PainRelief.com Interview with:
Rajesh Khanna, PhD
Director, NYU Pain Research Center
Professor, Department of Molecular Pathobiology
Professor, Department of Neuroscience and Physiology
Investigator, Neuroscience Institute
New York University
PainRelief.com: What is the background for this study?
Response: Chronic pain affects an estimated 20-30% of the global population, significantly impacting quality of life and mental health. It poses substantial socioeconomic burdens, with costs relating to healthcare and lost productivity. Despite its prevalence, chronic pain remains underdiagnosed and undertreated worldwide, highlighting a crucial need for enhanced awareness, research, and therapeutic strategies.
Among the many targets being pursued for the development of drugs against chronic pain conditions are key proteins in neurons that are involved in the signaling of pain. A key family of these targets is the voltage-gated sodium channel family. Among them, the Nav1.7 sodium channel plays a critical role in the development and maintenance of chronic pain. It is an integral part of the peripheral nervous system and is highly expressed in nociceptive (pain-sensing) neurons, including the dorsal root ganglia and sympathetic ganglion neurons.
Nav1.7 channels act as a threshold channel, amplifying small sub-threshold depolarizations and generating action potentials, which are the electrical signals responsible for transmitting sensory information, including pain, to the brain. In essence, they work as a key amplifier of signals from peripheral pain-sensing neurons to central pain pathways.
Certain genetic mutations that cause either a gain or loss of Nav1.7 function can lead to conditions associated with altered pain perception. Gain-of-function mutations, which increase the activity of the channel, can lead to pain syndromes like Inherited Erythromelalgia (IE) and Paroxysmal Extreme Pain Disorder (PEPD). In contrast, loss-of-function mutations, which decrease or eliminate the activity of Nav1.7, result in Congenital Insensitivity to Pain (CIP), a condition where individuals are unable to feel pain.
Given this integral role, Nav1.7 has become a focus of interest as a target for new analgesic drugs. The development of Nav1.7 inhibitors could offer a new avenue for more effective and targeted treatment strategies for chronic pain conditions. It’s a promising area of research, though there are still challenges to be met, such as achieving sufficient specificity for the Nav1.7 channel to avoid side effects associated with other sodium channels.
In the NYU Pain Research Center in the College of Dentistry at New York University (https://dental.nyu.edu/research/pain-research-center.html), the Khanna lab is pursuing alternative ways to target Nav1.7 for pain relief.