Neurochemical Research

, Volume 37, Issue 10, pp 2065–2075 | Cite as

Role of Oxidative Stress and Ca2+ Signaling on Molecular Pathways of Neuropathic Pain in Diabetes: Focus on TRP Channels

  • Mustafa NazıroğluEmail author
  • Döndü Merve Dikici
  • Şeyda Dursun


Diabetes mellitus, a debilitating chronic disease, affects ~100 million people. Peripheral neuropathy is one of the most common early complications of diabetes in ~66 % of these patients. Altered Ca2+ handling and Ca2+ signaling were detected in a huge variety of preparations isolated from animals with experimentally induced type 1 and 2 diabetes as well as patients suffering from the disease. We reviewed the role of Ca2+ signaling through cation channels and oxidative stress on diabetic neuropathic pain in sensory neurons. The pathogenesis of diabetic neuropathy involves the polyol pathway, advanced glycation end products, oxidative stress, protein kinase C activation, neurotrophism, and hypoxia. Experimental studies with respect to oxidative stress and Ca2+ signaling, inhibitor roles of antioxidants in diabetic neuropathic pain are also summarized in the review. We hypothesize that deficits in insulin, triggers alterations of sensory neurone phenotype that are critical for the development of abnormal Ca2+ homeostasis and oxidative stress and associated mitochondrial dysfunction. The transient receptor potential channels are a large family of proteins with six main subfamilies. The sheer number of different TRPs with distinct functions supports the statement that these channels are involved in a wide range of processes ranging in diabetic neuropathic pain and it seems that the TRPC, TRPM and TRPV groups are mostly responsible from diabetic neuropathic pain. In conclusion, the accumulating evidence implicating Ca2+ dysregulation and over production of oxidative stress products in diabetic neuropathic pains, along with recent advances in understanding of genetic variations in cation channels such as TRP channels, makes modulation of neuronal Ca2+ handling an increasingly viable approach for therapeutic interventions against the painful and degenerative aspects of many diabetic neuropathies.


Calcium ion Diabetes Sensory neurons Pain Oxidative stress Transient receptor potential channels Mitochondria 





Human embryonic kidney


Insulin growth factor


Nerve growth factor




Nitric oxide


Protein kinase A


Protein kinase C


Advanced glycation end-products


Reactive oxygen species


Sarcoendoplasmic reticulum Ca2+-ATPase




Tricarboxylic acid


Transient receptor potential


Transient receptor potential vanilloid 1


Voltage-dependent Ca2+ channels



There is no financial support and conflict interest in the current study.


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Mustafa Nazıroğlu
    • 1
    Email author
  • Döndü Merve Dikici
    • 1
  • Şeyda Dursun
    • 1
  1. 1.Department of Biophysics, Medical FacultySüleyman Demirel UniversityIspartaTurkey

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