title: Painful Diabetic Neuropathy: Prevention or Suppression?
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 nonspecific 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 posttranslational 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 posttranslational 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.
authors.affiliation: School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, United States. Electronic address: slobodan.todorovic@ucdenver.edu.
authors.forename: S M
authors.initials: SM
authors.lastname: Todorovic
mesh_terms: D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D020747:Calcium Channels, T-Type / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000150:complications*; D006801:Humans; D006930:Hyperalgesia / Q000209:etiology / Q000517:prevention & control / Q000628:therapy; D010146:Pain / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D017288:Pain Threshold / Q000187:drug effects; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D050916:TRPV Cation Channels / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000700:Analgesics; D020747:Calcium Channels, T-Type; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D005680:gamma-Aminobutyric Acid
keywords: Allodynia; Calcium; Diabetes; GABA; Hyperalgesia; Nociceptors; T-type channels; TRPV1