Diabetic neuropathic pain: Physiopathology and treatment

Abstract

Diabetic neuropathy is a common complication of both type 1 and type 2 diabetes, which affects over 90% of the diabetic patients. Although pain is one of the main symptoms of diabetic neuropathy, its pathophysiological mechanisms are not yet fully known. It is widely accepted that the toxic effects of hyperglycemia play an important role in the development of this complication, but several other hypotheses have been postulated. The management of diabetic neuropathic pain consists basically in excluding other causes of painful peripheral neuropathy, improving glycemic control as a prophylactic therapy and using medications to alleviate pain. First line drugs for pain relief include anticonvulsants, such as pregabalin and gabapentin and antidepressants, especially those that act to inhibit the reuptake of serotonin and noradrenaline. In addition, there is experimental and clinical evidence that opioids can be helpful in pain control, mainly if associated with first line drugs. Other agents, including for topical application, such as capsaicin cream and lidocaine patches, have also been proposed to be useful as adjuvants in the control of diabetic neuropathic pain, but the clinical evidence is insufficient to support their use. In conclusion, a better understanding of the mechanisms underlying diabetic neuropathic pain will contribute to the search of new therapies, but also to the improvement of the guidelines to optimize pain control with the drugs currently available.

Nanoparticle-encapsulated emodin decreases diabetic neuropathic pain probably via a mechanism involving P2X3 receptor in the dorsal root ganglia

“…Diabetic neuropathic pain (DNP) is the most common complication of T2DM. DNP leads to dysfunction in the dorsal root ganglia (DRG) [2][3][4]. Toxicity of hyperglycaemia is associated with local metabolic changes in T2DM [3,5].…”

“…Long-standing hyperglycemia destroys the homeostasis of peripheral tissues and causes peripheral nerve injury [6]. DNP includes spontaneous pain, allodynia (pain to normally innocuous stimuli), and hyperalgesia (increased pain perception to noxious stimuli) [3,4,7,8]. As a chronic peripheral neuropathy, DNP has a substantial impact on the quality of life of diabetic patients.…”

PGE2, Kidney Disease, and Cardiovascular Risk

“…A wide range of symptoms arise as a result of the diabetic injury, ranging from an exaggerated perception of sensory stimuli to spontaneous paresthesias and pain, features of both allodynia and hyperalgesia. Recently published studies provide an elaborate review of the pathophysiology underlying the neuropathic pain 71 as well as the detailed mechanisms triggered by hyperglycemia leading to nerve injury. 72 Although hyperglycemia is central to the pathogenesis of diabetic neuropathy, a number of metabolic and vascular factors are involved.…”

LncRNA uc.48+ is involved in diabetic neuropathic pain mediated by the P2X3 receptor in the dorsal root ganglia

“…DM is a major cause of peripheral neuropathy. Diabetic neuropathic pain (DNP) is a direct consequence of abnormalities in the dorsal root ganglia (DRG) [3,5,6]. Hyperglycemia destroys the homeostasis of peripheral tissues by damaging nerve fibers [7].…”