Challenges of neuropathic pain: focus on diabetic neuropathy

Abstract

Neuropathic pain is a frequent condition caused by a lesion or disease of the central or peripheral somatosensory nervous system. A frequent cause of peripheral neuropathic pain is diabetic neuropathy. Its complex pathophysiology is not yet fully elucidated, which contributes to underassessment and undertreatment. A mechanism-based treatment of painful diabetic neuropathy is challenging but phenotype-based stratification might be a way to develop individualized therapeutic concepts. Our goal is to review current knowledge of the pathophysiology of peripheral neuropathic pain, particularly painful diabetic neuropathy. We discuss state-of-the-art clinical assessment, validity of diagnostic and screening tools, and recommendations for the management of diabetic neuropathic pain including approaches towards personalized pain management. We also propose a research agenda for translational research including patient stratification for clinical trials and improved preclinical models in relation to current knowledge of underlying mechanisms.

Understanding Diabetic Neuropathy: Focus on Oxidative Stress

“…The current approaches to managing diabetic neuropathy focus on improving glycaemic control, mainly in type I diabetic patients, and lifestyle modifications, mainly in type II diabetic patients [35,69]. Although diabetic neuropathy is the strongest predictor of mortality in type II diabetes, it remains the only microvascular complication of diabetes without a specific treatment owing to our lack of basic understanding of this disease.…”

“…Increased glucose levels in diabetes affect primarily those cells that have a limited capacity to regulate their glucose intake, including vascular cells, Schwann cells, and neurons of the peripheral and central nervous systems [ 35 , 36 ]. It is unclear whether high glucose triggers axonal degeneration by promoting intrinsic programmes within axons [ 36 – 38 ], nor is whether peripheral axons or their associated Schwann cells, the first target.…”

“…In addition, lowing haemoglobin A1c in type II diabetic patients has little effect on diabetic neuropathy [ 64 ], whereas a greater improvement has been observed in type I diabetic patients after 18 months of glycemic control [ 48 ]. Collectively, it suggests that hyperglycaemia is not the prime driving cause of all complications [ 35 , 65 ], and mechanisms underlying diabetic neuropathy in type I and type II diabetes could be fundamentally different [ 47 ].…”

Advances in the understanding and treatment of pain and headache

“…Secondly, Rosenberger et al (2020) review our current knowledge on the pathophysiology of peripheral neuropathic pain, particularly painful diabetic neuropathy. Neuropathic pain is a frequent condition caused by a lesion or disease of the central or peripheral somatosensory nervous system, and diabetic neuropathy is a frequent cause of peripheral neuropathic pain.…”

“…Neuropathic pain is a frequent condition caused by a lesion or disease of the central or peripheral somatosensory nervous system, and diabetic neuropathy is a frequent cause of peripheral neuropathic pain. Rosenberger et al (2020) discuss the state-of-the-art of clinical assessment, validity of diagnostic, screening tools, and recommendations for the management of diabetic neuropathic pain patients, including personalized pain management. They also propose a research agenda for translational research, including patient stratification for clinical trials, and improved preclinical models based on our current understanding of the underlying mechanisms.…”