The Calcium Channel Blocker Nimodipine Inhibits Spinal Reflex Pathways in Humans

The Effect of Calcium Channel Blocker Nimodipine on Human Spinal Reflex Pathways

Academic Background

Motor control is one of the essential functions of the nervous system, and spinal reflex pathways play a key role in this process. In animal studies, voltage-sensitive calcium channels (VSCCs) have been identified as critical factors in regulating the excitability of motor neurons and interneurons. However, the role of these channels in human motor control remains incompletely understood, particularly their potential in treating spasticity. Spasticity is a common neurological dysfunction often associated with conditions such as spinal cord injury, stroke, and multiple sclerosis. Currently, commonly used antispastic drugs like baclofen, although effective, have limitations due to their side effects and long-term efficacy.

Therefore, this study aims to investigate the acute effects of the calcium channel blocker Nimodipine on human spinal reflex pathways and, through comparison with baclofen, evaluate its potential as a future antispastic treatment. Nimodipine is an L-type calcium channel (LTCC) blocker approved by the FDA and EMA, known for its favorable pharmacokinetics and minimal side effects. By examining the effects of Nimodipine on the H-reflex, stretch reflex, and cutaneous reflex, this study seeks to uncover its mechanism of action at the spinal level and provide a foundation for future clinical treatments.

Source of the Paper

This paper was co-authored by Eva Rudjord Therkildsen from the Department of Neuroscience at the University of Copenhagen, Jens Bo Nielsen, who is also affiliated with the Elsass Foundation, and Jakob Lorentzen from the Department of Pediatrics at Rigshospitalet, Copenhagen. The research paper was first published on December 20, 2025, in the Journal of Neurophysiology, with the DOI 10.1152/jn.00585.2024.

Research Process

This study employed a double-blind crossover design, recruiting 19 healthy subjects (mean age 32 years, 8 males, 11 females). Participants received interventions of Nimodipine (60 mg tablet) and baclofen (25 mg tablet) on two separate days, with measurements of spinal reflexes taken before and at 30, 60, and 90 minutes post-intervention. Reflex measurements included the soleus stretch reflex, H-reflex, and tibialis anterior cutaneous reflex.

Specific Experimental Procedures:

  1. H-reflex Measurement: Electrical stimulation of the tibial nerve in the popliteal fossa elicited the soleus H-reflex and M-wave (direct motor response). The ratio of the maximum H-reflex to the maximum M-wave (Hmax/Mmax ratio) was used to assess spinal reflex excitability.

  2. Stretch Reflex Measurement: A computer-controlled footplate rapidly stretched the plantar flexors (soleus muscle) of the ankle, and the electromyographic response of the stretch reflex was recorded. The stretch reflex was analyzed in both resting and pre-contraction states, with reflex components (M1, M2, M3) identified.

  3. Cutaneous Reflex Measurement: Electrical stimulation of the sural nerve elicited the cutaneous reflex of the tibialis anterior muscle during pre-contraction. Typical cutaneous reflexes included early inhibition followed by facilitation.

Data analysis utilized a one-way repeated-measures ANOVA to evaluate changes pre- and post-intervention, with Geisser-Greenhouse correction applied to address violations of sphericity assumptions.

Key Findings

  1. Changes in the H-reflex: Nimodipine significantly reduced the Hmax/Mmax ratio (p < 0.0001), with an average decrease of 12.5% to 15.5%. Baclofen showed a similar but weaker effect (p = 0.024), with an average decrease of 7.92% to 11.7%. The amplitude of the M-wave remained unchanged under both interventions, indicating that Nimodipine’s effects were primarily at the spinal level rather than peripheral nerves.

  2. Changes in the Stretch Reflex: Nimodipine significantly reduced the soleus stretch reflex in the resting state (p = 0.0073), but no significant changes were observed during pre-contraction. Baclofen’s effect on the stretch reflex did not reach statistical significance (p = 0.083).

  3. Changes in the Cutaneous Reflex: Nimodipine showed a trend toward reducing early inhibition and subsequent facilitation, though the results were not statistically significant (p = 0.050 and p = 0.065, respectively). Baclofen exhibited a similar trend in its effects on the cutaneous reflex.

Conclusions and Implications

This study demonstrates that Nimodipine significantly reduces the H-reflex and stretch reflex in healthy individuals at rest but does not significantly affect the stretch reflex during pre-contraction. This suggests that Nimodipine may reduce spinal reflex excitability by inhibiting persistent inward currents (PICs) in spinal interneurons or motor neurons. However, the lack of effect during pre-contraction indicates that voluntary motor activity can counteract Nimodipine’s inhibitory effects.

Compared to baclofen, Nimodipine showed stronger effects in reducing spinal reflex excitability, particularly in the H-reflex and stretch reflex. These findings provide preliminary evidence for Nimodipine’s potential as a future antispastic treatment. Additionally, Nimodipine’s safety profile was favorable, with no severe side effects reported in the study.

Research Highlights

  1. Innovative Methodology: This study is the first to systematically evaluate the effects of Nimodipine on multiple spinal reflex pathways in healthy humans, comparing it to baclofen and providing initial evidence for its potential as an antispastic treatment.

  2. Mechanism of Calcium Channel Blockers: By revealing Nimodipine’s inhibitory effects on spinal reflexes, this study offers new insights into the role of calcium channels in human motor control.

  3. Clinical Application Potential: Nimodipine’s safety and significant suppression of spinal reflexes provide a theoretical foundation for its use in spasticity treatment.

Additional Valuable Information

The authors also note the limitations of the study, such as the absence of a placebo control group and the possibility that reflex changes in healthy individuals may differ from those in spastic patients. Future research should further explore the effects of Nimodipine in spastic patients and incorporate more precise physiological measurements (e.g., spinal electrophysiological recordings) to validate its mechanism of action.

This study not only provides scientific evidence for Nimodipine as an antispastic treatment but also opens new research directions for understanding the regulatory role of calcium channels in human spinal reflexes.