Characteristics and potential biomarkers of adult sickle cell patients with chronic pain

Abstract

Objectives In this study, we investigated the evolution of chronic pain in sickle cell patients (SCD) as an age‐dependent phenomenon and studied the frequency of vaso‐occlusive episode frequency, opioid use, quantitative sensory testing (QST), and biomarkers of chronic pain (CP). Methods We undertook a cross‐sectional study of the evolution of CP in SCD. A total of 72 subjects (age 15‐66) were enrolled. VOE frequency, presence of CP hydroxyurea (HU) therapy, opioid use, and laboratory parameters were collected. QST was performed, and plasma tryptase, substance P, and NGF (Nerve Growth Factor) levels were assayed. Results There was an age‐dependent increase in frequency of CP, VOEs, opioid use, and Von Frey monofilament values. CP patients had significantly higher opioid use (daily morphine equivalents) (52.8 mg vs 6.94 mg, P = .009), suggesting a correlation between opioid use and hyperalgesia. NGF levels were also significantly higher (P = .051). Our results confirm previous observations of an age‐dependent increase in the proportion of patients with CP and support the contributing role of mast cell activation and neurogenic inflammation. Conclusions This is the first study of NGF as a possible biomarker of CP in SCD. If confirmed, this could provide a diagnostic marker and therapeutic target for CP in SCD.

Considerations for Cannabis Use to Treat Pain in Sickle Cell Disease

“…These include neurogenic and neuro inflammation [26,28,56], activation of transient receptor potential vanilloid 1 (TRPV1) [26,57], peripheral nerve damage [26], peripheral and central sensitization [58,59], spinal glial activation [60,61], increased blood-brain barrier permeability [62,63], mast cell activation [56], and Purkinje cell damage in the cerebellum [64,65]. Neuroinflammation demonstrated with increased circulating substance P (SP) [66][67][68] and glial fibrillary acidic protein (GFAP) [69] and central sensitization have also been observed clinically. Dorsal horn neurons in preclinical sickle models also demonstrated higher excitability in concert with activation of signaling pathways that promote neuronal excitability [58] with increased GFAP-expressing astroglial cells [60] and microglial activation [61].…”

A bone to pick-cellular and molecular mechanisms of bone pain in sickle cell disease

“…Furthermore, local, and systemic NGF administration into healthy humans induces deep pain and hypersensitivity that can last for several days ( 88 , 89 ). Also, individuals with SCD and chronic pain also show elevated circulating levels of NGF ( 90 ). Thus, taken together, therapies that affect inflammatory cell release of NGF or inhibit NGF may be beneficial in decreasing bone pain.…”