Chronic
neuropathic pain is a condition that causes both sensory disturbances and a variety of functional disorders, indicating the involvement of various brain structures in
pain pathogenesis. One of the factors underlying chronic
neuropathic pain is
neuroinflammation, which is accompanied by microglial activation and pro-inflammatory factor release.
N-docosahexaenoylethanolamine (
DHEA,
synaptamide) is an
endocannabinoid-like metabolite synthesized endogenously from
docosahexaenoic acid.
Synaptamide exhibits anti-inflammatory activity and improves neurite outgrowth, neurogenesis, and synaptogenesis within the hippocampus. This study aims to evaluate the effects of
synaptamide obtained by the chemical modification of DHA, extracted from the Far Eastern raw material Berryteuthis magister on neuroinflammatory response and hippocampal neurogenesis changes during
neuropathic pain. The study of microglial
protein and
cytokine concentrations was performed using immunohistochemistry and ELISA. The brain
lipid analysis was performed using the liquid chromatography-mass spectrometry technique. Behavioral experiments showed that
synaptamide prevented
neuropathic pain-associated sensory and behavioral changes, such as
thermal allodynia, impaired locomotor activity, working and long-term memory, and increased anxiety.
Synaptamide attenuated microglial activation, release of proinflammatory
cytokines, and decrease in hippocampal neurogenesis.
Lipid analysis revealed changes in the brain
N-acylethanolamines composition and
plasmalogen concentration after
synaptamide administration. In conclusion, we show here that
synaptamide may have potential for use in preventing or treating neuropathic cognitive
pain and emotional effects.