Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México, México.
Departamento de Enfermería y Obstetricia, División de Ciencias de la Vida, Campus Irapuato-Salamanca, Universidad de Guanajuato, Irapuato, Guanajuato, México.
J Pharm Pharmacol. 2023 Sep 1;75(9):1154-1162. doi: 10.1093/jpp/rgad004.
The antinociceptive pharmacological interaction between N-palmitoylethanolamide (PEA) and morphine (MOR), as well as gabapentin (GBP), was investigated to obtain synergistic antinociception at doses where side effects were minimal. In addition, the possible antinociceptive mechanism of PEA + MOR or PEA + GBP combinations was explored.
Individual dose-response curves (DRCs) of PEA, MOR and GBP were evaluated in female mice in which intraplantar nociception was induced with 2% formalin. Isobolographic method was used to detect the pharmacological interaction in the combination of PEA + MOR or PEA + GBP.
The ED50 was calculated from the DRC; the order of potency was MOR > PEA > GBP. The isobolographic analysis was obtained at a 1:1 ratio to determine the pharmacological interaction. The experimental values of flinching (PEA + MOR, Zexp = 2.72 ± 0.2 μg/paw and PEA + GBP Zexp = 2.77 ± 0.19 μg/paw) were significantly lower than those calculated theoretically (PEA + MOR Zadd = 7.78 ± 1.07 and PEA + GBP Zadd = 24.05 ± 1.91 μg/paw), resulting in synergistic antinociception. Pretreatment with GW6471 and naloxone demonstrated that peroxisome proliferator-activated receptor alpha (PPARα) and opioid receptors are involved in both interactions.
These results suggest that MOR and GBP synergistically enhance PEA-induced antinociception through PPARα and opioid receptor mechanisms. Furthermore, the results suggest that combinations containing PEA with MOR or GBP could be of interest in aiding the treatment of inflammatory pain.
研究 N-棕榈酰乙醇酰胺（PEA）与吗啡（MOR）以及加巴喷丁（GBP）的抗伤害作用的药物相互作用，以获得在副作用最小的剂量下产生协同镇痛作用。此外，还探索了 PEA+MOR 或 PEA+GBP 组合的可能镇痛机制。
在 2%甲醛诱导足底伤害感受的雌性小鼠中，评估 PEA、MOR 和 GBP 的个体剂量反应曲线（DRC）。采用等辐射分析法检测 PEA+MOR 或 PEA+GBP 组合的药物相互作用。
从 DRC 计算 ED50；效价顺序为 MOR＞PEA＞GBP。等辐射分析在 1:1 比例下获得，以确定药物相互作用。缩腿（PEA+MOR，Zexp=2.72±0.2μg/爪和 PEA+GBP Zexp=2.77±0.19μg/爪）的实验值明显低于理论计算值（PEA+MOR Zadd=7.78±1.07 和 PEA+GBP Zadd=24.05±1.91μg/爪），导致协同镇痛作用。GW6471 和纳洛酮预处理表明过氧化物酶体增殖物激活受体α（PPARα）和阿片受体参与了这两种相互作用。
这些结果表明，MOR 和 GBP 通过 PPARα 和阿片受体机制协同增强 PEA 诱导的镇痛作用。此外，这些结果表明，含有 PEA 与 MOR 或 GBP 的组合可能有助于治疗炎症性疼痛。
