Pain in sickle cell disease: current and potential translational therapies

Endoplasmic Reticulum Stress in Chemotherapy-Induced Peripheral Neuropathy: Emerging Role of Phytochemicals

“…The underlying mechanism is not yet fully explored, and cerebellar affection might play a role evidenced by the loss of Purkinje cells in the cerebellum [ 38 ]. Interestingly, Purkinje cell damage and hyperalgesia have been demonstrated in transgenic mice with sickle cell disease (SCD), featuring neuropathic pain with several features reminiscent of CIPN [ 39 , 40 ]. Sickle mice showed altered stance instability and dynamic gait parameters similar to those found in chemotherapy-induced neuropathy.…”

Pain mechanisms in sickle cell disease. Are we closer to a breakthrough?

“…Pain is a hallmark of SCD and is a major cause of morbidity in patients, with significant negative effects on quality of life. Acute pain, a characteristic and frequent complication of SCD, is usually generated by vaso-occlusive episodes, 2 in which vaso-occlusion and ensuing ischemia-reperfusion processes generate the production of multiple pro-inflammatory molecules and pain mediators, including eicosanoids and bradykinin. 3 , 4 The causes of chronic pain, previously reported to affect approximately 30% of adults with SCD on an almost daily basis, 5 are less clear in SCD, but may arise from central sensitization due to nociceptive signaling from the periphery to the central nervous system, leading to pain hypersensitivity, although there is also evidence for a contribution of neuropathic pain.…”

“…The management of pain, both acute and chronic, in SCD often requires the use of opioids for analgesia, but challenges can arise from the side-effects associated with such medications, opioid-induced hyperalgesia and, sadly, some provider bias. 2 As such, the search continues to identify effective non-opioid-based analgesic therapeutic approaches for pain in SCD. The use of COX-2 inhibitors has previously been suggested for managing chronic pain in SCD, 2 , 8 especially given evidence of elevated COX-2 expression and/or activity in the leukocytes of mice and patients with SCD, 1 , 6 , 9 with Khasabova et al previously reporting on the analgesic efficacy of R -flurbiprofen in mice with SCD.…”

“… 2 As such, the search continues to identify effective non-opioid-based analgesic therapeutic approaches for pain in SCD. The use of COX-2 inhibitors has previously been suggested for managing chronic pain in SCD, 2 , 8 especially given evidence of elevated COX-2 expression and/or activity in the leukocytes of mice and patients with SCD, 1 , 6 , 9 with Khasabova et al previously reporting on the analgesic efficacy of R -flurbiprofen in mice with SCD. 6 However, observations in the latest study by Khasabova and colleagues indicate that elevation of 2-AG, upstream of COX-2, may be specific to those SCD mice displaying hyperalgesia, 1 meaning that approaches that can decrease DAGLβ-mediated biosynthesis of 2-AG could provide targeted relief for hyperalgesia in SCD, with theoretically fewer side effects than those of COX inhibitors.…”

Chronic opioid use in patients with sickle cell disease

“…In the acute setting, SCD patients may have painful crises that require hospitalization [2]. However, these patients also suffer chronic pain, the etiology of which is not fully understood [3].…”