Functional Recovery after Peripheral Nerve Injury is Dependent on the Pro-Inflammatory Cytokines IL-1β and TNF: Implications for Neuropathic Pain
| Autor: | Juan Pablo de Rivero Vaccari, Steve Lacroix, Robert W. Keane, Mohammed Filali, Bradley J. Kerr, Sylvain Nadeau, Denis Soulet, Ji Zhang, Yoichiro Iwakura, Serge Rivest |
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| Rok vydání: | 2011 |
| Předmět: |
Time Factors
Neutrophils medicine.medical_treatment Interleukin-1beta Pharmacology Antibodies Proinflammatory cytokine Mice Sciatica Imaging Three-Dimensional medicine Animals Antigens Ly Axon Mice Knockout Analysis of Variance Interleukin-16 CD11b Antigen business.industry General Neuroscience Receptors Interleukin-1 Recovery of Function Articles Sciatic nerve injury Flow Cytometry medicine.disease Sciatic Nerve Mice Inbred C57BL Disease Models Animal Cytokine medicine.anatomical_structure Gene Expression Regulation Hyperalgesia Receptors Tumor Necrosis Factor Type I Anesthesia Neuropathic pain Peripheral nerve injury Sciatic nerve medicine.symptom business |
| Zdroj: | The Journal of Neuroscience. 31:12533-12542 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.2840-11.2011 |
| Popis: | IL-1β and TNF are potential targets in the management of neuropathic pain after injury. However, the importance of the IL-1 and TNF systems for peripheral nerve regeneration and the mechanisms by which these cytokines mediate effects are to be fully elucidated. Here, we demonstrate that mRNA and protein levels of IL-1β and TNF are rapidly upregulated in the injured mouse sciatic nerve. Mice lacking both IL-1β and TNF, or both IL-1 type 1 receptor (IL-1R1) and TNF type 1 receptor (TNFR1), showed reduced nociceptive sensitivity (mechanical allodynia) compared with wild-type littermates after injury. Microinjecting recombinant IL-1β or TNF at the site of sciatic nerve injury in IL-1β- and TNF-knock-out mice restored mechanical pain thresholds back to levels observed in injured wild-type mice. Importantly, recovery of sciatic nerve function was impaired in IL-1β-, TNF-, and IL-1β/TNF-knock-out mice. Notably, the infiltration of neutrophils was almost completely prevented in the sciatic nerve distal stump of mice lacking both IL-1R1 and TNFR1. Systemic treatment of mice with an anti-Ly6G antibody to deplete neutrophils, cells that play an essential role in the genesis of neuropathic pain, did not affect recovery of neurological function and peripheral axon regeneration. Together, these results suggest that targeting specific IL-1β/TNF-dependent responses, such as neutrophil infiltration, is a better therapeutic strategy for treatment of neuropathic pain after peripheral nerve injury than complete blockage of cytokine production. |
| Databáze: | OpenAIRE |
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