Effects of Serotonergic Medications on Locomotor Performance in Humans with Incomplete Spinal Cord Injury

Abstract

Incomplete spinal cord injury (iSCI) often results in significant motor impairments that lead to decreased functional mobility. Loss of descending serotonergic (5HT) input to spinal circuits is thought to contribute to motor impairments, with enhanced motor function demonstrated through augmentation of 5HT signaling. However, the presence of spastic motor behaviors in SCI is attributed, in part, to changes in spinal 5HT receptors that augment their activity in the absence of 5HT, although data demonstrating motor effects of 5HT agents that deactivate these receptors are conflicting. The effects of enhancement or depression of 5HT signaling on locomotor function have not been thoroughly evaluated in human iSCI. Therefore, the aim of the current study was to investigate acute effects of 5HT medications on locomotion in 10 subjects with chronic ( > 1 year) iSCI. Peak overground and treadmill locomotor performance, including measures of gait kinematics, electromyographic (EMG) activity, and oxygen consumption, were assessed before and after single-dose administration of either a selective serotonin reuptake inhibitor (SSRI) or a 5HT antagonist using a double-blinded, randomized, cross-over design. Results indicate that neither medication led to improvements in locomotion, with a significant decrease in peak overground gait speed observed after 5HT antagonists (from 0.8 -0.1 to 0.7 -0.1 m/s; p = 0.01). Additionally, 5-HT medications had differential effects on EMG activity, with 5HT antagonists decreasing extensor activity and SSRIs increasing flexor activity. Our data therefore suggest that acute manipulation of 5HT signaling, despite changes in muscle activity, does not improve locomotor performance after iSCI.

Increased Lower Limb Spasticity but Not Strength or Function Following a Single-Dose Serotonin Reuptake Inhibitor in Chronic Stroke

“…Regardless, the present data are consistent with selected studies in animal models 52 and humans of neurologic injury (SCI) 51 indicating no immediate improvements in locomotion function with single-dose enhancement of 5-HT transmission. These findings are of clinical interest because previous data suggest improvements in motor function after prolonged SSRI use, although greater changes were observed in upper versus lower limbs.…”

“…While locomotion is associated with increased 5-HT activity, the nonsignificant increases in strength with significant gains in spasticity could have limited functional performance. More detailed biomechanical and electromyographic analyses during walking after SSRIs are necessary to identify specific locomotor changes, 51 accessed by following the link in the citation at the bottom of the page.…”

Sample sizes and statistical methods in interventional studies on individuals with spinal cord injury: A systematic review

“…Different implications thereof were mentioned, ranging from considerable baseline variability, which could not be accounted for, to limited generalizability of the results, decreased power, and the need for replication in larger samples . Seventeen studies (10%) stated a rule‐of‐thumb like justification for the choice of a particular statistical approach, mainly that nonparametric methods were used instead of parametric approaches due to the small sample size . However, no study was found where the authors provided a theoretically sound reason (eg, by referring to a simulation study, which indicates a good performance in small sample settings).…”

“…46,47 Seventeen studies (10%) stated a rule-of-thumb like justification for the choice of a particular statistical approach, mainly that nonparametric methods were used instead of parametric approaches due to the small sample size. [48][49][50][51][52][53][54][55] However, no study was found where the authors provided a theoretically sound reason (eg, by referring to a simulation study, which indicates a good performance in small sample settings).…”

BDNF Overexpression Exhibited Bilateral Effect on Neural Behavior in SCT Mice Associated with AKT Signal Pathway

“…The cDNA was 10-fold serially diluted to seven concentrations for the standard curve. sensory and motor function is also not satisfaction [4,5]. Hence, it is also attractive to study on the mechanism of SCI to find the valid strategy for further functional recovery.…”