Role of SCN1B in susceptibility to neuropathic pain

Ended Project Grant Awarded

Award ID
R21NS136075
Recipient
Awarding agency
Obligated
$415,519

Award facts

Assistance listing
93.279 Drug Use and Addiction Research Programs
Completion date
Place of performance
Berkeley, CA 94720, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
This goal of this R21 project is to jumpstart mechanistic research on the role in neuropathic pain of SCN1B, an understudied druggable protein. Neuropathic pain is a debilitating, chronic condition that represents a major medical burden in the US. Current standards of care are ineffective both for preventing pain chronicity after nerve injury, and for providing long-term relief for neuropathic pain. Individuals show different susceptibilities to neuropathic pain and experience diverse sensory symptoms; however, little is known about the genetic factors that predispose individuals to chronic sensory dysfunction. Thus, there is a need to understand the mechanisms that that underlie neuropathic pain, because such molecules are potential therapeutic targets and biomarkers of susceptibility. In a screen for natural genetic variation among genetically distinct mouse strains, we identified SCN1B as a top candidate susceptibility gene for tactile hypersensitivity in a mouse model of paclitaxel-induced neuropathic pain (pipn). The SCN1B gene encodes the auxiliary Β1 subunit of voltage-gated NA+ channels, which are key regulators of neuronal excitability because they mediate the upstroke of the action potential. SCN1B expression is highly enriched in myelinated mechanosensory neurons that provide sensory drive for tactile allodynia in persistent pain. Based on these results, this project's central hypothesis is that SCN1B plays a key role in the development of tactile allodynia in mouse models of neuropathic pain by governing the excitability of mechanosensory neurons. This hypothesis will be tested with a combination of sensory neuron-specific SCN1B knockout mice, electrophysiological studies and a battery of behavioral tests for somatosensory and motor behaviors. Aims are to: 1) determine whether SCN1B is a susceptibility factor for neuropathic pain in a mouse cipn model; and 2) determine whether SCN1B is required for the development of neuropathic pain in a spared- nerve injury model. If successful, this research will generate essential pilot data that will rapidly catalyze future research to elucidate mechanisms through which SCN1B promote neuropathic pain, develop SCN1B as a new therapeutic target, and validate SCN1B as a biomarker for neuropathic-pain susceptibility.

Quick answers

Who received award R21NS136075?

R21NS136075 was awarded to The Regents Of The University Of California by National Institute of Neurological Disorders and Stroke (National Institutes of Health) on June 19, 2024.

How much is award R21NS136075 worth?

$415,519 has been obligated on R21NS136075.

On GovTribe

See this award's full record

  • Every transaction and subaward
  • The recipient's other awards and teaming partners
  • Similar grant awards
  • Ask GovTribe AI about this award
Try for free Login