| First Author | Harada Y | Year | 2019 |
| Journal | Pain | Volume | 160 |
| Issue | 9 | Pages | 2050-2062 |
| PubMed ID | 31095099 | Mgi Jnum | J:295798 |
| Mgi Id | MGI:6454466 | Doi | 10.1097/j.pain.0000000000001596 |
| Citation | Harada Y, et al. (2019) Cathepsin E in neutrophils contributes to the generation of neuropathic pain in experimental autoimmune encephalomyelitis. Pain 160(9):2050-2062 |
| abstractText | Pain is a frequent and disabling symptom in patients with multiple sclerosis (MS); however, the underlying mechanisms of MS-related pain are not fully understood. Here, we demonstrated that cathepsin E (CatE) in neutrophils contributes to the generation of mechanical allodynia in experimental autoimmune encephalomyelitis, an animal model of MS. We showed that CatE-deficient (CatE) mice were highly resistant to myelin oligodendrocyte glycoprotein (MOG35-55)-induced mechanical allodynia. After MOG35-55 immunization, neutrophils immediately accumulated in the dorsal root ganglion (DRG). Adoptive transfer of MOG35-55-stimulated wild-type neutrophils into the dorsal root ganglion induced mechanical allodynia in the recipient C57BL/6 mice. However, the pain threshold did not change when MOG35-55-stimulated CatE neutrophils were transferred into the recipient C57BL/6 mice. MOG35-55 stimulation caused CatE-dependent secretion of elastase in neutrophils. Behavioral analyses revealed that sivelestat, a selective neutrophil elastase inhibitor, suppressed mechanical allodynia induced by adoptively transferred MOG35-55-stimulated neutrophils. MOG35-55 directly bound to toll-like receptor 4, which led to increased production of CatE in neutrophils. Our findings suggest that inhibition of CatE-dependent elastase production in neutrophil might be a potential therapeutic target for pain in patients with MS. |
