Peripheral transient receptor potential vanilloid type 4 hypersensitivity contributes to chronic sickle cell disease pain. Pain 2023 Aug 01;164(8):1874-1886
Date
03/11/2023Pubmed ID
36897169Pubmed Central ID
PMC10363186DOI
10.1097/j.pain.0000000000002889Scopus ID
2-s2.0-85163868805 (requires institutional sign-in at Scopus site) 3 CitationsAbstract
Debilitating pain affects the lives of patients with sickle cell disease (SCD). Current pain treatment for patients with SCD fail to completely resolve acute or chronic SCD pain. Previous research indicates that the cation channel transient receptor potential vanilloid type 4 (TRPV4) mediates peripheral hypersensitivity in various inflammatory and neuropathic pain conditions that may share similar pathophysiology with SCD, but this channel's role in chronic SCD pain remains unknown. Thus, the current experiments examined whether TRPV4 regulates hyperalgesia in transgenic mouse models of SCD. Acute blockade of TRPV4 alleviated evoked behavioral hypersensitivity to punctate, but not dynamic, mechanical stimuli in mice with SCD. TRPV4 blockade also reduced the mechanical sensitivity of small, but not large, dorsal root ganglia neurons from mice with SCD. Furthermore, keratinocytes from mice with SCD showed sensitized TRPV4-dependent calcium responses. These results shed new light on the role of TRPV4 in SCD chronic pain and are the first to suggest a role for epidermal keratinocytes in the heightened sensitivity observed in SCD.
Author List
Ehlers VL, Sadler KE, Stucky CLAuthor
Cheryl L. Stucky PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Anemia, Sickle CellAnimals
Antineoplastic Agents
Chronic Pain
Hyperalgesia
Mice
Mice, Transgenic
TRPV Cation Channels
