Investigating aurora kinase mediated regulation of kinesin nanomotors as a novel therapeutic target for the treatment of chronic pain

Abstract

International Association for the Study of Pain defines pain as An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage . Pain is a protective mechanism of our body that acts as an alarm against various tissue-damaging stimuli, thus it is regarded as the 6th sense which is essential for the survival and wellbeing of organisms. When pain becomes chronic it develops into a devastating medical condition imposing a huge burden on society and healthcare costs. Nociception is the neural process that encodes the noxious stimuli and manipulation in the nociceptive pathways can degrade the usefulness of pain as a protective phenomenon. Despite the progress made in unraveling the pathophysiology behind chronic pain the current therapeutics shows limited efficacy and elicits several side effects, ultimately leading to treatment withdrawal and poor quality of life. Opioids are the most frequently prescribed medication for chronic pain but carry several side effects including sedation, drug addiction, motor incoordination, respiratory depression, hypotension, sleep apnea, constipation, etc. Other treatment options including non-steroidal anti-inflammatory drugs, ion channel blockers, gamma aminobutyric acid analogs have raising contraindications with high reports of adverse effects along with drug-drug interaction. Thus, there is an unmet need for effective pharmacotherapeutics for the treatment of chronic pain without causing severe side effects. Intracellular transport is essential for the cellular homeostasis and survival. Kinesins (KIFs) are the ATP dependent motor proteins that transport variety of receptors from cytosol to the synaptic membrane in an anterograde direction. Kinesin generates mechanical force by utilizing ATP and cause displacement over the microtubule via hand-over-hand movement.