Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Neurobiological mechanisms of pain in sickle cell disease. 2123 26

Pain is the leading cause of emergency department visits, hospitalizations, and daily suffering in individuals with sickle cell disease (SCD). The pathologic mechanisms leading to the perception of pain during acute RBC sickling episodes and development of chronic pain remain poorly understood and ineffectively treated. We provide the first study that explores nociceptor sensitization mechanisms that contribute to pain behavior in mice with severe SCD. Sickle mice exhibit robust behavioral hypersensitivity to mechanical, cold, and heat stimuli. Mechanical hypersensitivity is further exacerbated when hypoxia is used to induce acute sickling. Behavioral mechanical hypersensitivity is mediated in part by enhanced excitability to mechanical stimuli at both primary afferent peripheral terminal and sensory membrane levels. In the present study, inhibition of the capsaicin receptor transient receptor potential vanilloid 1 (TRPV1) with the selective antagonist A-425619 reversed the mechanical sensitization at both primary afferent terminals and isolated somata, and markedly attenuated mechanical behavioral hypersensitivity. In contrast, inhibition of TRPA1 with HC-030031 had no effect on mechanical sensitivity. These results suggest that the TRPV1 receptor contributes to primary afferent mechanical sensitization and a substantial portion of behavioral mechanical hypersensitivity in SCD mice. Therefore, TRPV1-targeted compounds that lack thermoregulatory side effects may provide relief from pain in patients with SCD.
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PMID:Transient receptor potential vanilloid 1 mediates pain in mice with severe sickle cell disease. 2170 90

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.
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PMID:Updated mechanisms underlying sickle cell disease-associated pain. 3150 41