Murine model and mechanisms of treatment-induced painful diabetic neuropathy.
Authors Nicodemus JM, Enriquez C, Marquez A, Anaya CJ, Jolivalt CG
Submitted By Corinne Jolivalt on 2/19/2018
Status Published
Journal Neuroscience
Year 2017
Date Published 6/1/2017
Volume : Pages 354 : 136 - 145
PubMed Reference 28476321
Abstract Diabetes mellitus represents a group of metabolic diseases that are
characterized by hyperglycemia caused by either lack of insulin production or a
reduced ability to respond to insulin. It is estimated that there were 347
million people worldwide who suffered from diabetes in 2008 and incidence is
predicted to double by 2050. Neuropathy is the most common complication of
long-term diabetes and approximately 30% of these subjects develop chronic
neuropathic pain. A distinct acute, severe form of neuropathic pain, called
insulin neuritis or treatment-induced painful neuropathy of diabetes (TIND), may
also occur shortly after initiation of intensive glycemic control, with an
incidence rate of up to 10.9%. The pathological mechanisms leading to TIND,
which is mostly unresponsive to analgesics, are not yet understood, impeding the
development of therapies. Studies to date have been clinical and with limited
cohorts of patients. In the current study, we developed chronic and acute
insulin-induced neuropathic pain in mice with type 2 insulin-resistant diabetes.
Furthermore, we determined that insulin-induced acute allodynia is independent
of glycemia levels, can also be induced with Insulin-like Growth Factor 1 (IGF1)
and be prevented by inhibition of AKT, providing evidence of an insulin/IGF1
signaling pathway-based mechanism for TIND. This mouse model is useful for the
elucidation of mechanisms contributing to TIND and for the testing of new
therapeutic approaches to treat TIND.