Analgesic Activity of Synaptamide in a Rat Sciatic Nerve Chronic Constriction Injury Model.

Abstract

At present, there is a growing interest in the study of the neurotropic activity of polyunsaturated fatty acid ethanolamides (N-acylethanolamines). N-docosahexaenoylethanolamine (DHEA), or synaptamide, an endogenous metabolite of docosahexaenoic acid, is a promising compound with anti-inflammatory activity. The results of this study demonstrate that synaptamide, when administered subcutaneously (4 mg/kg/day, 35 days), promotes a decrease in cold allodynia and mechanical hyperalgesia in a rat sciatic nerve chronic constriction injury (CCI) model. After CCI, synaptamide treatment enhanced the remyelination process in the site of sciatic nerve injury (33.4 ± 1.1% in the CCI+Syn group, compared to 28.4 ± 0.9% in the CCI group). Further, synaptamide suppressed the CCI-induced increase in the activity of microglia (13.1 ± 0.5% in CCI+Syn, compared to 15.3 ± 0.7% in the CCI group) and the number of nitric oxide synthase-positive neurons (58,307 ± 5,206 cells/mm3 in CCI+Syn, compared to 80,288 ± 4,287 cells/mm3 in the CCI group) in the dorsal horns of the spinal cord, and also reduced the concentration of interleukin 1 beta in the spinal cord (169.3 ± 4 pg/mg of protein in CCI+Syn, compared to 236.9 ± 9.3 pg/mg of protein in CCI group) 35 days after surgery. Synaptamide treatment resulted in decrease of reactive astrogliosis in the spinal cord dorsal horns to 20.8 ± 1.3%, which occurred simultaneously with a decrease in the substance P (SP) level (9.8 ± 0.5%) compared to vehicle-treated animals (30.2 ± 2.2% and 13.4 ± 0.9% of astroglia and SP staining area, respectively). In addition, synaptamide increased superoxide dismutase activity up to 68.6 ± 0.8% (control 50.6 ± 0.9%) in astrocyte culture. Thus, synaptamide provides anti-inflammatory and neuroprotective effects in both peripheral and central nervous system after sciatic nerve injury.

• Authors: Anna Starinets, Anna Tyrtyshnaia, Yulia Kipryushina, Igor Manzhulo
• Journal: Cells, tissues, organs (Cells Tissues Organs) Vol. 211 Issue 1 Pg. 73-84 ( 2022) ISSN: 1422-6421 [Electronic] Switzerland
• PMID: 34510045 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 S. Karger AG, Basel.

Chemical References

• Analgesics
• Anti-Inflammatory Agents
• Ethanolamines
• synaptamide

Topics

• Analgesics
• Animals
• Anti-Inflammatory Agents
• Constriction
• Ethanolamines
• Hyperalgesia (drug therapy)
• Rats
• Sciatic Nerve (injuries)
• Spinal Cord