Repeated spinal cord stimulation decreases the extracellular level of γ-aminobutyric acid in the periaqueductal gray matter of freely moving rats

Most of the previous experimental studies on the antinociceptive effects of electrical spinal cord stimulation (SCS) have focused on short-lasting effects mainly depending on spinal mechanisms. However, patients treated with SCS for chronic pain often report pain relief exceeding the period of stimu...

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Published inBrain research Vol. 699; no. 2; pp. 231 - 241
Main Authors Stiller, Carl-Olav, Linderoth, Bengt, T. O'Connor, William, Franck, Johan, Falkenberg, Torkel, Ungerstedt, Urban, Brodin, Ernst
Format Journal Article
LanguageEnglish
Published London Elsevier B.V 20.11.1995
Amsterdam Elsevier
New York, NY
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Abstract Most of the previous experimental studies on the antinociceptive effects of electrical spinal cord stimulation (SCS) have focused on short-lasting effects mainly depending on spinal mechanisms. However, patients treated with SCS for chronic pain often report pain relief exceeding the period of stimulation for several hours. The long lasting effect of SCS might not only involve spinal, but also supraspinal mechanisms. A supraspinal region of major importance for the coordination of descending pain inhibition is the periaqueductal grey matter (PAG). The aim of the present microdialysis study, performed in awake freely moving rats, was to investigate if repeated SCS (two 30 min periods separated by a 90 min resting period) alters the extracellular neurotransmitter concentrations in the ventrolateral PAG. In a first series of experiments significantly decreased (−30%; P < 0.05; n = 7) γ-aminobutyric acid (GABA) levels were detected immediately after the second SCS session. Neither the concentration of serotonin nor that of substance P-like immunoreactivity (SP-LI) was affected by SCS. The decrease of GABA after two SCS sessions was confirmed in a second series of experiments (−30%; P < 0.05; n = 7). No spontaneous decline of GABA was observed in sham-stimulated animals ( n = 6). The glutamate concentration was also determined in this latter series of experiments and a significant decrease (−23%; P < 0.05; n = 5) was observed after the second SCS session. As GABA-neurons in the PAG exert a tonic depressive effect on the activity in descending pain inhibitory pathways, a decreased extracellular GABA level in this region, as detected following repeated SCS, might indicate an increased pain inhibition.
AbstractList Most of the previous experimental studies on the antinociceptive effects of electrical spinal cord stimulation (SCS) have focused on short-lasting effects mainly depending on spinal mechanisms. However, patients treated with SCS for chronic pain often report pain relief exceeding the period of stimulation for several hours. The long lasting effect of SCS might not only involve spinal, but also supraspinal mechanisms. A supraspinal region of major importance for the coordination of descending pain inhibition is the periaqueductal grey matter (PAG). The aim of the present microdialysis study, performed in awake freely moving rats, was to investigate if repeated SCS (two 30 min periods separated by a 90 min resting period) alters the extracellular neurotransmitter concentrations in the ventrolateral PAG. In a first series of experiments significantly decreased (- 30%; P < 0.05; n = 7) gamma -aminobutyric acid (GABA) levels were detected immediately after the second SCS session. Neither the concentration of serotonin nor that of substance P-like immunoreactivity (SP-LI) was affected by SCS. The decrease of GABA after two SCS sessions was confirmed in a second series of experiments (- 30%; P < 0.05; n = 7). No spontaneous decline of GABA was observed in sham-stimulated animals (n = 6). The glutamate concentration was also determined in this latter series of experiments and a significant decrease (- 23%; P < 0.05; n = 5) was observed after the second SCS session. As GABA-neurons in the PAG exert a tonic depressive effect on the activity in descending pain inhibitory pathways, a decreased extracellular GABA level in this region, as detected following repeated SCS, might indicate an increased pain inhibition.
Most of the previous experimental studies on the antinociceptive effects of electrical spinal cord stimulation (SCS) have focused on short-lasting effects mainly depending on spinal mechanisms. However, patients treated with SCS for chronic pain often report pain relief exceeding the period of stimulation for several hours. The long lasting effect of SCS might not only involve spinal, but also supraspinal mechanisms. A supraspinal region of major importance for the coordination of descending pain inhibition is the periaqueductal grey matter (PAG). The aim of the present microdialysis study, performed in awake freely moving rats, was to investigate if repeated SCS (two 30 min periods separated by a 90 min resting period) alters the extracellular neurotransmitter concentrations in the ventrolateral PAG. In a first series of experiments significantly decreased (−30%; P < 0.05; n = 7) γ-aminobutyric acid (GABA) levels were detected immediately after the second SCS session. Neither the concentration of serotonin nor that of substance P-like immunoreactivity (SP-LI) was affected by SCS. The decrease of GABA after two SCS sessions was confirmed in a second series of experiments (−30%; P < 0.05; n = 7). No spontaneous decline of GABA was observed in sham-stimulated animals ( n = 6). The glutamate concentration was also determined in this latter series of experiments and a significant decrease (−23%; P < 0.05; n = 5) was observed after the second SCS session. As GABA-neurons in the PAG exert a tonic depressive effect on the activity in descending pain inhibitory pathways, a decreased extracellular GABA level in this region, as detected following repeated SCS, might indicate an increased pain inhibition.
Most of the previous experimental studies on the antinociceptive effects of electrical spinal cord stimulation (SCS) have focused on short-lasting effects mainly depending on spinal mechanisms. However, patients treated with SCS for chronic pain often report pain relief exceeding the period of stimulation for several hours. The long lasting effect of SCS might not only involve spinal, but also supraspinal mechanisms. A supraspinal region of major importance for the coordination of descending pain inhibition is the periaqueductal grey matter (PAG). The aim of the present microdialysis study, performed in awake freely moving rats, was to investigate if repeated SCS (two 30 min periods separated by a 90 min resting period) alters the extracellular neurotransmitter concentrations in the ventrolateral PAG. In a first series of experiments significantly decreased (-30%; P &lt; 0.05; n = 7) gamma-aminobutyric acid (GABA) levels were detected immediately after the second SCS session. Neither the concentration of serotonin nor that of substance P-like immunoreactivity (SP-LI) was affected by SCS. The decrease of GABA after two SCS sessions was confirmed in a second series of experiments (-30%; P &lt; 0.05; n = 7). No spontaneous decline of GABA was observed in sham-stimulated animals (n = 6). The glutamate concentration was also determined in this latter series of experiments and a significant decrease (-23%; P &lt; 0.05; n = 5) was observed after the second SCS session. As GABA-neurons in the PAG exert a tonic depressive effect on the activity in descending pain inhibitory pathways, a decreased extracellular GABA level in this region, as detected following repeated SCS, might indicate an increased pain inhibition.
Author Falkenberg, Torkel
Ungerstedt, Urban
T. O'Connor, William
Franck, Johan
Linderoth, Bengt
Brodin, Ernst
Stiller, Carl-Olav
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  fullname: Brodin, Ernst
  organization: Department of Physiology and Pharmacology, Karolinska Institute, S-171 77 Stockholm ,Sweden
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Issue 2
Keywords 5-Hydroxytryptamine
γ-Amino-butyric-acid
Microdialysis
Rat
Periaqueductal gray matter
Substance P
Spinal cord stimulation
Glutamate
Spinal cord
Electrical stimulus
Rodentia
Central nervous system
Vertebrata
Mammalia
Pain
Treatment
Neurotransmitter
GABA
Brain (vertebrata)
Language English
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SSID ssj0003390
Score 1.811588
Snippet Most of the previous experimental studies on the antinociceptive effects of electrical spinal cord stimulation (SCS) have focused on short-lasting effects...
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StartPage 231
SubjectTerms 5-Hydroxytryptamine
Animals
Biological and medical sciences
Calcium - physiology
Central nervous system
Central neurotransmission. Neuromudulation. Pathways and receptors
Electric Stimulation
Fundamental and applied biological sciences. Psychology
gamma-Aminobutyric Acid - metabolism
Glutamate
Glutamic Acid - metabolism
Male
Medicin och hälsovetenskap
Microdialysis
Pain Measurement
Periaqueductal Gray - metabolism
Periaqueductal gray matter
Rat
Rats
Rats, Sprague-Dawley
Serotonin - metabolism
Spinal Cord - physiology
Spinal cord stimulation
Substance P
Vertebrates: nervous system and sense organs
γ-Amino-butyric-acid
Title Repeated spinal cord stimulation decreases the extracellular level of γ-aminobutyric acid in the periaqueductal gray matter of freely moving rats
URI https://dx.doi.org/10.1016/0006-8993(95)00911-9
https://www.ncbi.nlm.nih.gov/pubmed/8616626
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https://search.proquest.com/docview/77849400
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Volume 699
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