What are the precise mechanisms of spinal cord stimulation, including descending inhibition, and its impact on lower neural centers, such as the spinal cord, in treating clinical pain syndromes like chronic pain (Complex Regional Pain Syndrome)?

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From the Guidelines

Spinal cord stimulation (SCS) is a highly effective treatment for refractory neuropathic and sympathetically-mediated chronic pain, working through complex neurophysiological mechanisms that modulate pain perception by activating descending inhibitory pathways and releasing inhibitory neurotransmitters. The precise mechanisms involved in SCS include the activation of large-diameter Aβ fibers in the dorsal columns of the spinal cord, which triggers the gate control theory of pain, inhibiting painful signals at the dorsal horn [V, C] 1. The stimulation also activates descending inhibitory pathways from the brain, particularly from the periaqueductal gray (PAG) in the midbrain and the rostral ventromedial medulla (RVM), releasing inhibitory neurotransmitters including serotonin, norepinephrine, and gamma-aminobutyric acid (GABA), which suppress pain transmission at the spinal level. Additionally, SCS reduces the release of excitatory neurotransmitters like glutamate and substance P from primary afferent neurons. The areas of the brain that need to be stimulated for effective pain management include the PAG, thalamus, and anterior cingulate cortex. For deep brain stimulation (DBS), targeting these areas can effectively treat intractable neuropathic pain syndromes, such as complex regional pain syndrome (CRPS), by interrupting abnormal neural circuits involved in chronic pain maintenance and restoring normal inhibitory control over pain processing 1. Some key points to consider when using SCS or DBS for pain management include:

  • The importance of proper patient selection, with truly refractory neuropathic pain and failed conservative approaches
  • The need for careful consideration of the risks and benefits of these invasive procedures
  • The potential for significant opioid dose reduction after successful pain intervention
  • The importance of technical expertise and proper patient care to minimize complications and optimize outcomes. Overall, SCS and DBS are valuable tools in the management of refractory chronic pain, offering new hope for patients who have failed conventional treatments.

From the Research

Mechanisms of Spinal Cord Stimulation

The mechanisms involved in spinal cord stimulation (SCS) include:

  • Inhibition of the ascending nociceptive transmission by the release of analgesic neurotransmitters such as GABA and endocannabinoids at the spinal dorsal horn 2
  • Facilitation of the descending inhibition by release of noradrenalin, dopamine, and serotonin acting on their receptors in the spinal cord 2
  • Activation of a variety of supraspinal brain areas related to pain perception and emotion 2

Areas of the Brain Involved

The areas of the brain that need to be stimulated to achieve pain relief through SCS include:

  • The dorsal columns of the spinal cord, which are stimulated to achieve paresthesia covering the area of pain 3
  • The periaqueductal gray matter (PAG) and the nucleus raphe magnus and adjacent structures of the rostral ventromedial medulla (RVM), which constitute the "efferent channel" of a pain-control system that "descends" from the brain onto the spinal cord 4

Neurotransmitter Systems Involved

The neurotransmitter systems involved in the effect of SCS include:

  • GABA, which is released in the dorsal horns and may be linked to a decrease in the release of glutamate and other excitatory amino acids, resulting in a decrease of neuropathic pain 3
  • Noradrenalin, dopamine, and serotonin, which are released in the spinal cord and act on their receptors to facilitate descending inhibition 2
  • Endocannabinoids, which are released in the spinal dorsal horn and contribute to the analgesic effect of SCS 2

Impact on Lower Neural Centers

The impact of SCS on lower neural centers, such as the spinal cord, includes:

  • Inhibition of dorsal horn neuronal activity caused by peripheral noxious stimuli 5
  • Suppressive effect on tactile allodynia 5
  • Increased dorsal horn inhibitory action of GABA 5

Clinical Pain Syndromes

SCS is effective in treating several clinical pain syndromes, including:

  • Complex Regional Pain Syndrome (CRPS) 2, 3, 5
  • Failed Back Surgery Syndrome (FBSS) 2, 3, 5
  • Peripheral neuropathic pain 2, 3, 5
  • Refractory angina 3
  • Spinal cord stenosis 3
  • Low back pain with radiculopathy 5

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

Descending control of persistent pain: inhibitory or facilitatory?

Brain research. Brain research reviews, 2004

Research

Spinal cord stimulation.

Pain physician, 2002

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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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