Funded Projects

Analgesia for post-operative populations remains a significant health need that calls for innovative therapies which improve both safety and outcome measures. Recent FDA drug safety warnings and studies focusing on post-operative analgesia have highlighted the imperative need for new approaches that can be utilized for common clinical scenarios. Accordingly, novel treatment options that are safe and afford additional benefit in relief of pain are needed. In this proposal, the development of an innovative surgical sealant technology is proposed that functions at the level of the surgical wound bed and actively delivers local pharmacologic agents to therapeutically address post-operative pain. New formulations of several analgesic regimens will be assessed for their ability to seal wounds and provide appropriate pain management.

Temporomandibular joint (TMJ) disorders, which affect the joint connecting the lower jaw and the skull, are common and difficult chronic pain conditions. Pain management strategies that harness the body’s own pain relief mechanisms (including placebo effects in which pain relief cannot be attributed to a specific treatment), can reduce the severity and duration of TMJ-related chronic pain. Although research suggests that placebo effects may have a genetic basis, few, if any, genetic studies have examined this possibility in individuals with TMJ disorders. This project will use in-depth genetic, sociodemographic, clinical, and psychological data collected from adults with chronic TMJ disorders to better understand how the placebo effect works.

Sickle cell disease is an inherited blood disorder affecting about 100,000 Americans and more than 20 million people worldwide. It is caused by a mutation in the gene for beta-globin that results in the characteristic sickled shape of red blood cells, life-long severe pain, and shortened lifespan. Sickle cell disease pain episodes are usually unanticipated, making it hard for people with the condition to manage their pain and putting them at risk for increased use of opioids and poor health outcomes. This project will use existing real-time health data to identify factors that can predict onset, severity, and worsening of daily pain in children with sickle cell disease.

There is an urgent need for non-opioid post-operative pain management solutions.  This research is developing a naturally absorbable polymer film that can release controlled amounts of the non-opioid analgesic bupivacaine – aiming to manage pain for several days following surgery. Project objectives are to optimize the timing of drug release, develop manufacturing standards, determine effective dosage for preserving motor function, and determine safety and efficacy in mouse models of neuropathic pain. Continued development of this film delivery system may lead to a new, non-opioid therapeutic strategy that could be combined with local anesthesia for up to 4 days after surgery to reduce or potentially eliminate opioids use.

Osteoarthritis is one of the most common joint diseases affecting Americans. Osteoarthritis is particularly high among veterans with a service-related disability. This project will develop and refine a wireless ultrasound device that increases the penetration of over-the-counter pain medications into the body, which is expected to reduce pain. The research will conduct safety and clinical testing toward commercializing this technology. 

There are significant and persistent gaps in knowledge about effective pain management for acute and chronic sickle cell pain. This is an area of relevant interest for the NIH HEAL Initiative's Early Phase Pain Investigation Clinical Network (EPPIC-Net). In order to provide guidance for hospital-based administration of the medication ketamine, this project will conduct a cross-sectional survey study of healthcare professionals within EPPIC-Net who provide care for people with sickle cell disease. This information can be used to design a clinical protocol for a multisite, randomized clinical trial of sub-anesthetic (low) doses of ketamine for challenging vaso-occlusive episodes (“pain crises”) in people with sickle cell disease.

Neuropathic pain adversely affects quality of life and remains challenging to treat, presenting high unmet medical need. One example of this type of pain, chemotherapy-induced peripheral neuropathy, is a chronic, severely debilitating consequence of cancer therapy for which there are no effective treatment strategies. This research is testing a new cannabidiol (CBD) analogue (KLS-13019) with neuroprotective properties and which has improved drug-like properties compared to CBD. This project will optimize the process to manufacture KLS-13019, develop analytical methods, optimize its formulation, evaluate its safety and toxicity, and test KLS-13019’s efficacy of in a rat model of chemotherapy-induced peripheral neuropathy.

There are currently few effective therapies available for chronic nerve injury-induced pain, associated anxiety, and depression. This project aims to extend previous research aiming to uncover the mechanism of action of artificially modified immune molecules (humanized cholecystokinin-2 receptor [CCKBR] single-chain variable fragments [scFv]) on human neurons and how it reverses chronic pain and anxiety-like behaviors in mouse models. This potential treatment approach offers important advantages over existing therapies, including extreme specificity, higher affinity, brain/nerve penetrance, safety, and reduced self-immunogenicity.

Many molecular gates known as ion channels control the flow of electrical signals to sensory neurons and are thus key mechanisms and targets for understanding and interrupting pain signals. Recent breakthroughs in structural and computational biology shave illuminated specific molecular shapes of ion channels, which permits the improved design and refinement of small, stable protein-like molecules (peptide antigens). These peptides can stimulate an immune response that can then be targeted with a bioengineered antibody to match the peptide antigen. This project will test bioengineered antibodies in a rat model of chemotherapy-induced peripheral neuropathy within a region of the rat spinal cord that transmits signals to and from the brain.

Chronic pain is a major healthcare burden. However, the types and underlying mechanisms of pain vary greatly, as do patient responses to currently available pain medications. Inflammation in the nervous system (neuroinflammation) is involved in several types of pain, and targeting key molecules involved in neuroinflammation is therefore a promising treatment approach. The chemokine receptor system, a complex network of more than 20 different receptors and more than 80 molecules that bind to these receptors, has a central role in neuroinflammation. Researchers do not yet fully understand the functioning of this network and how specific receptors vary in different chronic pain conditions. Therefore, this project aims to further characterize the expression of one specific receptor, using samples collected from participants in clinical trials evaluating a compound that interferes with the receptor’s function. This information should allow researchers to classify pain patients and identify those most likely to benefit from a treatment with compounds targeting the receptor.

The proposed Fast Track SBIR effort will develop and validate the reliable, low-cost KnowPain instrument. KnowPain will objectively and quantitatively assess the functional impact of chronic pain using measures derived from six degrees-of-freedom motion, heart rate, skin surface temperature, and skin conductivity collected via a specially designed, ergonomic wrist-worn biometric sensing instrument. The new assessment instrument will apply advanced psychometric methods to both physiologic and kinematic data to provide precise scores for functional impairment due to chronic pain. The assessment results will be presented to the clinician in an easy-to-understand report and will include longitudinal results, confidence estimates, and normative data to enable comparisons both within and between patients. The system will include provision to interface with electronic medical records. Accurate functional assessment is a crucial component in the effective treatment of chronic pain. The proposed approach will supplement existing methods for assessing patient function by providing novel and highly complementary information for a more complete (and often unobserved) picture of the impact of chronic pain on patient function. KnowPain measures will provide important data on the practical consequences of pain and on treatment efficacy.