Nerves can be activating or deliver inhibitory signals. The ones that excite often produce a molecule called gluatamate and the inhibitory one is called GABA. When you get spasticity, it can result from a change in the balance excitation and inhibition. You can try to block the excitation or augment the inhibition. For example which is what baclofen does. It increases the inhibition. You can image the presence of glutamate and GABA using magnetic resonance spectroscopy. In this study they found inbalances in the glutamate and GABA.
What can we do about this inbalance we can block the excitation but this can be sedating or one can augment the inhibition but this is also sedating. Also if you really block the excitatory glutamate receptors and you would do doolally. There are few thrapeutic drugs that hit this target and are very week inhibitors. If you are interested you can have a look at Memantine for Multiple Sclerosis: A Systematic Review and Meta-Analysis of Randomized Trials.Turalde CWR, Espiritu AI, Anlacan VMM.Front Neurol. 2021 Feb 15;11:574748
These glutamate work by allowing movement of calcium ions into the cell and as such they are called ionotrophic and the calcium ions help create the electrical activity that gets the nerves firing..
Altered in vivo brain GABA and glutamate levels are associated with multiple sclerosis central fatigue.Arm J, Oeltzschner G, Al-Iedani O, Lea R, Lechner-Scott J, Ramadan S.Eur J Radiol. 2021 Feb 24;137:109610. doi: 10.1016/j.ejrad.2021.109610. Online ahead of print.
Purpose: Fatigue is a common symptom in patients with multiple sclerosis (MS) with unknown pathophysiology. Dysfunction of the GABAergic/glutamatergic pathways involving inhibitory and excitatory neurotransmitters such as γ-aminobutyric acid (GABA) and glutamine + glutamate pool (Glx) have been implicated in several neurological disorders. This study is aimed to evaluate the potential role of GABA and Glx in the origin of central fatigue in relapse remitting MS (RRMS) patients.
Methods: 24 RRMS patients and 16 age- and sex-matched healthy controls (HC) were scanned using Mescher-Garwood point resolved spectroscopy (MEGA-PRESS) with a 3 T system to quantify GABA+ and Glx from prefrontal (PFC) and sensorimotor (SMC) cortices. Self-reported fatigue status was measured on all participants using the Modified Fatigue Impact Scale (MFIS).
Results: RRMS patients had higher fatigue scores relative to HC (p ≤ 0.05). Compared to HC, Glx levels in RRMS patients were significantly decreased in SMC (p = 0.04). Significant correlations were found between fatigue scores and GABA+ (r = -0.531, p = 0.008) and Glx (r = 0.511, p = 0.018) in PFC. Physical fatigue was negatively correlated with GABA+ in SMC and PFC (r = -0.428 and -0.472 respectively, p ≤ 0.04) and positively with PFC Glx (r = 0.480, p = 0.028).
Conclusion: The associations between fatigue and GABA + and Glx suggest that there might be dysregulation of GABAergic/glutamatergic neurotransmission in the pathophysiological mechanism of central fatigue in MS.
So you may be interested the next paper. As not all glutamate receptors involve movement of ions there others that are called metabotropic gluatmate receptors there are alot of them. One is involved in have the natural cannabis work. Too much glutamate signalling may cause nerve damage. So this paper points out one possible new target
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system with continuous neuronal loss. Treatment of clinical progression remains challenging due to lack of insights into inflammation-induced neurodegenerative pathways. Here, we show that an imbalance in the neuronal receptor interactome is driving glutamate excitotoxicity in neurons of MS patients and identify the MS risk–associated metabotropic glutamate receptor 8 (GRM8) as a decisive modulator. Mechanistically, GRM8 activation counteracted neuronal cAMP accumulation, thereby directly desensitizing the inositol 1,4,5-trisphosphate receptor (IP3R). This profoundly limited glutamate-induced calcium release from the endoplasmic reticulum and subsequent cell death. Notably, we found Grm8-deficient neurons to be more prone to glutamate excitotoxicity, whereas pharmacological activation of GRM8 augmented neuroprotection in mouse and human neurons as well as in a preclinical mouse model of MS. Thus, we demonstrate that GRM8 conveys neuronal resilience to CNS inflammation and is a promising neuroprotective target with broad therapeutic implicatio