title: Release of GABA and activation of GABA(A) in the spinal cord mediates the effects of TENS in rats.
abstract: Transcutaneous electrical nerve stimulation (TENS) is a commonly utilized non-pharmacological, non-invasive treatment for pain. GABA is a neurotransmitter in the dorsal horn of the spinal cord that mediates analgesia locally, and also through activation of supraspinal sites. TENS reduces hyperalgesia through activation of receptor-mediated pathways at the level of the spinal cord, and supraspinally. The current study tested the hypothesis that either high or low frequency TENS applied to the inflamed knee joint increases GABA in the spinal cord dorsal horn and activates GABA receptors spinally. We utilized microdialysis to sample the extracellular fluid before, during and after TENS and analyzed GABA in dialysates with high performance liquid chromatography. We analyzed the extracellular GABA concentrations in animals with and without knee joint inflammation induced by intra-articular injection of kaolin and carrageenan. We further tested if spinal blockade of GABA receptors prevents the antihyperalgesia produced by TENS in rats with joint inflammation. We show that high frequency TENS increases extracellular GABA concentrations in the spinal cord in animals with and without joint inflammation. The increases in GABA do not occur in response to low frequency TENS, and there are no increases in glycine in response to low or high frequency TENS. However, the reduction in primary hyperalgesia by both high and low frequency TENS is prevented by spinal blockade of GABA(A) receptors with bicuculline. Thus, high frequency TENS increases release of GABA in the deep dorsal horn of the spinal cord, and both high and low frequency TENS reduce primary hyperalgesia by activation of GABA(A) receptors spinally.
authors.affiliation: Physical Therapy and Rehabilitation Science Graduate Program, Neuroscience Graduate Program, Pain Research Program, 1-242 MEB, University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Maeda
authors.forename: T L
authors.initials: TL
authors.lastname: Lisi
authors.forename: C G T
authors.initials: CG
authors.lastname: Vance
authors.forename: K A
authors.initials: KA
authors.lastname: Sluka
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002351:Carrageenan; D004307:Dose-Response Relationship, Radiation; D005998:Glycine / Q000378:metabolism; D006930:Hyperalgesia / Q000209:etiology / Q000628:therapy; D007270:Injections, Intra-Articular; D007616:Kaolin; D007718:Knee Injuries / Q000139:chemically induced / Q000150:complications / Q000473:pathology / Q000628:therapy; D008297:Male; D017551:Microdialysis; D010147:Pain Measurement; D017288:Pain Threshold / Q000528:radiation effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism* / Q000528:radiation effects*; D013997:Time Factors; D004561:Transcutaneous Electric Nerve Stimulation / Q000379:methods*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D011963:Receptors, GABA-A; D007616:Kaolin; D005680:gamma-Aminobutyric Acid; D002351:Carrageenan; D005998:Glycine