Accession Number:

AD1000375

Title:

Novel Target for Ameliorating Pain and Other Problems after SCI: Spontaneous Activityin Nociceptors

Descriptive Note:

Technical Report,15 Sep 2014,14 Sep 2015

Corporate Author:

University of Texas Health Science Center Houston

Personal Author(s):

Report Date:

2015-10-01

Pagination or Media Count:

15.0

Abstract:

The purpose of the project is test the hypothesis that interventions that reduce the function of a sodium ion channel, Nav1.8,that is selectively expressed in primary afferent neurons especially nociceptors ameliorate reflex hypersensitivity and pathological pain-related motivationalcognitive alterations caused by traumatic spinal cord injury SCI. The first phase of the project was accomplished, with a major paper published describing how effective antisense knockdown of Nav1.8 eliminates SCI-induced spontaneous activity in nociceptors, reverses mechanical and heat hypersensitivity of hindlimb withdrawal reflexes, and ameliorates ongoing, spontaneous pain. During the past year we have investigated effects of a selective Nav1.8 antagonist, A-803467, on heat hypersensitivity, mechanical hypersensitivity, spontaneous pain, and anxiety. We have also found that blockade of the cAMP-PKA signaling pathway, known to enhance Nav1.8 activity, eliminates SCI-induced spontaneous activity. These studies will be completed during the 6-month extension without funds. During the past two quarters we found evidence that an inexpensive but nonspecific Nav1.8 inhibitor, ambroxol, does not reduce pain-associated behavior, while the more specific antagonist, A-803467, continues to show promise not only for reducing hyperreflexia, spontaneous pain, and evoked pain, but also anxiety after SCI.

Subject Categories:

Distribution Statement:

APPROVED FOR PUBLIC RELEASE