Early insights into the neurobiology of pain in sickle cell disease: A systematic review of the literature

Abstract

Novel insights into the neurobiology of sickle cell disease (SCD) pain have recently been discovered. We systematically reviewed the literature focusing on original research that examined the biology of pain in SCD and/or addressed assessment or treatment of neuropathic pain in SCD. This review of 15 articles that met inclusion criteria provides epidemiological, basic and clinical data that support central and/or peripheral nervous system abnormalities likely contribute to sickle cell pain. Continued basic and clinical investigation into pain neurobiology is imperative to translate these discoveries into novel ways to assess and treat neuropathic pain and decrease patient suffering.

Sickle cell disease: a natural model of acute and chronic pain

“…[7; 17] Quantitative sensory testing in SCD patients reveals they have increased sensitivity to thermal and/or mechanical stimuli, and fMRI changes and windup suggest that there are both peripheral and central nervous system abnormalities. [8; 9; 17; 25; 45] These data suggest a complex etiology to SCD pain including ischemic, inflammatory and neuropathic components. The tissue sources of pain range from cutaneous to deep foci.…”

Substance P is increased in patients with sickle cell disease and associated with haemolysis and hydroxycarbamide use

“…(Brandow et al , 2010; Brousseau et al 2010; Panepinto et al , 2005; Smith et al , 2008) Increasing evidence in both murine models and patients with SCD suggests that abnormalities in the peripheral and central nervous systems contribute to the development of chronic pain in SCD that is sustained over time. (Brandow et al , 2015; Darbari et al , 2015; Hillery et al , 2011; Kohli et al , 2010; Vincent et al , 2013) Patients with SCD experience increased pain to thermal (cold, heat) stimuli compared to healthy controls(Brandow et al , 2015; Brandow et al , 2013; Ezenwa et al , 2016; Jacob et al , 2015; O'Leary et al , 2014) and report features of neuropathic pain on validated screening questionnaires. (Brandow et al , 2014; Ezenwa et al , 2016) Collectively, these data illustrate the complex nature of sickle cell pain that probably includes inflammatory, neuropathicand other aetiologies that ultimately drive the pain.…”

Substance P and sickle cell disease—a marker for pain and novel therapeutic approaches

“…Inhibition was demonstrated by cannabinoid receptor antagonists the mast cell inhibitors cromolyn sodium and imatinib, and the mechanical pain receptors, the TRPV family of transient receptor potential cation channels. A single clinical trial of trifluoperazine, an anti-psychotic that inhibits calcium calmodulin protein kinase II alpha, was done in 18 SCD adults and this drug showed safety and decreased pain intensity (Reviewed in Brandow et al 2015). …”