Regulation of Pain Perception by Microbiota in Parkinson Disease

Abstract

Pain perception involves current stimulation in peripheral nociceptive nerves and the subsequent stimulation of postsynaptic excitatory neurons in the spinal cord.Importantly, in chronic pain, the neural activity of both peripheral nociceptors and postsynaptic neurons in the central nervous system is influenced by several inflammatory mediators produced by the immune system. Growing evidence has indicated that the commensal microbiota plays an active role in regulating pain perception by either acting directly on nociceptors or indirectly through the modulation of the inflammatory activity on immune cells. This symbiotic relationship is mediated by soluble bacterial mediators or intrinsic structural components of bacteria that act on eukaryotic cells, including neurons, microglia, astrocytes, macrophages, T-cells, enterochromaffin cells, and enteric glial cells. The molecular mechanisms involve bacterial molecules that act directly on neurons affecting their excitability, or indirectly on non-neuronal cells inducing changes in the production of pro-inflammatory or anti-inflammatory mediators. Importantly, Parkinson's disease, a neurodegenerative and inflammatory disorder that affect mainly the dopaminergic neurons implicated in the control of voluntary movements, involves not only a motor decline but also non-motor symptomatology, including chronic pain. Of note, several recent studies have shown that Parkinson's disease involves a dysbiosis in the composition of the gut microbiota. In this review, first, we summarize, integrate and classify the molecular mechanisms implicated in the microbiota-mediated regulation of chronic pain. Secondly, we analyze the changes on the commensal microbiota associated to Parkinson's disease and propose how these changes affect the development of chronic pain in this pathology.

Targeting short-chain fatty acids receptors signalling for neurological disorders treatment

“…SCFAs that reach the bloodstream might promote CNS homeostasis by reinforcing blood-brain barrier (BBB) integrity, avoiding neuroinflammation, affecting levels of neurotrophic factors, promoting serotonin biosynthesis, or directly activating the vagal afferent. Of note, in addition to diet and dysbiosis, the plasma concentration of SCFAs might be affected by the renin-angiotensin system [11], and by the energy requirements and lipids metabolism [12]. In this regard, acetate and butyrate might be converted into acetyl coenzyme A and subsequently used as substrate in the tricarboxylic acid cycle or beta-oxidation, while propionate might act as a precursor for gluconeogenesis in the liver [12].…”

“…Of note, in addition to diet and dysbiosis, the plasma concentration of SCFAs might be affected by the renin-angiotensin system [11], and by the energy requirements and lipids metabolism [12]. In this regard, acetate and butyrate might be converted into acetyl coenzyme A and subsequently used as substrate in the tricarboxylic acid cycle or beta-oxidation, while propionate might act as a precursor for gluconeogenesis in the liver [12]. According to the crucial role of SCFAs in CNS homeostasis, altered levels of these metabolites have been associated with many neurological diseases.…”

Pesticides and the Gut Microbiota: Implications for Parkinson’s Disease

“…136−139 In another study, through quantitative RT-PCR analyses of fecal samples from 20 PD patients and 20 healthy persons, it was found that Desulfovibrio bacteria were hosted in the intestinal microbiota of all PD patients, with these bacteria being more abundant in PD patients than in healthy controls. 140 Apart from producing H 2 S, Desulfovibrio bacteria are recognized for their production of magnetite (some strains) and lipopolysaccharide, all these are probable elements adding to the clustering and accumulation of the α-syn protein. 98 5.4. α-Syn Pathology in PD and Its Association with Gut Dysbiosis.…”

“…The presence of Desulfovibrio bacteria links with the seriousness of PD. , Consequently, PD patients may experience excess H 2 S. While H 2 S can be beneficial in small quantities, acting as a gaseous neurotransmitter that regulates various body functions, including those in the GI, neuronal, respiratory, cardiovascular, renal, hepatic, and endocrine systems, elevated H 2 S levels resulting from a bloom in sulfate-reducing bacteria can become harmful . Such elevated H 2 S levels are associated with GI disorders such as ulcerative colitis, irritable bowel syndrome, and Crohn’s disease, all of which are linked to an increased risk of PD. − In another study, through quantitative RT-PCR analyses of fecal samples from 20 PD patients and 20 healthy persons, it was found that Desulfovibrio bacteria were hosted in the intestinal microbiota of all PD patients, with these bacteria being more abundant in PD patients than in healthy controls . Apart from producing H 2 S, Desulfovibrio bacteria are recognized for their production of magnetite (some strains) and lipopolysaccharide, all these are probable elements adding to the clustering and accumulation of the α-syn protein …”