Epidermal nerve fiber quantification in the assessment of diabetic neuropathy

Beiswenger, Kristina K.; Calcutt, Nigel A.; Mizisin, Andrew P.

doi:10.1016/j.acthis.2007.12.004

Cited by 109 publications

(93 citation statements)

References 69 publications

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“…These structural changes are accompanied by increased expression of neuropeptides substance P SP and calcitonin-gene-related peptides CGRP in the skin [12]. Concomitantly, skin in "ERK sickle mice is signiicantly thinner with a comparatively thinner epidermis, similar to that observed in other murine models of pain such as diabetes [41]. These structural and neurochemical alterations in association with well-known inlammatory milieu may likely activate nociceptors on the peripheral nerve terminals as demonstrated by activation of transient receptor potential cation channel subfamily V member 1 TRPV1 in the skin of "ERK sickle mice [11].…”

Section: Peripheral and Central Mechanisms Of Pain In Scdsupporting

confidence: 52%

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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Section: Peripheral and Central Mechanisms Of Pain In Scdsupporting

confidence: 52%

Mechanisms of Pain in Sickle Cell Disease

Aich¹,

Beitz²,

Gupta³

2016

Sickle Cell Disease - Pain and Common Chronic Complications

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“…Tissue was processed to paraffin blocks, cut as 6-μm sections, and immunostained using an antibody to PGP 9.5 (cat. 7863-0504; 1:1000, AbD Serotec); the number of immunoreactive IENF profiles was quantified under blinded conditions by light microscopy and normalized to length of the dermal/ epidermal junction (86).…”

Section: Methodsmentioning

confidence: 99%

Selective antagonism of muscarinic receptors is neuroprotective in peripheral neuropathy

Calcutt¹,

Smith²,

Frizzi³

et al. 2017

Journal of Clinical Investigation

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“…Diabetes-induced changes in C fibers lead to the development of small-fiber neuropathy, which often produces positive (painful) symptoms: allodynia and hyperesthesias. Progressive neurodegeneration may spontaneously resolve the neuropathic pain, but decreased response thresholds (Lennertz et al, 2011) and loss of epidermal innervation of C fibers in the feet (Beiswenger et al, 2008) can contribute to negative neuropathic symptoms such as thermal hypoalgesia. Likewise, degeneration of A␤ fibers leads to a loss of vibration and tactile sensation (Lennertz et al, 2011) with axon-myelin separation (Powell and Myers, 1983;Myers and Powell, 1984;Love et al, 1986) and eventual segmental demyelination in long-term DPN (Zochodne, 2007).…”

Section: Dpnmentioning

confidence: 99%