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Burst and Tonic Spinal Cord Stimulation Both Activate Spinal GABAergic Mechanisms to Attenuate Pain in a Rat Model of Chronic Neuropathic Pain
- Source :
- Pain Practice, Pain Practice, 20(1), 75-87. Wiley
- Publication Year :
- 2020
-
Abstract
- Background Experimental and clinical studies have shown that tonic spinal cord stimulation (SCS) releases gamma-aminobutyric acid (GABA) in the spinal dorsal horn. Recently, it was suggested that burst SCS does not act via spinal GABAergic mechanisms. Therefore, we studied spinal GABA release during burst and tonic SCS, both anatomically and pharmacologically, in a well-established chronic neuropathic pain model. Methods Animals underwent partial sciatic nerve ligation (PSNL). Quantitative immunohistochemical (IHC) analysis of intracellular GABA levels in the lumbar L4 to L6 dorsal spinal cord was performed after 60 minutes of burst, tonic, or sham SCS in rats that had undergone PSNL (n = 16). In a second pharmacological experiment, the effects of intrathecal administration of the GABA(A) antagonist bicuculline (5 mu g) and the GABA(B) antagonist phaclofen (5 mu g) were assessed. Paw withdrawal thresholds to von Frey filaments of rats that had undergone PSNL (n = 20) were tested during 60 minutes of burst and tonic SCS 30 minutes after intrathecal administration of the drugs. Results Quantitative IHC analysis of GABA immunoreactivity in spinal dorsal horn sections of animals that had received burst SCS (n = 5) showed significantly lower intracellular GABA levels when compared to sham SCS sections (n = 4; P = 0.0201) and tonic SCS sections (n = 7; P = 0.0077). Intrathecal application of the GABA(A) antagonist bicuculline (5 mu g; n = 10) or the GABA(B) antagonist phaclofen (5 mu g; n = 10) resulted in ablation of the analgesic effect for both burst SCS and tonic SCS. Conclusions In conclusion, our anatomical and pharmacological data demonstrate that, in this well-established chronic neuropathic animal model, the analgesic effects of both burst SCS and tonic SCS are mediated via spinal GABAergic mechanisms.
- Subjects :
- Male
TACTILE ALLODYNIA
GABAA/B receptor antagonist
Pharmacology
Tonic (physiology)
Rats, Sprague-Dawley
chemistry.chemical_compound
0302 clinical medicine
030202 anesthesiology
mechanical hypersensitivity
Breceptor antagonist
gamma‐aminobutyric acid
HYPERSENSITIVITY
Spinal Cord Stimulation
integumentary system
GABAA
Sciatic Nerve
burst spinal cord stimulation
medicine.anatomical_structure
ANIMAL-MODELS
Neuropathic pain
GABAergic
DESIGN ELIMINATING CONFUSION
Original Article
Sciatic nerve
tissues
DORSAL-HORN
medicine.drug
gamma-aminobutyric acid
FREQUENCY
gamma-Aminobutyric acid
03 medical and health sciences
Phaclofen
TOUCH-EVOKED ALLODYNIA
medicine
Animals
peripheral nerve injury
Ligation
GAMMA-AMINOBUTYRIC-ACID
business.industry
Original Articles
Bicuculline
Spinal cord
Rats
Disease Models, Animal
Anesthesiology and Pain Medicine
nervous system
chemistry
FUNDAMENTAL DIFFERENCES
Neuralgia
business
030217 neurology & neurosurgery
PERIPHERAL NEUROPATHY
Subjects
Details
- Language :
- English
- ISSN :
- 15307085
- Volume :
- 20
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Pain Practice
- Accession number :
- edsair.doi.dedup.....89def9f26ee6241a1dbb919639abe502