Marine Toxins and Nociception: Potential Therapeutic Use in the Treatment of Visceral Pain Associated with Gastrointestinal Disorders

Abstract

Visceral pain, of which the pathogenic basis is currently largely unknown, is a hallmark symptom of both functional disorders, such as irritable bowel syndrome, and inflammatory bowel disease. Intrinsic sensory neurons in the enteric nervous system and afferent sensory neurons of the dorsal root ganglia, connecting with the central nervous system, represent the primary neuronal pathways transducing gut visceral pain. Current pharmacological therapies have several limitations, owing to their partial efficacy and the generation of severe adverse effects. Numerous cellular targets of visceral nociception have been recognized, including, among others, channels (i.e., voltage-gated sodium channels, VGSCs, voltage-gated calcium channels, VGCCs, Transient Receptor Potential, TRP, and Acid-sensing ion channels, ASICs) and neurotransmitter pathways (i.e., GABAergic pathways), which represent attractive targets for the discovery of novel drugs. Natural biologically active compounds, such as marine toxins, able to bind with high affinity and selectivity to different visceral pain molecular mediators, may represent a useful tool (1) to improve our knowledge of the physiological and pathological relevance of each nociceptive target, and (2) to discover therapeutically valuable molecules. In this review we report the most recent literature describing the effects of marine toxin on gastrointestinal visceral pain pathways and the possible clinical implications in the treatment of chronic pain associated with gut diseases.

Medicine in motion: Opportunities, challenges and data analytics-based solutions for traditional medicine integration into western medical practice

“…This has been demonstrated for example using the archetypal TRPV1 ligand capsaicin as a pain therapy and we have demonstrated it for cannabinoid and terpene ligands for TRPV1 ( Backonja et al, 2010 ; De Caro et al, 2019 ; Jansen et al, 2019 ; Starkus et al, 2019 ; Talavera et al, 2020 ). Nocioceptive TRPs have an extensive pharmacopeia of plant secondary metabolites ( Baj et al, 2019 ). Thus, agonist ligands for TRPVs that are found in plant secondary metabolomes can act as analgesics.…”

Tryptophan Metabolites Along the Microbiota-Gut-Brain Axis: An Interkingdom Communication System Influencing the Gut in Health and Disease

“…98 Visceral pain as a microbiota-gut-brain axis dysfunction in IBS. In IBS patients, alterations of the microbial flora may underlie visceral hyperalgesia, defined as a poorly localized and diffuse chronic abdominal pain 221,266 (Table 1). In particular, changes in the amounts of specific phyla, such as Proteobacteria, were correlated with the scores of visceral pain in IBS patients.…”

“…221 In particular, NMDA receptors located on complex neuronal networks in the spinal cord may promote the amplification of nociceptive signals and the 'wind-up' of central responses to nociceptive stimuli. 221,266 Several studies suggest that kynurenic acid and its synthetic analogues may offer novel therapeutic options for the treatment of neuropathic pain syndromes devoid of significant adverse effects. [289][290][291] Tryptophan metabolites and IBS-associated anxiety and depression.…”

Dinoflagellates Important Marine Producers of Natural Bio-Compounds with High Biotechnological and Pharmacological Potential

“…Scientists have recognized some receptor sites of the perception of painful sensations on which new biologically active natural compounds could more effectively act. Marine toxins represent, in fact, high affinity and selectivity to different molecular mediators of visceral pain, acting in particular on ion channels and receptors involved in pain generation [43]. Their use is very useful for studying the properties of ionic channels and receptors involved in pain perception, improving knowledge of their pathophysiological properties.…”