What is the proposed mechanism by which Spinal Cord Stimulation (SCS) operates to treat neuropathic pain, specifically regarding the release of neurotransmitters such as glutamate and Gamma-Aminobutyric Acid (GABA) in the dorsal horn of the spinal cord?

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From the Guidelines

The proposed mechanism by which Spinal Cord Stimulation (SCS) operates to treat neuropathic pain is through increased release of GABA in the dorsal horn of the spinal cord.

Mechanism of Action

SCS works by modulating pain transmission at the spinal level through the placement of electrodes in the epidural space that deliver electrical pulses to the dorsal columns. This stimulation activates inhibitory interneurons in the dorsal horn, which then release the inhibitory neurotransmitter GABA 1.

Key Points

  • The increased GABA release suppresses the hyperexcitability of wide dynamic range (WDR) neurons that typically occurs in neuropathic pain conditions.
  • By enhancing inhibitory neurotransmission, SCS effectively closes the "gate" for pain signals traveling from the periphery to the brain, as described in the Gate Control Theory of pain.
  • This mechanism explains why SCS can provide significant pain relief for patients with conditions like failed back surgery syndrome, complex regional pain syndrome, and other neuropathic pain disorders without requiring continuous medication.

Clinical Evidence

While studies such as those published in the Annals of Oncology 1 and the Journal of the National Comprehensive Cancer Network 1 discuss the use of SCS for refractory pain, the most relevant information regarding the mechanism of action is found in the British Journal of Pharmacology 1.

Conclusion Not Needed, only the above information is required to answer the question.

From the Research

Proposed Mechanism of SCS in Treating Neuropathic Pain

The proposed mechanism by which Spinal Cord Stimulation (SCS) operates to treat neuropathic pain involves several key processes:

  • Inhibition of the ascending nociceptive transmission by the release of analgesic neurotransmitters such as GABA and endocannabinoids at the spinal dorsal horn 2, 3, 4
  • Facilitation of the descending inhibition by release of noradrenalin, dopamine, and serotonin acting on their receptors in the spinal cord 2, 4
  • Activation of a variety of supraspinal brain areas related to pain perception and emotion 4
  • Activation of dorsal column Aβ fibers, resulting in variable effects on sensory and pain thresholds, and measurable alterations in higher order cortical processing 5

Release of Neurotransmitters

The release of specific neurotransmitters plays a crucial role in the mechanism of SCS:

  • Increased release of GABA in the dorsal horn of the spinal cord, which may be linked to a decrease in the release of glutamate and other excitatory amino acids, resulting in a decrease of neuropathic pain 2, 3, 4
  • Release of substance P, serotonin, and noradrenaline in the dorsal horns 2
  • No evidence suggests that SCS operates through increased release of glutamate from primary afferent neurons or WDR cells, or increased release of GABA from primary afferent neurons 2, 3, 5, 6, 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

[Spinal cord stimulation].

Masui. The Japanese journal of anesthesiology, 2009

Research

Spinal Cord Stimulation: Clinical Efficacy and Potential Mechanisms.

Pain practice : the official journal of World Institute of Pain, 2018

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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