Funded Projects

This project supports a post-baccalaureate trainee develop skills needed to pursue a career in clinical pain research. The research will use molecular tools to study nerve, joint, muscle, and fascia tissues from individuals with chronic low back pain who had spine surgery. The research will include working with patients, designing clinical studies, and sharing results. 

Opioids affect the body by attaching to certain types of receptors that attach to G-proteins (particularly, a subtype called G-alpha). Opioids vary in their ability to provide pain relief as well as in their ability to require more drug to provide a response, known as tolerance. This project will explore the potential of various G-alpha subunits to increase or decrease opioid receptor signaling. The research findings will lay the groundwork for tailoring G-alpha related opioid effects to provide more pain relief while being less addictive.

Routine treatment of pain with prescription opioid medications may evolve into opioid use disorder, addiction, and potentially overdose. New, non-opioid molecular targets for pain are needed as a key element of responding to the opioid and overdose crisis. Ion channels are molecular gateways that convert electrical signals into physiological responses, and many have been implicated in transmitting pain signals. The ion channel Kir6.1/KCNJ8 has been linked to the control of postoperative and cancer pain. Studies in animal models show that low levels of this ion channel are evident after an injury. This research will identify compounds that can open the Kir6.1/KCNJ8 channel as potential treatment strategy for pain.

This project will use a variety of state-of-the-art technologies to generate a comprehensive  gene expression map of human peripheral nerves. The research will enhance understanding about genes involved in various painful conditions associated with nerve damage (neuropathies) resulting from injury or disease. This research will analyze DNA sequences of individual neuronal and non-neuronal cells in human nerve cells (from individuals with and without pain located outside the spinal cord that are involved in pain signal transmission. The findings, together with other imaging and computational approaches, will be used to generate a spatial atlas of the human dorsal root ganglia – a key hub for pain communication between the brain and spinal cord.

Complex regional pain syndrome is a difficult-to-treat chronic condition that causes excess and prolonged pain and inflammation after injury to an arm or leg and includes damage to skin of affected limbs. Although it is known that aberrant immune system function plays a role in this condition, the details remain unclear about how this occurs – in particular, through the adaptive immune system that relies on specialized immune cells and antibodies to protect the body from harm.  This project will study the role of certain immune cells (T cells) that circulate throughout the body or reside in bone using both rat or human bone samples from patients with complex regional pain syndrome.

Endometriosis is an often-painful disorder in which uterine tissue grows outside the uterus. Treatment of endometriosis-associated pain involves use of opioids in many women. This project aims to study a culprit gene thought to be involved with the disorder (capillary morphogenesis gene or CMG2) as a target for new, nonopioid pain medications. The research will also clarify how CMG2 s affects endometriosis-associated pain to test the effects of new medications for endometriosis pain.

This project will identify molecular characteristics of human sensory neurons and non-neuronal cells from the human dorsal root ganglia. This structure located outside the spinal cord is integrally involved in communicating pain signals to and from the brain. The research will use molecular approaches to characterize tissues obtained from organ donors and in patients who experience chronic pain. The findings will also help generate a connectivity map, or “connectome,” of nerve cell connections between the dorsal root ganglia of the spinal cord and the brain.

Oral cancers are painful and often require use of opioid medications to manage pain. However, the effectiveness of opioids often wanes quickly, and many patients require higher doses because they develop tolerance to these medications. This project will study the potential value of blocking epidermal growth-factor receptors interacting with peripheral nerves to treat oral cancer pain. The findings will advance understanding of the molecular mechanisms underlying oral cancer pain and provide a rationale for repurposing epidermal growth-factor receptor blockers, which is already approved for head and neck cancer treatment for treating oral cancer and associated pain.

Chronic visceral pain disorders, such as interstitial cystitis/bladder pain syndrome, are among the most difficult types of pain to treat. This project will conduct a detailed analysis of an enzyme thought to be involved with the disorder (purine nucleoside phosphorylase, or PNPase) as a target for new nonopioid pain medications to treat interstitial cystitis/bladder pain syndrome. The research will lay the groundwork for developing targeted treatments for visceral pain disorders.

This project will use state-of-the-art technologies to analyze individual cells to characterize how human pain receptors communicate pain between the human dorsal root ganglia and the brain – including how the signals vary across diverse populations. This research will generate useful, high-quality human data about pain for further analysis and re-use by other scientific teams, toward identifying and prioritizing novel therapeutic targets for pain.

Interstitial cystitis/bladder pain syndrome is a debilitating disease affecting many women. Opioid-based pain management is a common feature of current treatment approaches but is associated with the risk of addiction. The causes of this disorder remain unknown, and no effective treatments are available. This project will provide new insights using genetic, medication-based and other approaches in a mouse model, along with single-cell gene expression studies conducted with cells from mice and human patients who have this condition. The analyses will help provide targeted, safe, and effective treatment approaches for individuals with interstitial cystitis/bladder pain syndrome.

Chronic pain is a debilitating condition for which there is a pressing need for safe, effective treatments. Neurostimulation therapies that target nerve structures such as the dorsal root ganglion (DRG) and the spinal cord, have shown promising results for treating chronic pain, but researchers don’t know how they work. This project focuses on two prevailing models used to explain the therapeutic effects of neurostimulation: the gate-control model in which pain signals are blocked from reaching the brain and the T-junction filtering model in which pain signals are blocked from reaching the spinal cord. Strategies will include innovative behavioral, electrophysiological, imaging, and computational modeling techniques. The results of these studies will help explain why neurostimulation therapies work and potentially offer new treatment strategies for improved pain relief.

Spinal cord stimulators (SCS) and related devices are commonly used for hard-to-treat pain conditions, but how they work remains unclear. This knowledge is important for improving device design and stimulation patterns, as well as for determining which patients will benefit. Through a series of clinical studies in patients with SCS devices, this project will explore the hypothesis that SCS devices reduce pain by changing the excitability of peripheral sensory nerve fibers in the spinal cord. The results should guide development of biomarkers to advance research further.