Sensitization of nociceptive spinal neurons contributes to pain in a transgenic model of sickle cell disease

Giuseppe Cataldo, Sugandha Rajput, Kalpna Gupta, Donald A Simone

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Abstract

Chronic pain is a major characteristic feature of sickle cell disease (SCD). The refractory nature of pain and the development of chronic pain syndromes in many patients with SCD suggest that central neural mechanisms contribute to pain in this disease. We used HbSS-BERK sickle mice, which show chronic features of pain similar to those observed in SCD, and determined whether sensitization of nociceptive neurons in the spinal cord contributes to pain and hyperalgesia in SCD. Electrophysiological recordings of action potential activity were obtained from single identified dorsal horn neurons of the spinal cord in anesthetized mice. Compared with control HbAA-BERK mice, nociceptive dorsal horn neurons in sickle mice exhibited enhanced excitability as evidenced by enlarged receptive fields, increased rate of spontaneous activity, lower mechanical thresholds, enhanced responses to mechanical stimuli, and prolonged afterdischarges following mechanical stimulation. These changes were accompanied by increased phosphorylation of mitogen-activated protein kinases (MAPKs) in the spinal cord that are known to contribute to neuronal hyperexcitability, including c-Jun N-terminal kinase (JNK), p44/p42 extracellular signaling-regulated kinase (ERK), and p38. These findings demonstrate that central sensitization contributes to pain in SCD.

Original languageEnglish (US)
Pages (from-to)722-730
Number of pages9
JournalPain
Volume156
Issue number4
DOIs
StatePublished - Apr 1 2015

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Nociceptors
Sickle Cell Anemia
Pain
Chronic Pain
Posterior Horn Cells
Spinal Cord
Central Nervous System Sensitization
Intractable Pain
JNK Mitogen-Activated Protein Kinases
Hyperalgesia
Mitogen-Activated Protein Kinases
Action Potentials
Phosphotransferases
Phosphorylation

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Sensitization of nociceptive spinal neurons contributes to pain in a transgenic model of sickle cell disease. / Cataldo, Giuseppe; Rajput, Sugandha; Gupta, Kalpna; Simone, Donald A.

In: Pain, Vol. 156, No. 4, 01.04.2015, p. 722-730.

Research output: Contribution to journalArticle

Cataldo, Giuseppe ; Rajput, Sugandha ; Gupta, Kalpna ; Simone, Donald A. / Sensitization of nociceptive spinal neurons contributes to pain in a transgenic model of sickle cell disease. In: Pain. 2015 ; Vol. 156, No. 4. pp. 722-730.
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