Interleukin-1β Plays Key Roles in LPA-Induced Amplification of LPA Production in Neuropathic Pain Model

Abstract

Lysophosphatidic acid (LPA) is a bioactive lipid mediator that exerts a wide range of biological actions. In recent decades, LPA has been demonstrated as an important initiator of neuropathic pain based on the mechanisms of LPA-induced feed-forward LPA amplification. In this study, we examined the possible involvement of interleukin (IL)-1β in such LPA production. Intrathecal (i.t.) LPA injection rapidly increased the expression of IL-1β mRNA in the spinal dorsal horn as early as 0.5 h after injection, and the level reached peak at 2 h. Through a developed quantitative mass spectrometry for detecting LPA species, the elevated levels of 18:1, 16:0, and 18:0 LPA in the spinal dorsal horn were observed at 3 h after 18:1 LPA injection and this elevation was completely blocked by the pretreatment of IL-1β-neutralizing antibody. Moreover, enzyme assay experiments showed that LPA (i.t.) significantly activated calcium-independent phospholipase A2 (iPLA2) and cytosolic phospholipase A2 (cPLA2) in the spinal dorsal horn at 1 and 2 h, respectively, and these biochemical changes were also significantly inhibited by IL-1β-neutralizing antibody. Similarly, IL-1β-neutralizing antibody reversed LPA-induced neuropathic pain-like behavior. These findings suggest that the early release of IL-1β is involved in LPA-induced amplification of LPA production, which underlies the initial mechanisms of LPA-induced neuropathic pain.

P2Y12 receptor upregulation in satellite glial cells is involved in neuropathic pain induced by HIV glycoprotein 120 and 2′,3′-dideoxycytidine

“…Pro-inflammatory cytokines can activate SGCs, as a feedback, SGC activation may cause more release of pro-inflammatory cytokines, that will increase abnormal neuronal excitability and contribute to neuropathic pain. TNF-α and IL-1β play important roles in neuropathic pain [33,34]. Our results showed that expression levels of 12 receptor mRNA and protein were enhanced in gp120+ ddC-treated rats and were accompanied by upregulated IL-1β protein.…”

Resolvin D1 Inhibits Mechanical Hypersensitivity in Sciatica by Modulating the Expression of Nuclear Factor-κB, Phospho-extracellular Signal–regulated Kinase, and Pro- and Antiinflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion

“…40 Gene therapy of silencing TNF-α expression relieved neuropathic pain in L5 spinal nerve transaction model rats. 42,43 IL-1β knockout or IL-1β antibody treatment 43,44 showed significant alleviation of neuropathic pain, and injection of recombinant IL-1β induced mechanical pain. 42,43 IL-1β knockout or IL-1β antibody treatment 43,44 showed significant alleviation of neuropathic pain, and injection of recombinant IL-1β induced mechanical pain.…”

Lysophosphatidic Acid and its Receptors LPA1 and LPA3 Mediate Paclitaxel-Induced Neuropathic Pain in Mice

“…Alternatively, LPA 1 and LPA 3 receptors are expressed in microglia [ 34 , 35 ], indicating microglial LPA 1 and LPA 3 receptors might induce the release of biological factors that activate iPLA 2 and cPLA 2 to cause LPA production. One such candidate is interleukin-1β, which mediates LPA-induced LPA production via activations of iPLA 2 and cPLA 2 [ 36 ].…”