title: The Analgesic and Anxiolytic Effect of Souvenaid, a Novel Nutraceutical, Is Mediated by Alox15 Activity in the Prefrontal Cortex.
abstract: Pain and anxiety have a complex relationship and pain is known to share neurobiological pathways and neurotransmitters with anxiety. Top-down modulatory pathways of pain have been shown to originate from cortical and subcortical regions, including the dorsolateral prefrontal cortex. In this study, a novel docosahexaenoic acid (DHA)-containing nutraceutical, Souvenaid, was administered to mice with infraorbital nerve ligation-induced neuropathic pain and behavioral responses recorded. Infraorbital nerve ligation resulted in increased face wash strokes of the face upon von Frey hair stimulation, indicating increased nociception. Part of this response involves general pain sensitization that is dependent on the CNS, since increased nociception was also found in the paws during the hot plate test. Mice receiving oral gavage of Souvenaid, a nutraceutical containing DHA; choline; and other cell membrane components, showed significantly reduced pain sensitization. The mechanism of Souvenaid's activity involves supraspinal antinociception, originating in the prefrontal cortex, since inhibition of the DHA-metabolizing enzyme 15-lipoxygenase (Alox15) in the prefrontal cortex attenuated the antinociceptive effect of Souvenaid. Alox15 inhibition also modulated anxiety behavior associated with pain after infraorbital nerve ligation. The effects of Souvenaid components and Alox15 on reducing central sensitization of pain may be due to strengthening of a known supraspinal antinociceptive pathway from the prefrontal cortex to the periaqueductal gray. Together, results indicate the importance of the prefrontal cortex and DHA/Alox15 in central antinociceptive pathways and suggest that Souvenaid may be a novel therapeutic for neuropathic pain.
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore, 119260, Singapore.|Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore, Singapore.
authors.forename: Suku-Maran
authors.initials: SM
authors.lastname: Shalini
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore, Singapore.
authors.forename: Deron R
authors.initials: DR
authors.lastname: Herr
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University Health System, National University of Singapore, Singapore, 119260, Singapore. wei_yi_ong@nuhs.edu.sg.|Neurobiology and Ageing Programme, Life Sciences Institute, National University of Singapore, Singapore, Singapore. wei_yi_ong@nuhs.edu.sg.
authors.forename: Wei-Yi
authors.initials: WY
authors.lastname: Ong
mesh_terms: D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy / Q000378:metabolism; D010147:Pain Measurement; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000700:Analgesics; D014151:Anti-Anxiety Agents; D004281:Docosahexaenoic Acids; C521960:Alox15 protein, mouse; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase
keywords: Anxiety; DHA; Depression; Lipoxins, resolvins, neuroprotectins; Pain; iPLA2