Epidermal axonal swellings in painful and painless diabetic peripheral neuropathy

Cheung, Audrey; Podgorny, Peter; Martinez, José A.; Chan, Cynthia; Toth, Cory

doi:10.1002/mus.24351

Cited by 28 publications

(18 citation statements)

References 41 publications

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“…[37] This is because there is controversy as to whether specific features of small fibre pathology in skin biopsies[38,39] may be related to painful neuropathy. [17,18,40,41]…”

Section: Discussionmentioning

confidence: 99%

Greater small nerve fibre damage in the skin and cornea of type 1 diabetic patients with painful compared to painless diabetic neuropathy

Ferdousi

Azmi

Kalteniece

et al. 2021

Euro J of Neurology

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Background and aim Damage to small nociceptive fibres may contribute to painful diabetic neuropathy. We aimed to compare large and small nerve fibre measurements together with skin biopsy and corneal confocal microscopy in patients with type 1 diabetes and painful or painless diabetic neuropathy. Methods We have assessed the McGill pain questionnaire, neuropathy disability score, vibration perception threshold, warm and cold sensation thresholds, electrophysiology, corneal confocal microscopy and skin biopsy in participants with type 1 diabetes and painful (n = 41) or painless (n = 50) diabetic neuropathy and control subjects (n = 50). Results The duration of diabetes, body mass index, glycated haemoglobin (HbA1c), blood pressure and lipid profile did not differ between subjects with painful and painless neuropathy. Neuropathy disability score and vibration perception threshold were higher and sural nerve conduction velocity was lower, but sural nerve amplitude, peroneal nerve amplitude and conduction velocity and cold and warm sensation thresholds did not differ between patients with painful compared to painless diabetic neuropathy. However, intraepidermal nerve fibre density, corneal nerve fibre density, corneal nerve branch density and corneal nerve fibre length were significantly lower in subjects with painful compared to painless diabetic neuropathy. Conclusions There is evidence of more severe neuropathy, particularly small fibre damage in the skin and cornea, of patients with painful compared to painless diabetic neuropathy.

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“…[37] This is because there is controversy as to whether specific features of small fibre pathology in skin biopsies[38,39] may be related to painful neuropathy. [17,18,40,41]…”

Section: Discussionmentioning

confidence: 99%

Greater small nerve fibre damage in the skin and cornea of type 1 diabetic patients with painful compared to painless diabetic neuropathy

Ferdousi

Azmi

Kalteniece

et al. 2021

Euro J of Neurology

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“…However, Scheytt et al found no relationship between pain and GAP-43 reactivity in subjects with peripheral neuropathies of varying etiologies [52]. There are contradictory findings in studies investigating other IENF markers to differentiate painful- from painless-DPN including IENF length [50•, 53] and axonal swellings, which are measures of axonal degeneration [49, 54]. Levels within the skin of the neurotrophin nerve growth factor (NGF) were increased in patients with DPN and sensory symptoms, including pain, compared to painless-DPN [55].…”

Section: Cardiovascular Autonomic Neuropathymentioning

confidence: 99%

Painful and Painless Diabetic Neuropathies: What Is the Difference?

et al. 2019

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Purpose of Review The prevalence of diabetes mellitus and its chronic complications are increasing to epidemic proportions. This will unfortunately result in massive increases in diabetic distal symmetrical polyneuropathy (DPN) and its troublesome sequelae, including disabling neuropathic pain (painful-DPN), which affects around 25% of patients with diabetes. Why these patients develop neuropathic pain, while others with a similar degree of neuropathy do not, is not clearly understood. This review will look at recent advances that may shed some light on the differences between painful and painless-DPN. Recent Findings Gender, clinical pain phenotyping, serum biomarkers, brain imaging, genetics, and skin biopsy findings have been reported to differentiate painful- from painless-DPN. Summary Painful-DPN seems to be associated with female gender and small fiber dysfunction. Moreover, recent brain imaging studies have found neuropathic pain signatures within the central nervous system; however, whether this is the cause or effect of the pain is yet to be determined. Further research is urgently required to develop our understanding of the pathogenesis of pain in DPN in order to develop new and effective mechanistic treatments for painful-DPN.

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“…The main symptoms of diabetic neuropathy are tingling and numbness in the distal extremities sometimes accompanied by burning pain (Argoff et al 2006). Animal and human histochemical studies indicate that diabetes can cause dieback of PNS epidermal endings (Sorensen et al 2006; Cheng et al 2013; Cheung et al 2015; Ebenezer and Polydefkis 2014), an outcome that may not be related to pain (Sorensen et al 2006). Also, in studies where diabetes is modeled in animals, the development of ectopic activity in DRG neurons (Khan et al 2002; Serra et al 2012) has been demonstrated.…”

Section: 8 Ampk: Diabetic Neuropathy Prevention and Treatmentmentioning

confidence: 99%

Targeting AMPK for the Alleviation of Pathological Pain

Asiedu

Dussor

Price

2016

Experientia Supplementum

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Chronic pain is a major clinical problem that is poorly treated with available therapeutics. Adenosine monophosphate-activated protein kinase (AMPK) has recently emerged as a novel target for the treatment of pain with the exciting potential for disease modification. AMPK activators inhibit signaling pathways that are known to promote changes in the function and phenotype of peripheral nociceptive neurons and promote chronic pain. AMPK activators also reduce the excitability of these cells suggesting that AMPK activators may be efficacious for the treatment of chronic pain disorders, like neuropathic pain, where changes in the excitability of nociceptors is thought to be an underlying cause. In agreement with this, AMPK activators have now been shown to alleviate pain in a broad variety of preclinical pain models indicating that this mechanism might be engaged for the treatment of many types of pain in the clinic. A key feature of the effect of AMPK activators in these models is that they can lead to a long-lasting reversal of pain hypersensitivity even long after treatment cessation, indicative of disease modification. Here, we review the evidence supporting AMPK as a novel pain target pointing out opportunities for further discovery that are likely to have an impact on drug discovery efforts centered around potent and specific allosteric activators of AMPK for chronic pain treatment.

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Epidermal axonal swellings in painful and painless diabetic peripheral neuropathy

Abstract: There was no clinical relationship to pain or clinical neuropathy severity for axonal swellings in DPN.

Cited by 28 publications

References 41 publications

Greater small nerve fibre damage in the skin and cornea of type 1 diabetic patients with painful compared to painless diabetic neuropathy

Greater small nerve fibre damage in the skin and cornea of type 1 diabetic patients with painful compared to painless diabetic neuropathy

Painful and Painless Diabetic Neuropathies: What Is the Difference?

Targeting AMPK for the Alleviation of Pathological Pain

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