Painful diabetic peripheral neuropathy: Role of oxidative stress and central sensitisation

Abstract

Aims: Diabetic peripheral neuropathy (DPN) occurs in about half of people with diabetes, of whom a quarter may develop chronic pain. Pain may remain for years yet be difficult to treat because the underlying mechanisms remain unclear.There is consensus that processing excessive glucose leads to oxidative stress, interfering with normal metabolism. In this narrative review, we argue that oxidative stress may also contribute to pain. Methods: We reviewed literature in PubMed published between January 2005 and August 2021. Results and conclusions: In diabetes, hyperglycaemia and associated production of reactive species can directly increase pain signalling and activate sensory neurons; or the effects can be indirect, mediated by mitochondrial damage and enhanced inflammation. Furthermore, pain processing in the central nervous system is compromised in painful DPN. This is implicated in central sensitisation and dysfunctional pain modulation. However, central pain modulatory function is understudied in diabetes. Future research is required to clarify whether central sensitisation and/or disturbances in central pain modulation contribute to painful DPN. Positive results would facilitate early detection and future treatment.

Diyabetik Periferik Polinöropatili Hastalarda İnterlökin-23R Gen Polimofizmleri

“…Many theories have been suggested in the pathogenesis of DPN (22). One of them is oxidative stress and related inflammation.…”

Efficacy and safety of Mudan granules for painful diabetic peripheral neuropathy

“…The pathogenesis of PDPN is still unclear, and scholars hold the view that it is multifactorial. [ 24 ] Lower limb symptoms are more common than the upper limb, the disease is stabbing pain, burning pain, and drilling pain. Sometimes, severe pain such as amputation pain was aggravated day and night, which could cause foot ulcers, neuroarthritis, and life-threatening.…”

“…The pathogenesis of PDPN is still unclear, and scholars hold the view that it is multifactorial [24] . Lower limb symptoms are more common than the upper limb, the disease is stabbing pain, burning pain, and drilling pain.…”

Alpha-Lipoic Acid as an Antioxidant Strategy for Managing Neuropathic Pain

“…Either by initiating or maintaining the pathophysiological processes that lead to NP, the imbalance of ROS and RNS has been proposed to be central in the chain of events resulting in the neuropathic state. In fact, the nitro-oxidative stress component was associated with the development of different models of painful neuropathies, such as diabetic neuropathy [ 22 , 23 ], chemotherapy-induced neuropathy [ 24 ], peripheral nerve injury-induced neuropathic pain [ 25 ], and Charcot-Marie-Tooth [ 26 ]. Moreover, increased levels of oxidative stress markers were found in subacute post-stroke patients affected by NP [ 27 ].…”

“…This state also contributes to nociceptive signaling by activating receptors and channels such as TRPV1, ASIC, and P2X [ 40 ]. Finally, mitochondrial dysfunction leads to increased production of superoxide and peroxynitrite, which cause damage to proteins, lipids, and nucleic acids, hence boosting nitro-oxidative stress and contributing to neuroinflammation [ 22 ].…”