The NLRP3-related inflammasome modulates pain behavior in a rat model of trigeminal neuropathic pain
| Autor: | Jianyun Ge, Jie Song, Jian-Lin Ge, Cao Liang, Boxiang Du, Sun Xin, Xuefeng Yang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Programmed cell death Inflammasomes Inferior alveolar nerve Pharmacology 030226 pharmacology & pharmacy Pyrin domain General Biochemistry Genetics and Molecular Biology Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation NLR Family Pyrin Domain-Containing 3 Protein Medicine Animals General Pharmacology Toxicology and Pharmaceutics Medulla Oblongata integumentary system Microglia business.industry Brain Inflammasome General Medicine Trigeminal Neuralgia Rats Posterior Horn Cells 030104 developmental biology medicine.anatomical_structure Hyperalgesia Trigeminal Nerve Diseases Neuropathic pain Cytokines Neuralgia Implant business medicine.drug |
| Zdroj: | Life sciences. 277 |
| ISSN: | 1879-0631 |
| Popis: | Aims Nod-like receptor family pyrin domain containing 3 (NLRP3) may play an important role in neuropathic pain. Treatment for trigeminal neuropathic pain remains a challenge, as common drugs either do not demonstrate beneficial therapeutic effects or induce intolerance in patients. Main methods In a rat model of trigeminal neuropathic pain, pain caused by the malpositioning of dental implants is similar to that experienced by humans. We used masculine Sprague-Dawley rats with inferior alveolar nerve damage as a model to investigate the differential regulation of NLRP3. First, we confirmed the level of NLRP3 in the medullary dorsal horn and variation of pain response behavior after silencing the expression of NLRP3 inflammasome bodies in rats with trigeminal neuropathic pain. Second, under localized anesthesia, we extracted the lower left second molar, implanted a micro-dental implant, and deliberately injured the inferior alveolar nerve. Key findings After nerve damage, the level of NLRP3-related inflammasomes was upregulated in microglia and the expression of a component of the inflammasome gradually increased during postoperative days 3–21. The suppression of adenovirus-shRNA-NLRP3 on postoperative day 1 markedly inhibited the expression of pro-inflammatory cytokines and the activation of the inflammasome and mechanical allodynia. Furthermore, it attenuated cell death in microglia, as evidenced by increased Bcl-2, Bcl-xL, Bax, and Bik expression. Significance The level of NLRP3 in the dorsal horn is a pivotal factor in trigeminal neuropathic pain, and inhibition of the early expression of NLRP3 might serve as a potential therapeutic approach. |
| Databáze: | OpenAIRE |
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