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Papers of the Week

Papers: 1 Aug 2020 - 7 Aug 2020

Animal Studies

2020 Jul 30

Neurosci Lett

Changes in expression of Kv7.5 and Kv7.2 channels in Dorsal Root Ganglion Neurons in the Streptozotocin Rat Model of Painful Diabetic Neuropathy.


Diabetic peripheral neuropathic pain (DPNP), the most debilitating complication of diabetes mellitus, is resistant to current therapy. The pathogenesis of DPNP is still elusive, but several mechanisms have been proposed including abnormal hyperexcitability of dorsal root ganglion (DRG) neurons. The underlying molecular mechanisms of such aberrant hyperexcitability are incompletely understood. Using the streptozotocin (STZ) rat model of DPNP, we have recently provided evidence implicating neuronal K7 channels that normally exert a powerful stabilizing influence on neuronal excitability, in the abnormal hyperexcitability of DRG neurons and in pain hypersensitivity associated with DPNP. In the present immunohistochemical study, we sought to determine whether K7.2 and/or K7.5 channel expression is altered in DRG neurons in STZ rats. We found 35 days post-STZ: (1) a significant decrease in K7.5-immunoreactivity in small (<30 µm) DRG neurons (both IB4 positive and IB4 negative) and medium-sized (30-40 µm) neurons, and (2) a significant increase in K7.2-immunoreactivity in small (<30 µm) neurons, and a non-significant increase in medium/large neurons. The decrease in K7.5 channel expression in small and medium-sized DRG neurons in STZ rats is likely to contribute to the mechanisms of hyperexcitability of these neurons and thereby to the resulting pain hypersensitivity associated with DPNP. The upregulation of K7.2 subunit in small DRG neurons may be an activity dependent compensatory mechanism to limit STZ-induced hyperexcitability of DRG neurons and the associated pain hypersensitivity. The findings support the notion that K7 channels may represent a novel target for DPNP treatment.