Targeting pain at its source in sickle cell disease

Kanika Gupta, Om Jahagirdar, Kalpna Gupta

Research output: Contribution to journalReview article

6 Scopus citations

Abstract

Sickle cell disease (SCD) is a genetic disorder associated with hemolytic anemia, end-organ damage, reduced survival, and pain. One of the unique features of SCD is recurrent and unpredictable episodes of acute pain due to vasoocclusive crisis requiring hospitalization. Additionally, patients with SCD often develop chronic persistent pain. Currently, sickle cell pain is treated with opioids, an approach limited by adverse effects. Because pain can start at infancy and continue throughout life, preventing the genesis of pain may be relatively better than treating the pain once it has been evoked. Therefore, we provide insights into the cellular and molecular mechanisms of sickle cell pain that contribute to the activation of the somatosensory system in the peripheral and central nervous systems. These mechanisms include mast cell activation and neurogenic inflammation, peripheral nociceptor sensitization, mal-adaptation of spinal signals, central sensitization, and modulation of neural circuits in the brain. In this review, we describe potential preventive/therapeutic targets and their targeting with novel pharmacologic and/or integrative approaches to ameliorate sickle cell pain.

Original languageEnglish (US)
Pages (from-to)R104-R112,
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume315
Issue number1
DOIs
StatePublished - Jul 25 2018

Keywords

  • Analgesia
  • Mast cell
  • Neurogenic inflammation
  • Opioid
  • Pain
  • Sickle cell disease
  • Substance p
  • Vasoocclusive crises

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