The role of protein kinases in diabetic neuropathic pain: an update review.

Abstract

Objectives: Diabetic neuropathic pain (DNP) is a debilitating symptom of diabetic neuropathy which seriously impairs patient's quality of life. Currently, there is no specific therapy for DNP except for duloxetine and gabapentin that show limited utility in alleviating DNP. The present review aims to discuss the central role of protein kinases in the pathogenesis of DNP and their therapeutic modulation.

Methods: Scopus, PubMed, and Google scholar were searched up to January 2022 to find relevant studies with English language in which the roles of proteins kinases in DNP were examined.

Results: DNP is associated with hyperactivity in pain sensory neurons and therapies aim to specifically suppress redundant discharges in these neurons without affecting the activity of other sensory and motor neurons. Transient receptor potential vanilloid 1 (TRPV1) and purinergic 2 × 7 receptors (P2 × 7R) are two receptor channels, highly expressed in pain sensory neurons and their blockade produces remarkable analgesic effects in DNP. The activities of receptor channels are mainly regulated by the protein kinases whose modulation provides remarkable analgesic effects in DNP models.

Conclusion: Capsaicin, TRPV1 modulator, is the only agent successfully examined in clinical trials with promising effects in patients with DNP. Current data suggest that blocking calcium calmodulin dependent protein kinase II (CaMKII) is superior to other approaches, considering its pivotal role in regulating the pain neuron potentials. By this means, DNP alleviation is achievable without affecting the activity of other sensory or motor neurons.