Blockage of HCN Channels with ZD7288 Attenuates Mechanical Hypersensitivity in Rats Model of Diabetic Neuropathy

Abstract

Background: Diabetes is a chronic condition that affects millions of people worldwide. The disease can have severeimpact on many systems of the human body particularly the nervous system. Indeed, chronic peripheral nerve pain, also known as peripheral neuropathic pain (NP), is the most common complication caused by diabetes. There have existed preclinical researches that were performed using different types of Rodents as models of Chronic Pain. Such studies have proven that hypersensitivity to pain is caused, at least partially, by increased excitability of primary afferent dorsal root ganglion (DRG) neurons that send the sensory information from the periphery to the brain. However, the mechanism of this hyperexcitability is yet to be known. Aims: The primary aim of the continuing work is to examine the hypothesis that Hyperpolarization-activated Cyclic Nucleotide gated (HCN) channels (that are known to regulate excitability of the neurons) are involved in the pathophysiology of diabetic neuropathic pain (DNP). Methods and Results: To examine this hypothesis, we used a rat model of diabetic neuropathy by 60 mg/kg, i.p., of (streptozotocin (STZ), a toxin of pancreatic β-cells that release insulin) and tested the effects of blocking the HCN channels with a selective blocker, ZD7288, on two pain behaviours (mechanical hypersensitivity/allodynia, and heat hypersensitivity/hyperalgesia) in these STZ treated rats. The results showed that intraplantar administration of ZD7288 (100 μM) reduced mechanical allodynia but not heat hyperalgesia. Conclusions: The results are in agreement with previous investigations which used other models of chronic pain and suggest that HCN channels may be a good target for developing new analgesics (pain killers) for chronic pain.