIONS: NA. OUTCOME MEASURES: CMD risk factors (obesity, insulin resistance, dyslipidemia, and hypertension) using Paralyzed Veterans of America SCI-specific guidelines. RESULTS: Obesity was prevalent (82%) and co-occurred with most other risk factors present. Age increased odds for CMD diagnosis by 1.05 per year (P = 0.02) and was directly related to elevated body mass index (BMI, ß = 0.42, P < 0.05), fasting glucose (ß = 0.58, P < 0.01), and higher systolic blood pressure (ß = 0.31, P < 0.10). In contrast, time since injury contributed to lower risk factor count (ß = -0.29, P < 0.10) and higher HDL-C (ß = 0.50, P < 0.01), and was not related to odds of CMD diagnosis. CONCLUSION: While SCI is linked to an increased risk of CMD, age is associated with higher CMD risk. Increased SCI duration related to improvement in individual CMD risk factors but did not decrease overall risk for CMD diagnosis. SCI may not uniformly increase CMD risks and highlight a necessary focus on weight management for risk prevention.

Serotonin 1A Receptor Pharmacotherapy and Neuroplasticity in Spinal Cord Injury.

Spinal cord injury is associated with damage in descending and ascending pathways between brainstem/cortex and spinal neurons, leading to loss in sensory-motor functions. This leads not only to locomotor reduction but also to important respiratory impairments, both reducing cardiorespiratory engagement, and increasing cardiovascular risk and mortality. Moreover, individuals with high-level injuries suffer from sleep-disordered breathing in a greater proportion than the general population. Although no current treatments exist to restore motor function in spinal cord injury (SCI), serotoninergic (5-HT) 1A receptor agonists appear as pharmacologic neuromodulators that could be important players in inducing functional improvements by increasing the activation of spared motoneurons. Indeed, single therapies of serotoninergic 1A (5-HT1A) agonists allow for acute and temporary recovery of locomotor function. Moreover, the 5-HT1A agonist could be even more promising when combined with other pharmacotherapies, exercise training, and/or spinal stimulation, rather than administered alone. In this review, we discuss previous and emerging evidence showing the value of the 5HT1A receptor agonist therapies for motor and respiratory limitations in SCI. Moreover, we provide mechanistic hypotheses and clinical impact for the potential benefit of 5-HT1A agonist pharmacology in inducing neuroplasticity and improving locomotor and respiratory functions in SCI.