Abstract
Pain is a frequent complaint of people living with sickle cell disease (SCD); however, the neurobiology of pain in SCD remains poorly understood. Whereas this pain has been thought to be primarily related to visceral and somatic tissue injury subsequent to vaso-occlusion events, emerging evidence from human and animal studies has suggested that a component of SCD pain may be related to neuropathic processes. Significant knowledge has been obtained from studies of molecular and neurobiological mechanisms leading to and maintaining neuropathic pain. Some of the most promising evidence has implicated major roles of protein kinase C and Ca2+/calmodulin-dependent protein kinase II, and their interaction with the N-methyl-D-aspartate receptors and the transient receptor potential vanilloid 1 receptor in the development of neuropathic pain. The latest evidence from our studies suggests that these pathways are important for SCD pain as well. Coupled with emerging animal models of SCD pain, we can now start to elucidate neurobiological mechanisms underlying pain in SCD, which may lead to better understanding and effective therapies.