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An approach to targeting Nav1.7 for pain sensations
The Journal of Clinical Investigation
|July 15, 2025
Summary
Researchers discovered fibroblast growth factor 13 (FGF13) increases Nav1.7 channel activity and pain. A new compound, PW164, selectively targets FGF13 and Nav1.7, offering a promising strategy for nonaddictive pain relief.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Pain management is a significant challenge due to limited efficacy and side effects of current treatments.
- The Nav1.7 voltage-gated sodium channel is a key target for developing nonaddictive analgesics.
- Developing effective Nav1.7 blockers has proven difficult.
Purpose of the Study:
- To identify novel strategies for modulating Nav1.7 channel activity.
- To investigate the role of intrinsic modulators in nociceptor excitability and pain.
- To discover new therapeutic targets for pain management.
Main Methods:
- Identification of fibroblast growth factor 13 (FGF13) as a regulator of Nav1.7.
- Assessment of FGF13's effect on Nav1.7 currents and nociceptor excitability.
- Screening for and identification of a selective FGF13-Nav1.7 attenuator (PW164).
Main Results:
- Fibroblast growth factor 13 (FGF13) was identified as a factor that increases Nav1.7 channel activity, nociceptor excitability, and pain.
- Compound PW164 demonstrated selective attenuation of FGF13-mediated Nav1.7 activity.
- PW164 exhibited significant analgesic activity in preclinical models.
Conclusions:
- Targeting intrinsic modulators of Nav1.7, such as FGF13, represents a novel therapeutic strategy for pain.
- Compound PW164 shows potential as a nonaddictive analgesic by selectively inhibiting the FGF13-Nav1.7 pathway.
- These findings open new avenues for developing effective pain management therapies.
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