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Endothelin-1 induced desensitization in primary afferent neurons
Terika P Smith1, Sherika N Smith1, Sarah M Sweitzer2
1Department of Pharmacology, Physiology and Neuroscience, University of South Carolina, Columbia, SC, United States.
Neuroscience Letters
|September 16, 2014
Summary
Endothelin-1 (ET-1) priming desensitizes primary afferent neurons to subsequent ET-1 and capsaicin challenges. This suggests ET-1
Area of Science:
- Neuroscience
- Pain Research
- Cellular Biology
Background:
- Endothelin-1 (ET-1) is a pain-inducing agent linked to sickle cell disease (SCD) vaso-occlusive episodes (VOEs).
- Previous research indicated ET-1 priming sensitizes responses to capsaicin.
- The precise neuronal level of ET-1-induced sensitization remained unclear.
Purpose of the Study:
- To investigate whether ET-1 priming-induced sensitization occurs at the primary afferent neuron level.
- To examine the direct effects of ET-1 on primary afferent neurons.
Main Methods:
- Utilized calcium imaging in cultured dorsal root ganglion (DRG) neurons.
- Assessed intracellular calcium ([Ca(2+)]i) transients in response to ET-1 and capsaicin.
- Administered priming doses of ET-1 at varying intervals before challenge doses.
Main Results:
- ET-1 induced [Ca(2+)]i transients in unprimed DRG neurons.
- Priming with ET-1 attenuated subsequent ET-1-induced [Ca(2+)]i transients, regardless of priming interval (0-4 days).
- ET-1 priming also decreased capsaicin-induced [Ca(2+)]i transients.
Conclusions:
- ET-1 priming exerts a desensitizing effect on primary afferent neurons.
- This desensitization impacts responses to both ET-1 and capsaicin challenges.
- Findings indicate primary afferent neurons are a key site for ET-1's modulatory effects on pain signaling.
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