Synaptamide Improves Cognitive Functions and Neuronal Plasticity in Neuropathic Pain

Abstract

Neuropathic pain arises from damage or dysfunction of the peripheral or central nervous system and manifests itself in a wide variety of sensory symptoms and cognitive disorders. Many studies demonstrate the role of neuropathic pain-induced neuroinflammation in behavioral disorders. For effective neuropathic pain treatment, an integrative approach is required, which simultaneously affects several links of pathogenesis. One promising candidate for this role is synaptamide (N-docosahexaenoylethanolamine), which is an endogenous metabolite of docosahexaenoic acid. In this study, we investigated the activity of synaptamide on mice behavior and hippocampal plasticity in neuropathic pain induced by spared nerve injury (SNI). We found a beneficial effect of synaptamide on the thermal allodynia and mechanical hyperalgesia dynamics. Synaptamide prevented working and long-term memory impairment. These results are probably based on the supportive effect of synaptamide on SNI-impaired hippocampal plasticity. Nerve ligation caused microglia activation predominantly in the contralateral hippocampus, while synaptamide inhibited this effect. The treatment reversed dendritic tree degeneration, dendritic spines density reduction on CA1-pyramidal neurons, neurogenesis deterioration, and hippocampal long-term potentiation (LTP) impairment. In addition, synaptamide inhibits changes in the glutamatergic receptor expression. Thus, synaptamide has a beneficial effect on hippocampal functioning, including synaptic plasticity and hippocampus-dependent cognitive processes in neuropathic pain.

Activation of Liver X receptors alleviates neuropathic pain-induced cognitive dysfunction by modulating PI3K/AKT-mediated microglia polarization

“…Additionally, we observed an increase in the levels of TNF-α and IL-1β and a decrease in the levels of IL-4 and IL-10 in the hippocampus. These results indicate that neuropathic pain induces neuroin ammation in the hippocampus, which is consistent with previous research [40] , [41] , [6] and supports the neuromediator theory.…”

The genetic structure of pain in depression patients: A genome-wide association study and proteome-wide association study

“…41,42 Because of these biological functions, synaptamide play a role in improving cognitive function and neuronal plasticity in neuropathic pain. 43 What's more, Park et al demonstrated the immunomodulatory effects of ADGRF1 in the brain and in the periphery, and jointly promoted the anti-neuroin ammatory effects of synaptamide in systemic in ammatory conditions. These results suggest that ADGRF1 mediated inhibition of innate immune cell activation may be a novel therapeutic strategy for controlling brain and/or peripheral in ammation and related diseases.…”

Regulatory mechanism of Scutellaria baicalensis Georgi on bone cancer pain based on network pharmacology and experimental verification

“…In addition, studies have found that curcumin can alleviate CCI-induced neuropathic pain in rats by remarkably increasing the number of newborn neurons and improving hippocampal neurogenesis and synaptic plasticity ( Du et al, 2021 ). Synaptoamine treatment ameliorated neuropathic pain in mice by reversing decreased dendritic density, worsening hippocampal neurogenesis, and long-term potentiation damage in ca1 pyramidal neurons ( Tyrtyshnaia et al, 2021 ). In this study, the HT22 hippocampal neuron cell line was selected for exploration, and it was found that baicalein and wogonin could promote the occurrence, angiogenesis and proliferation of HT22 cells to relieve pain.…”