Kinesins: Motor Proteins as Novel Target for the Treatment of Chronic Pain
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Kinesins: Motor Proteins as Novel Target for the Treatment of Chronic Pain P. A. Shantanu 1 & Dilip Sharma 1 & Monika Sharma 1 & Shivani Vaidya 1 & Kuhu Sharma 1 & Kiran Kalia 1 & Yuan-Xiang Tao 2,3 & Amit Shard 4 & Vinod Tiwari 1 Received: 16 April 2018 / Accepted: 21 August 2018 # Springer Science+Business Media, LLC, part of Springer Nature 2018
Abstract Kinesins are one of the neoteric and efficacious targets recently reported to play an important role in the initiation and progression of chronic pain. Kinesins are anterograde microtubule-based motor proteins that are involved in trafficking of receptors including nociceptors and progression of pain. The specific kinesin and regulatory proteins interplay is crucial for the delivery of nociceptors to the synapse. If this complex and less understood interplay is inhibited, it may result in a decrease in central sensitization, and thus attenuation of pain. This review is focused on the transportation process of receptors/cargos, the role of regulatory proteins influencing the respective kinesin, and their relationship with chronic pain. The review also features specific strategies adopted by researchers for targeting kinesin and chronic pain. Considering the recent preclinical success of kinesin inhibition in pain, it is expected that inhibitors for kinesin or enzymes responsible for kinesin activation could be developed or repurposed as alternative, safe, and potential therapies for the treatment of chronic pain. Keywords Bone cancer pain . Calcium calmodulin kinase 2 . Cyclin-dependent kinesins . KIF13B . KIF17 . NMDA, pain . Sodium channels . TRPV1
Introduction Chronic Pain: a Perpetual Problem with Limited Therapies Even after more than a century of studying pain and its underlying mechanisms, we are unable to develop the effective therapies against it. Recent studies indicate that around 20– 25% of world’s population suffer from some kind of chronic pain out of which 35% do not respond to currently available
* Vinod Tiwari [email protected] 1
Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar, Gujarat, India
2
Neurosicience Research Institute, Zhengzhou University Academy of Medical Sciences, Zhengzhou, Henan, China
3
Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ, USA
4
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar, Gujarat 382355, India
drugs in clinics [1]. Chronic pain is a highly prevalent disease with astounding health care cost globally. It has become the leading cause of disability in the USA and the seventh leading one worldwide [2]. Moreover, the therapies which are available either leads to inadequate pain relief or causes severe side effects including but not limuted to drug addiction, hallucinations, respiratory depression, constipation, and even death in some cases [3]. Pain, as International Associati
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