Projects – Research Focus
The Role of TLR4 in Chronic Pain
The Chakravarthy Laboratory is currently working with Eisai Pharmaceuticals in developing a new method to deal with post-operative pain. Chronic persistent post-operative pain (CPOP) is a devastating outcome from any type of surgical procedure. Depending on the type of surgery, the incidence of CPOP can range from between 5-85%, and to date there are no standard treatments. Our laboratory is interested in advancing new preventative analgesia for post-operative pain that targets the TLR4 receptor family. Currently, we are in the process of pursuing phase 2 clinical trials to advance this novel treatment for various pain indications.
Studying Mechanisms behind Chronic Pain Following Traumatic Brain Injury (TBI)
Our laboratory has been specifically investigating the role that caveolins play in mitigating chronic pain following traumatic brain injury (TBI). Chronic pain in Veterans with TBI presents a daunting scenario for both these individuals and their medical providers. Military personnel operate in a unique environment that places them at particular risk of sudden ballistic forces capable of producing neuro-polytrauma. Half of all combat injuries are blast-related, resulting in various forms of tissue damage, with half of those victims suffering from TBI. We are examining the role that caveolins play in mitigating the transition to chronic pain following TBI.
Few diseases are as responsible for the significant annual tolls of morbidity, mortality, and economic loss, than influenza virus infections. They appear predictably each year as seasonal influenza outbreaks, which result in over 30,000 deaths and 100,000 hospitalizations during a typical season in the United States. They also appear unpredictably as pandemics and wreak havoc and death on a global scale. The influenza virus continually undergoes genetic variations through antigenic drift, and more drastically through antigenic shift. This rapid variability necessitates the requirement for the rapid development of vaccines in conjunction with ascertaining the pathogenesis, host-to-host transmission, and susceptibility to anti-viral drugs. Thus, there is an urgent need to develop powerful model systems to quickly evaluate influenza viruses, as well as develop new vaccine alternatives. The Chakravarthy Lab, in collaboration with the United States Centers for Disease Control and Prevention is currently developing new transgenic animal reporter systems for screening new vaccine candidates. We are also advancing the use of new biomimetic nanotechnology platforms for gene therapy treatments for seasonal and pandemic flu.
Non-Invasive Wearable Electrochemical Sensor for the Detection of Opiates and THC
The prescribing of opioid medications for chronic pain patients poses significant risks and challenges. These risks include, but are not limited to, unintentional opioid overdose, diversion of prescription medication to family members or others, and/or potential drug interactions with other medications or abused substances. In 2010, approximately 5.1 million people used prescription pain medications for non-medical purposes. Based on data from the National Institute on Drug Abuse, it is estimated that 1 in 20 twelfth grade high school students abused controlled-release oxycodone, and 1 in 12 abused hydrocodone in the last 12 months. Greater than 54% of those who abused prescription pain relievers for non-medical reasons received their medications from family or friends, which suggests that a significant amount of drug diversion occurs. The Chakravarthy Laboratory in collaboration with the UC San Diego School of Engineering, and UC Center for Wearable Sensors is working on a low cost sensor platform for the detection of opiates and THC.
Development of Novel Transdermal Drug Delivery Systems Targeting Neuropathic Pain
Over 50 million people in the US suffer from persistent pain, with 3 million experiencing neuropathic pain. Chronic pain is one of the most common and costly disorders, and is a burden comes with many diseases including, but not limited to, arthritis, cancer, and depression. Beyond the lack of suitable treatment modalities, the effective delivery of these treatments is also lacking. The Chakravarthy Laboratory is working with the UCSD Department of NanoEngineering to advance a new ultrasound guided transdermal drug delivery platform for pain medications.
Physicians in the United States have been using spinal cord stimulation (SCS) to treat chronic pain conditions since it was first developed nearly half a century ago. Inspired by the seminal gate-control theory of pain proposed by Melzack and Wall, the conventional paradigm of SCS utilizes tonic 40-60 Hz stimulation that activates dorsal columns to elicit paresthesia over a patient’s painful region. This paresthesia-based SCS has proven to be an effective treatment modality for 40-50% of patients with refractory pain conditions, including complex regional pain syndrome and failed back surgery syndrome (FBSS). However, conventional SCS has several limitations, such as limited clinical indications, suboptimal or inadequate pain inhibition (e.g., non-responders), and progressive reduction of treatment effects over time. The Chakravarthy Laboratory in collaboration with the UCSD Integrated Electronic and Bio Interfaces Laboratory is developing new paradigm shifting neuromodulation technologies and spinal cord stimulation devices.