Sickle cell disease in mice is associated with sensitization of sensory nerve fibers

Kenyon, Nicholas J.; Wang, Li; Spornick, Nicholas; Khaibullina, Alfia; Almeida, Luis E.F.; Cheng, Yao I.; Wang, Jichuan; Guptill, Virginia; Finkel, Julia C.; Quezado, Zenaide M.N.

doi:10.1177/1535370214544275

Cited by 33 publications

(38 citation statements)

References 45 publications

(122 reference statements)

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“…[4-9] The main objectives and outcomes of these studies are described in Table 1. In summary, all studies provided evidence that abnormalities exist in the peripheral and/or central nervous system that likely contribute to the pathobiology of SCD pain in a murine SCD model.…”

Section: Resultsmentioning

confidence: 99%

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

Brandow

Farley

Panepinto

2015

Pediatric Blood & Cancer

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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.

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Section: Resultsmentioning

confidence: 99%

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

Brandow

Farley

Panepinto

2015

Pediatric Blood & Cancer

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“…These animals display thermal, mechanical, and muscle hyperalgesia and sensitization of somatosensory fibers(Cain et al, 2012; Garrison et al, 2012; Hillery et al, 2011; Kenyon et al, 2015; Kohli et al, 2010; Vincent et al, 2013). Interestingly, this mechanical and thermal hyperalgesia is accentuated by hypoxia and reoxygenation, which suggest that the altered nocifensive phenotype in SCD mice could partially result from recurrent ischemia/reperfusion injury associated with vaso-occlusion(Cain et al, 2012; Hebbel, 2014).…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine ameliorates nocifensive behavior in humanized sickle cell mice

Calhoun

Wang

Almeida

et al. 2015

European Journal of Pharmacology

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Patients with sickle cell disease (SCD) can have recurrent episodes of vaso-occlusive crises, which are associated with severe pain. While opioids are the mainstay of analgesic therapy, in some patients, increasing opioid use results in continued and increasing pain. Many believe that this phenomenon results from opioid-induced tolerance or hyperalgesia or that SCD pain involves non-opioid-responsive mechanisms. Dexmedetomidine, a specific α2-adrenoreceptor agonist, which has sedative and analgesic properties, reduces opioid requirements, and can facilitate opioid withdrawal in clinical settings. We hypothesized that dexmedetomidine would ameliorate the nociception phenotype of SCD mice. Townes and BERK SCD mice, strains known to have altered nociception phenotypes, were used in a crossover preclinical trial that measured nocifensive behavior before and after treatment with dexmedetomidine or vehicle. In a linear dose-effect relationship, over 60-min, dexmedetomidine, compared with vehicle, significantly increased hot plate latency in Townes and BERK mice (P≤0.006). In sickling, but not control mice, dexmedetomidine improved grip force, an indicator of muscle pain (P=0.002). As expected, dexmedetomidine had a sedative effect in sickling and control mice as it decreased wakefulness scores compared with vehicle (all P<0.001). Interestingly, the effects of dexmedetomidine on hot plate latency and wakefulness scores were different in sickling and control mice, i.e., dexmedetomidine-related increases in hotplate latency and decreases in wakefulness scores were significantly smaller in Townes sickling compared to control mice. In conclusion, these findings of beneficial effects of dexmedetomidine on the nociception phenotype in SCD mice might support the conduct of studies of dexmedetomidine in SCD patients.

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“…Israel which employs cold temperature to the skin via a peltier-based thermode [7,8] Paw withdrawal latency and frequency in response to static heat stimuli in "ERK mice [9, 11 13] and in Townes mice [14], Lei et al, 2016, under review] Cold hyperalgesia QST using Thermal Sensory "nalyzer Medoc:…”

Section: Subjects With Scd Transgenic Mice Expressing Sickle Hemoglobinmentioning

confidence: 99%

Mechanisms of Pain in Sickle Cell Disease

Aich¹,

Beitz²,

Gupta³

2016

Sickle Cell Disease - Pain and Common Chronic Complications

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Pain is one of the most common features of sickle cell disease SCD lacking efective therapy. Pain in SCD is relatively more complicated than other conditions associated with pain requiring understanding of the pathobiology of pain speciic to SCD. The characterization of pain to deine the diverse modalities of nociception in SCD is currently under progress via human studies accompanied by transgenic mouse models of SCD. Sickle pathobiology characterized by oxidative stress, inlammation and vascular dysfunction contributes to both peripheral and central nociceptive sensitization via mast cell activation in the periphery, and reactive oxygen species and glial activation and endoplasmic reticulum stress in the spinal cord among other efectors. These efects are mediated via several cellular receptors, which can be targeted to produce positive therapeutic outcomes. In this chapter, we will discuss the present understanding of molecular mechanisms of SCD pain and outline the mechanism-based translational potential of novel actionable targets to treat SCD pain.Keywords: pain, sickle cell disease, neurogenic inlammation, substance P, mast cell . IntroductionPain is a hallmark feature of sickle cell disease SCD , which can start in infancy, leading to hospitalization, reduced survival and poor quality of life. Pain in SCD is unique because of unpredictable and recurrent episodes of acute pain due to vaso-occlusive crises VOC , in addition to chronic pain experienced by a majority of adult patients on a daily basis [1]. Treatment choices remain limited to opioids, which impose liabilities of their own including constipation, mast cell activation, fear of addiction and respiratory depression [2]. Moreover, signiicantly larger doses of opioids are required to treat pain in SCD as compared to other acute and chronic pain conditions [1]. Pain can be lifelong in SCD and may therefore inluence © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.cognitive function and lead to depression and anxiety, which can in turn promote the perception of pain [1].Treatment of chronic pain remains unsatisfactory overall, perhaps due to the diverse pathobiology in diferent diseases. Therefore, it is critical to understand the mechanisms speciic to the genesis of sickle pain to develop targeted therapies. Vascular dysfunction, inlammation, ischemia/reperfusion injury and oxidative stress in the wake of VOC can each evoke activation of the nociceptive nerve ibers leading to acute pain. On the other hand, con...

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Sickle cell disease in mice is associated with sensitization of sensory nerve fibers

Cited by 33 publications

References 45 publications

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

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

Dexmedetomidine ameliorates nocifensive behavior in humanized sickle cell mice

Mechanisms of Pain in Sickle Cell Disease

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