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Contribution of CD137L to Sensory Hypersensitivity in a Murine Model of Neuropathic Pain
| Content Provider | Semantic Scholar |
|---|---|
| Author | Wakley, Alexa A. Leeming, Reno Malon, Jenn Arabatzis, Taxiarhia J. Koh, Woon Yuen Cao, Ling Fei |
| Copyright Year | 2018 |
| Abstract | CD137L (4-1BBL) is a costimulatory molecule whose signaling can promote monocyte/macrophage functions; however, CD137L-mediated microglial response and its role in neuropathic pain remain unknown. We investigated CD137L following peripheral nerve injury-induced neuropathic pain using a spinal nerve L5 transection (L5Tx) murine model in both sexes. First, C57BL/6_CD137L knock-out (KO) mice displayed decreased mechanical and diminished heat hypersensitivity compared to wild-type (WT) controls, beginning on day 3 to up to day 35 post-L5Tx. Purified anti-mouse CD137L neutralizing monoclonal antibody (0.1 or 0.5 µg) was also used to identify CD137L's window of action in BALB/c mice. Anti-CD137L antibody was intrathecally administered either from day 0 (before surgery) to day 7 (early treatment), or from day 6 to 13 post-L5Tx (late treatment), and nociceptive thresholds were assessed before surgery to up to day 35 post-surgery. Early treatment with anti-CD137L reduced L5Tx-induced mechanical but not heat hypersensitivity, while later treatment did not alter either sensitivity. Pro- versus anti-inflammatory responses within the lumbar spinal cord following L5Tx were further evaluated via quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) in time-course studies. Following L5Tx, female CD137L KO mice did not show increased iNOS mRNA and had reduced numbers of IL-1β+ cells compared to WT. At 21 d post-surgery, CD137L KO mice had higher total numbers of arginase (Arg)-1+ cells and Arg-1+ microglia. Altogether, results indicate that spinal cord CD137L contributes to the development of peripheral nerve injury-induced neuropathic pain, which may be in part mediated through CD137L's modulation of the pro- and anti-inflammatory balance within the spinal cord. |
| Starting Page | 7947 |
| Ending Page | 7952 |
| Page Count | 6 |
| File Format | PDF HTM / HTML |
| PubMed reference number | 30417077v1 |
| Alternate Webpage(s) | https://doi.org/10.1523/ENEURO.0218-18.2018 |
| DOI | 10.1523/eneuro.0218-18.2018 |
| Journal | eNeuro |
| Volume Number | 5 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | ARGINASE Anti-Inflammatory Agents CD276 Antigen Drug Allergy Immunohistochemistry Knock-out Microglia Monoclonal Antibodies Monocytes Neuralgia Peripheral Nerve Injuries Peripheral Nerves Spinal Cord Spinal nerve structure TNFSF9 gene inflammatory response nerve injury |
| Content Type | Text |
| Resource Type | Article |
