Painful Diabetic Neuropathy

Abstract

Pain-sensing sensory neurons (nociceptors) of the dorsal root ganglia (DRG) and dorsal horn (DH) can become sensitized (hyperexcitable) in response to pathological conditions such as diabetes, which in turn may lead to the development of painful peripheral diabetic neuropathy (PDN). Because of incomplete knowledge about the mechanisms underlying painful PDN, current treatment for painful PDN has been limited to somewhat non-specific systemic drugs that have significant side effects or potential for abuse. Recent studies have established that several ion channels in DRG and DH neurons are dysregulated and make a previously unrecognized contribution to sensitization of pain responses by enhancing excitability of nociceptors in animal models of Type 1 and Type 2 PDN. Furthermore, it has been reported that targeting post-translational modification of nociceptive ion channels such as glycosylation and methylglyoxal metabolism can completely reverse mechanical and thermal hyperalgesia in diabetic animals with PDN in vivo. Understanding details of post-translational regulation of nociceptive channel activity may facilitate development of novel therapies for treatment of painful PDN. We argue that pharmacological targeting of the specific pathogenic mechanism rather than of the channel per se may cause fewer side effects and reduce the potential for drug abuse in patients with diabetes.

Suppressing PKC-dependent membrane P2X3 receptor upregulation in dorsal root ganglia mediated electroacupuncture analgesia in rat painful diabetic neuropathy

“…Although current medication for PDN is unsatisfactory or has significant side effects [3], the potential value of electroacupuncture, which is widely used in pain management nowadays, in treating PDN has begun to attract attention [20,21]. Accumulating evidence demonstrated that electroacupuncture (EA) at low frequency could effectively attenuate neuropathic pain [22][23][24][25].…”

“…Patients with PDN often experience aberrant pain sensation, including spontaneous pain, hyperalgesia, and allodynia that seriously affect their life quality [2]. Studies show that several ion channels and receptors in dorsal root ganglia (DRG) are dysregulated in PDN, which make a contribution to sensitization of pain responses by enhancing excitability of nociceptor [3][4][5][6].…”

The H-Reflex as a Biomarker for Spinal Disinhibition in Painful Diabetic Neuropathy

“…For example, patients with diabetic neuropathy whose pain is driven by spinal disinhibition will demonstrate impaired RDD and may respond preferentially to anti-neuropathic pain medications that overcome disinhibition such as SNRI’s [115, 114]. Conversely patients with pain driven predominantly by peripheral mechanisms such as nociceptor hyperexcitability might show greater therapeutic response to drugs acting on ion channels of primary afferents [128]. Using RDD as a simple to employ biomarker may also be useful to select patients likely to be most responsive to a given therapy undergoing clinical trial based on the primary mechanism of pain generation.…”

Fecal microbiota transplantation relieve painful diabetic neuropathy

“…DN is the most frequent complication of DM and finally contributes to the increase of morbidity and mortality. [1] It includes peripheral neuropathy, single neuropathy, and autonomic neuropathy, which mainly affects the distal end of the lower extremities, often characterized by loss of sensation, pain, numbness, gait disorder even amputation. Despite a high prevalence rate, the pathological mechanism of DN remains unknown.…”

“…[2,3] Early detection of DN can only be achieved by assessing the nerve fibers, and current treatment of DN is limited to certain non-specific drugs with side effects and possibility of abuse. [1,4] DN has a significant impact on the health-related quality of life.…”