Therapeutic potential of PKC inhibitors in painful diabetic neuropathy
- 1 September 2001
- journal article
- review article
- Published by Taylor & Francis in Expert Opinion on Investigational Drugs
- Vol. 10 (9) , 1653-1664
- https://doi.org/10.1517/13543784.10.9.1653
Abstract
Diabetic neuropathy accompanied by anomalies in pain perception is one of the most frequent complications in insulin-dependent diabetes in humans. Many clinical and experimental studies have suggested that diabetes or hyperglycaemia alters pain sensitivity. In humans, diabetic neuropathy can be associated with burning, tactile hypersensitivity. Behavioural reactions of hyperalgesia in animal models of diabetes have been described. However, the aetiology of these disturbances is still unknown, although metabolic factors such as hyperglycaemia or neurotransmitter alteration may be involved. Activation of protein kinase C (PKC) has been implicated in changes in pain perception. Phorbol esters, which activate PKC, enhance the thermal hyperalgesia in diabetic mice and enhance nociceptive responses after tissue injury induced by formalin. Electrophysiological experiments have shown that activation of PKC leads to long-lasting enhancement of excitatory amino acid-mediated currents in dorsal horn neurons and trig...Keywords
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