2015 Fiscal Year Final Research Report
Identification and functional analysis of new molecules that elicit hyperalgesia
Project/Area Number |
26670643
|
Research Category |
Grant-in-Aid for Challenging Exploratory Research
|
Allocation Type | Multi-year Fund |
Research Field |
Neurosurgery
|
Research Institution | Osaka University |
Principal Investigator |
|
Project Period (FY) |
2014-04-01 – 2016-03-31
|
Keywords | 疼痛 / 神経 |
Outline of Final Research Achievements |
We demonstrate that Netrin-4, a member of the axon guidance molecule family, was expressed in dorsal horn inner lamina II excitatory interneurons of rat spinal cord. A similar expression pattern for Netrin-4 was also observed in human spinal cord. Behavioral analysis revealed that Netrin-4 mutant rats showed abolishment of tactile and heat hyperalgesia that occurs after peripheral nerve injury or inflammation. Transient suppression of Netrin-4, or its receptor Unc5B, after injury could prevent allodynia. Conversely, intrathecal Netrin-4 protein administration to naiive rats enhanced excitatory synaptic transmission in the dorsal horn and induced allodynia, suggesting Netrin-4 is involved in spinal sensitization. Furthermore, Unc5B receptor and activation of tyrosine phosphatase SHP2 mediated Netrin-4-induced pain signal in the spinal cord.
|
Free Research Field |
神経科学
|