Ventral intraspinal microstimulation alters neural population-level nociceptive activity in rats including after spinal cord injury

Jacob Graves McPherson; Maria F Bandres

doi:10.1097/PR9.0000000000001379

Ventral intraspinal microstimulation alters neural population-level nociceptive activity in rats including after spinal cord injury

Pain Rep. 2025 Dec 23;11(1):e1379. doi: 10.1097/PR9.0000000000001379. eCollection 2026 Feb.

Authors

Jacob Graves McPherson^{1

2

3

4

5}, Maria F Bandres^{1

5}

Affiliations

¹ Program in Physical Therapy, Washington University School of Medicine, St. Louis, MO, USA.
² Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, USA.
³ Washington University Pain Center, Washington University School of Medicine, St. Louis, MO, USA.
⁴ Program in Neurosciences, Washington University School of Medicine, St. Louis, MO, USA.
⁵ Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA.

Abstract

Introduction: Spinal cord injury (SCI) often results in movement impairments and neuropathic pain.

Objectives: The purpose of this study was to determine whether intraspinal microstimulation (ISMS) intended to enhance voluntary movement after SCI modulates neural population-level spinal responsiveness to nociceptive sensory input.

Methods: The study was conducted in vivo in 3 cohorts of rats: neurologically intact, chronic SCI without behavioral signs of neuropathic pain, and chronic SCI with neuropathic pain. Nociceptive sensory input was induced by pinches of the plantar surface of the hind paw before, during, and after low frequency (7 Hz), submotor threshold ISMS delivered within or near the motor pools of the L5 spinal segment. Neural population-level responsiveness to nociceptive input was recorded throughout the dorso-ventral extent of the L5 spinal segment using microelectrode arrays.

Results: Before ISMS, pinch-evoked multiunit discharge rates did not vary between cohorts, although both SCI cohorts had twice as many pinch-responsive electrodes as the neurologically intact cohort. The percentage of electrodes modulated during ISMS did not differ between cohorts, although excitatory actions were preferential in the SCI cohorts. After ISMS, all cohorts exhibited ≥2X more electrodes with altered pinch responsiveness than during ISMS, with depressive actions predominant in the noninjured cohort.

Conclusion: Doubling of the number of electrodes with altered pinch responsiveness after ISMS suggests that ISMS causes a lasting increase in the spatial spread of evoked sensory activity. That this change favored inhibition in 1 cohort is consistent with the possibility of ventral ISMS promoting broad inhibitory control of nociceptive activity.

Keywords: Intraspinal microstimulation; Neuromodulation; Neurorehabilitation; Spinal cord injury; Spinal cord injury–related neuropathic pain.

Grants and funding

R01 NS111234/NS/NINDS NIH HHS/United States