TY - JOUR
T1 - Channelopathies, painful neuropathy, and diabetes: which way does the causal arrow point?
AU - Hoeijmakers, Janneke G. J.
AU - Faber, Catharina G.
AU - Merkies, Ingemar S. J.
AU - Waxman, Stephen G.
PY - 2014/10
Y1 - 2014/10
N2 - Diabetes mellitus, a major global health problem, is commonly associated with painful peripheral neuropathy, which can substantially erode quality of life. Despite its clinical importance, the pathophysiology of painful diabetic neuropathy is incompletely understood. It has traditionally been thought that diabetes may cause neuropathy in patients with appropriate genetic makeup. Here, we propose a hypothesis whereby painful neuropathy is not a complication of diabetes, but rather occurs as a result of mutations that, in parallel, confer vulnerability to injury in pancreatic beta cells and pain-signaling dorsal root ganglion (DRG) neurons. We suggest that mutations of sodium channel Na(V)1.7, which is present in both cell types, may increase susceptibility for development of diabetes via beta cell injury and produce painful neuropathy via a distinct effect on DRG neurons.
AB - Diabetes mellitus, a major global health problem, is commonly associated with painful peripheral neuropathy, which can substantially erode quality of life. Despite its clinical importance, the pathophysiology of painful diabetic neuropathy is incompletely understood. It has traditionally been thought that diabetes may cause neuropathy in patients with appropriate genetic makeup. Here, we propose a hypothesis whereby painful neuropathy is not a complication of diabetes, but rather occurs as a result of mutations that, in parallel, confer vulnerability to injury in pancreatic beta cells and pain-signaling dorsal root ganglion (DRG) neurons. We suggest that mutations of sodium channel Na(V)1.7, which is present in both cell types, may increase susceptibility for development of diabetes via beta cell injury and produce painful neuropathy via a distinct effect on DRG neurons.
KW - diabetes mellitus
KW - diabetic neuropathy
KW - painful neuropathy
KW - sodium channelopathy
KW - Ne(V)1.7
KW - beta cells
U2 - 10.1016/j.molmed.2014.06.003
DO - 10.1016/j.molmed.2014.06.003
M3 - Article
C2 - 25008557
SN - 1471-4914
VL - 20
SP - 544
EP - 550
JO - Trends in Molecular Medicine
JF - Trends in Molecular Medicine
IS - 10
ER -