Hyaluronan modulates TRPV1 channel opening, reducing peripheral nociceptor activity and pain
Rebeca Caires1, Enoch Luis1, Francisco J Taberner2
1Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, San Juan de Alicante, 03550 Alicante, Spain.
Nature Communications
|August 28, 2015
Summary
Hyaluronan (HA) reduces pain by modulating TRPV1 channels. This extracellular matrix molecule stabilizes the TRPV1 channel in its closed state, decreasing nerve cell excitability and pain responses.
Area of Science:
- Neuroscience
- Biochemistry
- Pain Research
Background:
- Hyaluronan (HA) is a key component of the extracellular matrix, particularly in synovial fluid, where it buffers mechanical forces.
- Nociceptor nerve endings transmit pain signals, and their excitability is crucial in pain perception.
Purpose of the Study:
- To investigate the role of Hyaluronan (HA) in modulating polymodal transient receptor potential vanilloid subtype 1 (TRPV1) channels.
- To determine how HA affects the function of TRPV1 channels and subsequent pain signaling.
Main Methods:
- Utilized recombinant systems, cultured dorsal root ganglia (DRG) neurons from mice, and in vivo experiments.
- Assessed HA's effect on TRPV1 channel responses to heat, pH, and capsaicin (CAP).
- Evaluated HA's impact on neuronal firing and sensitization by bradykinin, as well as nocifensive behaviors in vivo.
Main Results:
- Hyaluronan (HA) was found to diminish heat, pH, and capsaicin (CAP) responses by stabilizing the closed state of TRPV1 channels.
- In DRG neurons, HA decreased TRPV1-mediated impulse firing and bradykinin-induced channel sensitization.
- Subcutaneous and intra-articular HA injections in animal models reduced heat and capsaicin-evoked nocifensive responses and nerve fiber discharge.
Conclusions:
- Extracellular Hyaluronan (HA) acts as a regulator of TRPV1 channel excitability.
- HA reduces the activity of peripheral nociceptor endings by modulating TRPV1 channels, thereby contributing to pain reduction.
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