title: Lipoxin A4 attenuates radicular pain possibly by inhibiting spinal ERK, JNK and NF-κB/p65 and cytokine signals, but not p38, in a rat model of non-compressive lumbar disc herniation.
abstract: Inflammatory response induced by protrused nucleus pulposus (NP) has been shown to play a crucial role in the process of radicular pain. Lipoxins represent a unique class of lipid mediators that have anti-inflammatory and pro-resolving action. The present study was undertaken to investigate if intrathecal lipoxin A4 (LXA4) could alleviate mechanical allodynia in the rat models of application of NP to the L5 dorsal root ganglion (DRG). Non-compressive models of application of NP to L5 DRG were established and intrathecal catheterization for drug administration was performed in rats. Daily intrathecal injection of vehicle or LXA4 (10ng or 100ng) was performed for three successive days post-operation. Mechanical thresholds were tested and the ipsilateral lumbar (L4-L6) segment of spinal dorsal horns were removed for the determination of tumor necrosis factor-α (TNF-α), IL-1β, transforming growth factor-β1 (TGF-β1) and IL-10 expression and NF-κB/p65, extracellular signal-regulated kinase (ERK), C-Jun N-terminal kinase (JNK) and P38 expression. Application of NP to DRG in rats induced mechanical allodynia, increased the expression of pro-inflammatory factors (TNF-α and IL-1β), NF-κB/p65, the phosphorylated-ERK (p-ERK), -JNK (p-JNK) and -P38 (p-p38) and decreased the expression of anti-inflammatory cytokines (TGF-β1 and IL-10) in the ipsilateral lumbar (L4-L6) segment of spinal dorsal horns. Intrathecal injection of LXA4 alleviated the development of neuropathic pain, inhibited the upregulation of pro-inflammatory cytokines (TNF-α and IL-1β), upregulated the expression of anti-inflammatory cytokines (TGF-β1 and IL-10) and attenuated the activation of NF-κB/p65, p-ERK, p-JNK, but not p-p38, in a dose-dependent manner. In this study, we have demonstrated that LXA4 potently alleviate radicular pain in a rat model of non-compressive lumbar disc herniation. The anti-inflammatory and pro-resolution properties of LXA4 have shown a great promise for the management of radicular pain caused by intervertebral disc herniation.
authors.affiliation: Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, PR China.
authors.forename: G-S
authors.initials: GS
authors.lastname: Miao
authors.affiliation: Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, PR China.
authors.forename: Z-H
authors.initials: ZH
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, The Sixth People's Hospital of Jinan, Zhangqiu, Shandong, PR China.
authors.forename: S-X
authors.initials: SX
authors.lastname: Wei
authors.affiliation: Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, PR China.
authors.forename: J-G
authors.initials: JG
authors.lastname: Luo
authors.affiliation: Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, PR China.
authors.forename: Z-J
authors.initials: ZJ
authors.lastname: Fu
authors.affiliation: Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, PR China. Electronic address: suntaosdph@163.com.
authors.forename: T
authors.initials: T
authors.lastname: Sun
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D055959:Intervertebral Disc Degeneration / Q000503:physiopathology*; D007405:Intervertebral Disc Displacement / Q000503:physiopathology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D044045:Lipoxins / Q000494:pharmacology*; D009437:Neuralgia / Q000188:drug therapy* / Q000503:physiopathology*; D010147:Pain Measurement; D017207:Rats, Sprague-Dawley; D066148:Spinal Cord Dorsal Horn / Q000187:drug effects / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D044045:Lipoxins; D051996:Transcription Factor RelA; C040527:lipoxin A4; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: inflammation; intervertebral disc herniation; lipoxin A(4); radicular pain; rat; spinal cord