Updated mechanisms underlying sickle cell disease-associated pain.

• Transient receptor potential vanilloid 1 is activated and sensitized in the dorsal root ganglion neurons through multiple mechanisms under sickle cell disease-associated pain conditions. • Endothelin-1 and endothelin type A receptor are upregulated in the dorsal root ganglion neurons from the sickle cell disease mice. • Both transient receptor potential vanilloid 1 and endothelin-1/endothelin type A receptor are required for the development of sickle cell disease-associated pain. • Cannabinoids might be used as a therapeutical approach, but remains to be confirmed in the management of sickle cell disease-associated pain. Sickle cell disease (SCD) is one of the most common severe genetic diseases around the world. A majority of SCD patients experience intense pain, leading to hospitalization, and poor quality of life. Opioids form the bedrock of pain management, but their long-term use is associated with severe side effects including hyperalgesia, tolerance and addiction. Recently, excellent research has shown some new potential mechanisms that underlie SCD-associated pain. This review focused on how transient receptor potential vanilloid 1, endothelin-1/endothelin type A receptor, and cannabinoid receptors contributed to the pathophysiology of SCD-associated pain. Understanding these mechanisms may open a new avenue in managing SCD-associated pain and improving quality of life for SCD patients. [ABSTRACT FROM AUTHOR]