Prostaglandin E₂ and 6‐keto‐prostaglandin F_1α production is elevated following traumatic injury to sciatic nerve†

Abstract

Sciatic nerve explants cultured either alone or in the presence of peritoneal macrophages were used to study prostaglandin E(2) (PGE(2)) and 6-keto-PGF(1alpha) production following traumatic peripheral nerve injury. Although barely detectable at early time points (1-3 h in vitro), the production of PGE(2) and 6-keto-PGF(1alpha) by sciatic nerve explants increased significantly after 18 h and remained elevated for up to 96 h. The cyclooxygenase-2 (COX-2) selective inhibitor, NS-398, inhibited PGE(2) and 6-keto-PGF(1alpha) production by injured sciatic nerve in a dose-dependent manner. Consistent with the observed effect of NS-398, peripheral nerve explants, as well as Schwann cells and perineural fibroblasts cultured from neonatal sciatic nerve, each contained COX-2 immunoreactivity after 24 h in vitro. Both Schwann cells and perineural fibroblasts produced significant amounts of PGE(2) and 6-keto-PGF(1alpha); but only in the presence of arachidonic acid. As observed for injured sciatic nerve, the production of PGE(2) and 6-keto-PGF(1alpha) by primary Schwann cells and perineural fibroblasts was completely inhibited by NS-398. Compared to macrophages cultured alone, macrophages cultured in the presence of sciatic nerve explants produced large amounts of PGE(2), whereas the level of 6-keto-PGF(1alpha) was unchanged. In contrast, macrophages treated with adult sciatic nerve homogenate did not produce significant amounts of either PGE(2) or 6-keto-PGF(1alpha) during the entire course of treatment. We conclude that injured sciatic nerves produce PGE(2) and 6-keto-PGF(1alpha) by a mechanism involving COX-2 activity and that macrophages produce large amounts of PGE(2) in response to soluble factors produced by injured nerve but not during the phagocytosis of peripheral nerve debris.

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

“…In cultured sciatic nerve explants modeling injured nerves, COX-2-dependent production of PGE 2 and PGI 2 increased after 18 h and remained elevated for up to 4 days, while cultured macrophages produced large amounts of PGE 2 and PGI 2 in response to soluble factors eluted from the injured nerve explant (516). In mice with streptozotocin-induced diabetes, the COX-2-selective inhibitor meloxicam reduced mechanical allodynia upon either systemic or perineural (i.e., around the sciatic nerve) but not intrathecal administration, suggesting a contribution of peripheral, COX-2-derived prostanoids to allodynia (363).…”

Molecular Inflammatory Mediators in Peripheral Nerve Degeneration and Regeneration

“…A role for COX-1 expression in microglia and macrophages in tissue remodeling dur-ing WD in the spinal cord has also been proposed [118] . COX-2 production of PGE 2 has been shown to be increased in SCs and macrophages after nerve injury [119] . Another study described how NGF can stimulate COX-dependent production of PGE 2 in inflammatory cells, possibly regulating the inflammatory response and neuronal degeneration after injuries that induce NGF production [120] .…”

Schwann Cell-Derived Factors Modulate Synaptic Activities at Developing Neuromuscular Synapses

“…Schwann cells were reported to produce prostaglandins (Constable et al, 1994;Muja and DeVries, 2004), which have small molecular weights and can modulate synaptic transmission (Harish and Poo, 1992). In our preparation, PGE2 (50 M) increased the SSC frequency by 50-to 100-fold (n ϭ 4; data not shown), and this enhancement of spontaneous release was blocked by the addition of EP1 prostanoid receptor antagonist SC-19220 (30 M) (Kennedy et al, 1982;Fujita et al, 1992).…”