The Role of the Protein Tyrosine Phosphatase SHP-1 in TRPV1-mediated Pain Behavior
Session Number
Project ID: MEDH 20
Advisor(s)
Dr. Adrienn Markovics, Rush University Medical Center
Discipline
Medical and Health Sciences
Start Date
17-4-2024 8:35 AM
End Date
17-4-2024 8:50 AM
Abstract
The capsaicin receptor TRPV1 is expressed in pain-sensing neurons and has been an attractive drug target for pain control. However, its physiological function such as regulating normal body temperature and heat sensation made TRPV1-targeting drug development challenging. Previous studies showed that the protein tyrosine phosphatase enzyme SHP-1 can modulate TRPV1 in the dorsal root ganglion (DRG). Our aim was to investigate the effect of genetically increased SHP-1 activity on capsaicin-induced neuronal responses and pain behavior in mice. First, capsaicin-induced responses of cultured DRG neurons from wildtype (WT) and SHP-1 overexpressing (Shp1-Tg) mice were compared. Second, capsaicin paw injection was performed, and the time spent with paw licking, and paw withdrawal threshold to mechanical stimulation were evaluated as measures of pain behavior. Interestingly, capsaicin-induced neuronal responses in the DRG of Shp1-Tg mice were reduced. While paw licking time and paw thickness were not significantly different after capsaicin injection, mechanical allodynia was significantly reduced in Shp1-Tg mice compared to WTs. Our results suggest that TRPV1 modulation by increased SHP-1 activity might represent a novel approach to control pain without the limiting side effects of TRPV1 blocking drugs and warrant further investigation into the SHP-1/TRPV1 pathway.
The Role of the Protein Tyrosine Phosphatase SHP-1 in TRPV1-mediated Pain Behavior
The capsaicin receptor TRPV1 is expressed in pain-sensing neurons and has been an attractive drug target for pain control. However, its physiological function such as regulating normal body temperature and heat sensation made TRPV1-targeting drug development challenging. Previous studies showed that the protein tyrosine phosphatase enzyme SHP-1 can modulate TRPV1 in the dorsal root ganglion (DRG). Our aim was to investigate the effect of genetically increased SHP-1 activity on capsaicin-induced neuronal responses and pain behavior in mice. First, capsaicin-induced responses of cultured DRG neurons from wildtype (WT) and SHP-1 overexpressing (Shp1-Tg) mice were compared. Second, capsaicin paw injection was performed, and the time spent with paw licking, and paw withdrawal threshold to mechanical stimulation were evaluated as measures of pain behavior. Interestingly, capsaicin-induced neuronal responses in the DRG of Shp1-Tg mice were reduced. While paw licking time and paw thickness were not significantly different after capsaicin injection, mechanical allodynia was significantly reduced in Shp1-Tg mice compared to WTs. Our results suggest that TRPV1 modulation by increased SHP-1 activity might represent a novel approach to control pain without the limiting side effects of TRPV1 blocking drugs and warrant further investigation into the SHP-1/TRPV1 pathway.