TNF-alpha blocking in diabetic painful neuropathy is cool

In a new paper on the Beneficial effect of TNF-α inhibition on diabetic peripheral neuropathy, in the Journal of Neuroinflammation 2013, 10:69 doi:10.1186/1742-2094-10-69, the authors present a whole bunch of data proving that TNF-alpha is one of the bad guys in the genesis of neuropathic pain in diabetes.

Rita Levi Montalcini with TNF-alpha

Rita Levi Montalcini with TNF-alpha

They point out that Tumor necrosis factor-α (TNF-α) has been shown to play a central role in the pathogenesis of DPN and that elevated levels of TNF-α and soluble TNF-α receptors (sTNFR1 and sTNFR2) have been reported in the serum of patients with Diabetic peripheral neuropathy (DPN). TNF-alpha has already be pointed out to be a destructive molecule by Rita Levi-Montalcini (here ar her 10ost birthday)

Now interestingly PEA is a clear TNF-alpha blocker, and a natural one without side effects…..

We quote a part of their paper:

Previous studies have also shown that the expression of TNF-α in the blood of DPN patients and rat DPN model is elevated. TNF-α is an important immune cytokine involved in the developmental process of many inflammatory, infectious, and autoimmune diseases and functions to kill or inhibit tumor cells, increase the phagocytic activity of neutrophils, and stimulate the production of other cytokines [9]. The pathological changes of DPN are characterized by axonal degeneration in unmyelinated fibers, while demyelination and diffused shrinkage in myelin nerve fibers [20,21]. The immune response, in which self-antigen component gets exposed, is the main reason leading to demyelination in case of DPN. T-cells activated by these antigens produce various cytokines, including TNF-α, which has a potential positive feed-back cycle to further raise its own immune response to mediate the inflammatory reaction [9]. It has been found that TNF-α expression leads to the oligodendrocyte toxicity and demyelination. It stimulates monocytes and endothelial cells to secrete IL-1β and IL-6 and other inflammatory factors to amplify or enhance its effect indirectly[22]. Furthermore, TNF-α inhibits the nitric oxide synthase (NOS) activity in vascular endothelial cell, resulting in a decrease of NO-induced vasodilatation. It has been shown to promote the expression of several growth factors and cell adhesion molecules, resulting in endothelial dysfunction and pathogenesis including stenosis, hemodynamic abnormalities, decreased perfusion, and neurotrophic blood vessels damage [23,24].

To further confirm the role of TNF-α in the DPN pathogenesis, in the present study, we applied subcutaneous injection of a TNF-α receptor-antibody fusion protein (rhTNFR:Fc) to the DPN-induced rats in order to inhibit TNF-α. The results showed that rhTNFR:Fc treatment in rats with DPN significantly increased NCV and MNCV values, particularly in high-dose group indicating that rhTNFR:Fc effectively delayed the progress of the DPN in rats with DPN. This was further confirmed by histological and TEM ultrastructure examination of the sciatic nerve. The sciatic nerve of DPN-induced rats showed the typical pathological features including thinning and destruction of the myelin sheath and disorganization of the lamellar structures. Inhibition of TNF-α with rhTNFR:Fc, however, resulted in a marked improvement of sciatic nerve and its component’s morphology. This beneficial effect of targeting TNF-α is in agreement with a recent study that pharmacological inhibition of TNF-α by etanercept, a TNF-α antagonist, blocks behavioral signs of diabetic neuropathic pain [25].

TNF-alpha blockade makes sense in Diabetic Polyneuropathy. The best TNF-blocker we have access to for the patient is PEA. PEA is available as the supplement PeaPure and to date no relevant side effects have been documented.

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