Invasive spinal cord neuromodulation in the treatment of chronic musculoskeletal pain

Abstract

Neuromodulation for analgesic purposes comprises nonablative strategies that modulate neuronal and glial activity to treat refractory chronic pain. It can be pharmacological (gabapentin, antidepressants, medical cannabis), transcutaneous (acupuncture, transcutaneous electrical nerve stimulation (TENS), blocks), or invasive, with spinal cord stimulation (SCS) standing out. In SCS, epidural electrodes apply pulses to the dorsal cord, blocking spinal nociceptive pathways, activating descending systems, and modulating the sympathetic system, with clinically relevant efficacy in approximately two-thirds of cases. Complications include electrode migration or rupture, cerebrospinal fluid leak, hematomas, and spinal cord injury, especially in previously operated spines. Mechanistically, SCS has evolved from the Gate Control Theory to the concept of “neuromatrix”, involving spinal and suprasegmental circuits; it restores GABAergic inhibition, reduces excitatory mediators (e.g., glutamate), and attenuates central and peripheral sensitization. The main indications cover persistent low back pain, complex regional pain syndrome (CRPS), peripheral vascular disease, diabetic neuropathy, and post-arthroplasty pain, with better outcomes in appendicular pain. Critical parameters include the number of poles, frequency, pulse width, and amplitude. Tonic paresthesia-based waveforms (20–90 Hz) and paresthesiafree modalities (>200 Hz), such as burst, high-frequency, and differential target multiplexing (DTM), can be combined and individualized; evidence suggests benefits of high frequencies and burst stimulation, especially for the affective-emotional components of pain. Dorsal root ganglion (DRG) stimulation offers superior control in CRPS and certain low back pain conditions, acting as a peripheral ionic “filter”. Current trends include closed-loop systems with target “electrical dose”, AI customization, and miniaturized hardware. Although cost and limited knowledge hinder diffusion, neuromodulation is emerging as a scalable, cost-effective therapy for complex musculoskeletal pain.