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The Pharmacology of Central Sensitization
Published in Robert M. Bennett, The Clinical Neurobiology of Fibromyalgia and Myofascial Pain, 2020
Rie Suzuki, Anthony H. Dickenson
Gamma-aminobutyric acid [GABA] forms the major inhibitory transmitter system within the spinal cord and appears to exert tonic inhibitory controls on excitatory transmission. Various receptors for GABA have been identified and these have been classified into two subtypes, the GABAa receptor and GABAB receptor.
Neurotransmitters in Characean Electrical Signaling
Published in Akula Ramakrishna, Victoria V. Roshchina, Neurotransmitters in Plants, 2018
Vilma Kisnieriene, Indre Lapeikaite, Vilmantas Pupkis
GABA is a major inhibitory neurotransmitter whose effect on Characean cells could be investigated using voltage clamp. GABA in CNS acts as a signal by regulating ion flow across cell membranes via two classes of receptors, the GABAA and GABAB (Bouché and Fromm 2004). Ionotropic GABAA receptors consist of multiple subunits that can assemble into a functional homomeric or heteromeric channel. GABA exerts its inhibitory effect in mature brain neurons by the activation of Cl− currents through GABAA receptor channels. This tends to hyperpolarize the membrane potential and inhibits excitability. In addition to acting on the ionotropic GABAA receptor, GABA is also an endogenous agonist of the GABAB receptor, which is a member of the large metabotropic G-protein coupled receptor superfamily (Lucas 2011).
γ-hydroxybutyrate (GHB) and γ-butyrolactone (GBL)
Published in Linda M. Castell, Samantha J. Stear (Nottingham), Louise M. Burke, Nutritional Supplements in Sport, Exercise and Health, 2015
Alex D. Popple, Michael J. Naylor
γ-hydroxybutyrate (GHB) is a short chain 4-carbon fatty acid found in the brain, mainly in the hypothalamus and basal ganglia, in the form of γ-hydroxybutyric acid. GHB has several precursors including γ-butyrolactone (GBL), that are metabolised into GHB upon ingestion through various pathways. Concurrently, GHB is transformed into the inhibitory neurotransmitter γ-aminobutyric acid (GABA), with preference for the GABAb receptor.
Restoration of rostral cerebrospinal fluid flow to solve treatment failure caused by obstruction in long-term intrathecal baclofen administration
Published in The Journal of Spinal Cord Medicine, 2021
Elmar M. Delhaas, Biswadjiet S. Harhangi, Pieter J. van Doormaal, Wouter Dinkelaar, Ad C.G.M. van Es, Danielle M.E. van Assema, Sander P.G. Frankema, Aad van der Lugt, Frank J.P.M. Huygen
Following a spinal cord injury (SCI), 62% to 88% of the patients develop spasticity.1–4 Nonetheless, the resulting muscle tone might have advantages, such as advantages during transfers or as a clinical indicator of noxious stimuli.5 In generalized spasticity, the GABA-B receptor agonist baclofen is the most frequently used drug. Since 1984, intrathecal baclofen (ITB) has become an often used therapy in intractable cases.6 A rostral cerebrospinal fluid (CSF) flow obstruction is a rare cause of long-term ITB failure. In this paper, we describe five adult SCI patients with an ITB failure caused by a rostral CSF flow obstruction. After CSF flow restoration either by microsurgical adhesiolysis, intradural bypass,7,8 or percutaneous fenestration, we evaluated the ITB treatment effect. CSF flow restoration was attempted based on the following observations: a successful clinical treatment with an intradural shunt in a patient with a CSF flow obstruction (not published); cerebral cistern visualization with 111Indium-diethylene-triamine-penta-acetic acid scintigraphy (111In-DTPA) in normal cases; the lack of treatment effect when the catheter tip was placed above an obstruction; and cerebral symptomatology, which occurred upon an ITB overdose. Based on these observations, we hypothesized that besides the regional effect of ITB, rostral CSF flow is also needed for effective ITB treatment, and that the restoration of rostral CSF flow in obstructions could be a useful therapy in the case of ITB failure.
Mechanisms and mode of action of spinal cord stimulation in chronic neuropathic pain
Published in Postgraduate Medicine, 2020
Lonne Heijmans, Elbert A. Joosten
Preclinical studies have established the involvement of the neurotransmitter GABA and the inhibitory GABAergic interneurons in the mechanism underlying tonic SCS mediated analgesia. Extracellular GABA concentrations in the dorsal horn of neuropathic rats were shown to be increased during SCS [4]. Furthermore, Janssen et al. showed reduced intracellular GABA immunoreactivity in the dorsal horn of rats with Partial Sciatic Nerve Ligation (PSNL) after 30 minutes of tonic SCS [5]. From this, it is concluded that tonic SCS induced GABA release into the extracellular space in the spinal dorsal horn and that this is a pivotal mechanism underlying the pain-relieving mechanism of tonic SCS. Intrathecal pharmacological studies have further elucidated and detailed the involvement of this GABAergic mechanism in tonic SCS, demonstrating in particular the GABAB receptor to be very important [6,7]. Importantly these preclinical findings have been translated into the clinic, demonstrating that the synergistic effect of administering a subclinical dose of the GABAB receptor agonist baclofen and tonic SCS turned SCS non-responders into responders [8].
The selective BDNF overexpression in neurons protects neuroglial networks against OGD and glutamate-induced excitotoxicity
Published in International Journal of Neuroscience, 2020
S. G. Gaidin, M. V. Turovskaya, M. S. Gavrish, A. A. Babaev, V. N. Mal’tseva, E. V. Blinova, E. A. Turovsky
GABA(B) receptors are tightly coupled with BDNF release [81,82]. For instance, the enhancement of BDNF release into extracellular space is observed under the activation of GABA(B) receptors. Besides, it is shown that this pathway includes PLC activation, diacylglycerol accumulation, activation of PKC and L-type voltage-gated calcium channels [82]. We have demonstrated that expression of the GABA(B) receptor subunit significantly increased which can be explained by the necessity of release of excessive BDNF concentrations from transduced neurons. Besides, the decrease of expression of PKCa and PKCg isoforms was observed in our experiments. It is known that the activity of protein kinases from cytosolic fraction of hippocampal neurons can be decreased under excessive activation of GABA(B) receptors [83]. Thus, increased Gabbr1 expression in cell cultures with BDNF overexpression can be considered as a positive modulator of BDNF release, contributing to network inhibition.