Marine-derived bioactive compounds for neuropathic pain: pharmacology and therapeutic potential

Neuropathic pain, a challenging condition often associated with diabetes, trauma, or chemotherapy, impairs patients' quality of life. Current treatments often provide inconsistent relief and notable adverse effects, highlighting the urgent need for safer and more effective alternatives. This review investigates marine-derived bioactive compounds as potential novel therapies for neuropathic pain management. Marine organisms, including fungi, algae, cone snails, sponges, soft corals, tunicates, and fish, produce a diverse range of secondary metabolites with significant pharmacological properties. These include peptides (e.g., conopeptides, piscidin 1), non-peptides (e.g., guanidinium toxins, astaxanthin, docosahexaenoic acid, fucoidan, apigenin, fumagillin, aaptamine, flexibilide, excavatolide B, capnellenes, austrasulfones, lemnalol), and crude extracts (e.g., Spirulina platensis, Dunaliella salina, Cliothosa aurivilli). These compounds exhibit diverse mechanisms of action, such as modulating ion channels (e.g., transient receptor potential channels, voltage-gated sodium, calcium, and potassium channels, and G protein-coupled inwardly rectifying potassium channels), interacting with cell-surface receptors (e.g., nicotinic acetylcholine, NMDA, kainate, GABA_B​, and neurotensin receptors), inhibiting norepinephrine transporters, reducing oxidative stress, and attenuating neuroinflammation. These effects collectively contribute to alleviating nerve degeneration and symptoms of neuropathic pain, including hyperalgesia, allodynia, and associated psychomotor disturbances. Marine-derived bioactive compounds represent promising alternatives to conventional neuropathic pain treatments, to advance their development and assess their integration into neuropathic pain management strategies.