| First Author | Zhang P | Year | 2022 |
| Journal | Fundam Clin Pharmacol | Volume | 36 |
| Issue | 2 | Pages | 262-276 |
| PubMed ID | 34904278 | Mgi Jnum | J:344431 |
| Mgi Id | MGI:7576793 | Doi | 10.1111/fcp.12742 |
| Citation | Zhang P, et al. (2022) Activation of spinal ephrin-B3/EphBs signaling induces hyperalgesia through a PLP-mediated mechanism. Fundam Clin Pharmacol 36(2):262-276 |
| abstractText | Ephrin B/EphB signaling pathway is involved in the regulation of pain caused by spinal cord injury. However, the role of ephrin-B3/EphBs signaling in regulation of nociceptive information is poorly understood. In the present study, formalin-induced inflammatory pain, mechanical allodynia and thermal hyperalgesia, was measured using Efnb3 mutant mice (Efnb3(-/-) ) and wild-type (Efnb3(+/+) ) mice. The spinal cord (L4-6) was selected for molecular and cellular identification by western blotting and immunofluorescence. Efnb3 mutant mice showed a significant increased the thermal and mechanical threshold, followed by aberrant thin myelin sheath. Furthermore, expression of proteolipid protein (PLP) was significantly lower in L4-6 spinal cord of Efnb3(-/-) mice. These morphological and behavioral abnormalities in mutant mice were rescued by conditional knock-in of wild-type ephrin-B3. Intrathecal administration of specific PLP siRNA significantly increased the thermal and mechanical threshold hyperalgesia in wild-type mice. However, overexpressing PLP protein by AAV9-PLP could decrease the sensitivity of mice to thermal and mechanical stimuli in Efnb3(-/-) mice, compared with scrabble Efnb3(-/-) mice. Further, Efnb3(lacz) mice, which have activities to initiate forward signaling, but transduce reverse signals by ephrin-B3, shows normal acute pain behavior, compared with wild type mice. These findings indicate that a key molecule Efnb3 act as a prominent contributor to hyperalgesia and essential roles of ephrin-B3/EphBs in nociception through a myelin-mediated mechanism. |
