Prostaglandin E2 (PGE2) is a lipid mediator which plays a role in the generation of inflammatory and neuropathic pain. In the peripheral nervous system, PGE2 sensitizes nociceptive afferent neurons through E-prostanoid (EP) receptors. In the central nervous system, PGE2 modulates pain sensitivity and contributes to the development of neuropathic pain. However, the distribution of PGE2 and EP receptors in the spinal cord remains unclear. In the present study, we examined the expression of PGE2 synthases (microsomal PGE synthase [mPGES]-1, mPGES-2, and cytosolic PGE synthase [cPGES]) and EP receptors (EP1-4) in a rat model of neuropathic pain.

We identified that mPGES-1 mRNA was upregulated in spinal endothelial cells after nerve injury and exhibited co-localization with cyclooxygenase-2 (COX-2). We detected that mPGES-2 mRNA and cPGES mRNA were expressed in spinal neurons and noted that their expression level was not affected by nerve injury. With respect to EP receptors, EP2 mRNA and EP4 mRNA were expressed in spinal neurons in the dorsal horn. EP3 mRNA was expressed in motor neurons, whereas EP1 mRNA was not detected in the spinal cord. Intrathecal injection of tumor necrosis factor alpha (TNFα) upregulated mPGES-1 mRNA in blood vessels in the spinal cord. Intrathecal injection of a TNFα-neutralizing antibody partially inhibited the upregulation of mPGES-1 mRNA after nerve injury.

These results indicate that PGE2 is synthesized by COX-2/mPGES-1 in spinal endothelial cells after nerve injury. These results suggest that in neuropathic pain condition, endothelial cell-derived PGE2 may act on EP2 and EP4 receptors on spinal neurons and modulate pain sensitivity.

前列腺素 E2 (PGE2) 是一种脂质介质，在炎症和神经性疼痛的产生中起作用。在外周神经系统中，PGE2 通过 E-前列腺素 (EP) 受体使伤害性传入神经元敏感。在中枢神经系统中，PGE2 调节疼痛敏感性并促进神经性疼痛的发展。然而，PGE2 和 EP 受体在脊髓中的分布仍不清楚。在本研究中，我们检查了 PGE2 合酶（微粒体 PGE 合酶 [mPGES]-1、mPGES-2 和胞质 PGE 合酶 [cPGES]）和 EP 受体 (EP1-4) 在神经性疼痛大鼠模型中的表达。

我们发现 mPGES-1 mRNA 在神经损伤后脊髓内皮细胞中上调，并表现出与环氧合酶-2 (COX-2) 的共定位。我们检测到 mPGES-2 mRNA 和 cPGES mRNA 在脊髓神经元中表达，并注意到它们的表达水平不受神经损伤的影响。关于EP受体，EP2 mRNA和EP4 mRNA在背角的脊髓神经元中表达。EP3 mRNA 在运动神经元中表达，而在脊髓中未检测到 EP1 mRNA。鞘内注射肿瘤坏死因子α（TNFα）可上调脊髓血管中的 mPGES-1 mRNA。鞘内注射 TNFα 中和抗体可部分抑制神经损伤后 mPGES-1 mRNA 的上调。

这些结果表明 PGE2 在神经损伤后的脊髓内皮细胞中由 COX-2/mPGES-1 合成。这些结果表明，在神经性疼痛状况下，内皮细胞来源的 PGE2 可能作用于脊髓神经元上的 EP2 和 EP4 受体并调节疼痛敏感性。