Pro-nociceptive role of the activation of mineralocorticoid receptor in the pathogenesis of painful diabetic neuropathy

Patients with diabetic neuropathy may develop severe pain which persists over several years, resulting from impaired nerve endings in the skin, which originate the pain signals of diabetic neuropathy. Inflammatory processes have been implicated in the genesis and maintenance of chronic pain. The activation of the mineralocorticoid receptor (MR) is believed to promote classical inflammation features such as high levels of oxidative metabolites and proinflammatory cytokines, tissue destruction. Selectively blocking MR’s can prevent the development of pain behaviors induced by neuroinflammation. Since proinflammatory cytokines and mediators were found to have increased in diabetic skin, we propose MR activation may play a pro-nociceptive role in diabetic neuropathy through local inflammation of the skin. Research methods examining MR overexpression in normal skin and selectively blocking MR in the diabetic skin are useful in identifying whether MR activation may bring cutaneous nerve insult and to explain whether MR activation is involved in the progression of painful diabetic neuropathy. If proven, this hypothesis would indicate the MR may potentially act as a novel target for pain therapeutics.