Burst and Tonic Spinal Cord Stimulation Differentially Activate GABAergic Mechanisms to Attenuate Pain in a Rat Model of Cervical Radiculopathy.

Abstract

OBJECTIVE:

Spinal cord stimulation (SCS) is widely used to treat neuropathic pain. Burst SCS, an alternative mode of stimulation, reduces neuropathic pain without paresthesia. However, the effects and mechanisms of burst SCS have not been compared to conventional tonic SCS in controlled investigations. This study compares the attenuation of spinal neuronal activity and tactile allodynia, and the role of γ-aminobutyric acid (GABA) signaling during burst or tonic SCS in a rat model of cervical radiculopathy.

METHODS:

The effects of burst and tonic SCS were compared by recording neuronal firing before and after each mode of stimulation at day 7 following a painful cervical nerve root compression. Neuronal firing was also recorded before and after burst and tonic SCS in the presence of the GABAB receptor antagonist, CGP35348.

RESULTS:

Burst and tonic SCS both reduce neuronal firing. The effect of tonic SCS, but not burst SCS, is blocked by CGP35348. In a separate study, spinal cord stimulators were implanted to deliver burst or tonic SCS beginning on day 4 after painful nerve root compression; allodynia and serum GABA concentration were measured through day 14. Burst and tonic SCS both reduce allodynia. Tonic SCS attenuates injury-induced decreases in serum GABA, but GABA remains decreased from baseline during burst SCS.

CONCLUSION AND SIGNIFICANCE:

Together, these studies suggest that burst SCS does not act via spinal GABAergic mechanisms, despite its attenuation of spinal hyperexcitability and allodynia similar to that of tonic SCS; understanding other potential spinal inhibitory mechanisms may lead to enhanced analgesia during burst stimulation.

• Authors: Nathan D Crosby, Christine L Weisshaar, Jenell R Smith, Martha E Zeeman, Melanie D Goodman-Keiser, Beth A Winkelstein
• Journal: IEEE transactions on bio-medical engineering (IEEE Trans Biomed Eng) Vol. 62 Issue 6 Pg. 1604-13 (Jun 2015) ISSN: 1558-2531 [Electronic] United States
• PMID: 25667344 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• GABA Antagonists
• gamma-Aminobutyric Acid

Topics

• Animals
• Behavior, Animal (physiology)
• GABA Antagonists
• Hyperalgesia
• Male
• Neuralgia (therapy)
• Pain Management (methods)
• Radiculopathy (physiopathology)
• Rats
• Spinal Cord Stimulation
• gamma-Aminobutyric Acid (metabolism)