Category: Research

Histamine, acting through all four types of histamine H1-H4 receptors, is arguably the most pleiotropic molecule in the human body. Since the cloning of H3R in 1999, there has been an increased interest within the pharmaceutical industry to discover and develop ligands to this receptor to target several diseases including neuropathic pain. However, while evidence supporting H3Rs expression in nociceptive pathways, including our earlier studies showing H3R on a population of A delta fibres that regulate pain sensitivity, and a role for H3R in the modulation of mechanical pathological pain is continuously increasing, many of the findings reporting the functional implication of H3R in chronic pain have been somewhat contradictory. This discrepancy led us to a hypothesis that this is due to both the central and peripheral nervous system access of the drugs tested thus far. Recent development of a selective and peripherally acting/centrally-sparing H3R ligands has provided an interesting tool for validation of peripheral H3R as a potential target for therapeutic intervention in chronic pain, particularly in peripheral neuropathies where pharmacological effectiveness would be desired, but not limited to, peripheral nervous system and pain-related peripheral sensitization.

Spinal cord stimulation (SCS) is used as a safe and effective option for multiple chronic neuropathic pain disorders. While different stimulation paradigms have been implemented into clinical practice, it remains unclear how these paradigms affect the spinal and supraspinal circuits. Evoked compound action potentials (ECAP) have been successfully used as an objective measure to quantify the effect of SCS in terms of neural activation of dorsal column fibres, as they represent the summation of action potentials generated from the activated fibres. ECAP recordings allow us to optimize SCS treatment by applying stimulation parameters in a consistent and controlled manner, and to investigate their effects on neural responses and SCS-induced pain relief.

Dental pain mechanisms remain poorly understood. Outcomes from current approaches to managing acute dental pain are suboptimal. EXTIRPATE focusses on developing a biological model to better understand peripheral and central pain mechanisms, explore the effect of current approaches on these mechanisms and investigate new treatment approaches.

This study aims to identify the differential gene and protein expression associated with pain pathways in iPSCs-derived sensory neurons obtained from Parkinson’s patients or patients with TSC mutations vs iPSCs controls sensory neurons using genetic and proteins analyses. Then determining the functional abnormalities in patients’ iPSC-derived sensory in response to pain stimuli by using functional analyses e.g., calcium imaging, patch-clamp or multi-electrode arrays. By identifying the potentially deregulated proteins in patient models, it will be possible to pinpoint therapeutic targets to reverse the abnormal functional behaviours of patients’ sensory neurons through pharmacological intervention, or by genetic manipulation of the target genes using CRISPR-Cas9 technology.

The experience of jaw pain that lasts for more than a few months can be an uncertain experience both for patients and professionals. Management may fall between the roles of dentist or GP and many people are unclear about who to consult. Self-management is recommended as first-line treatment, possibly alongside other conservative options. In practice treatments and explanations that are offered can be varied and inconsistent. This study aims to explore the experiences of people who have sought help for persistent jaw pain of treatment and explanations offered and of being introduced to and using self-management. Initial results indicate that experiences can be varied and those who use self-management typically learn about it from sources other than their dental or medical appointments.

Pain is a salient percept that can draw our attention away from our current task so we can deal with potential bodily harm. We are interested in how our thoughts and actions can help us deal with pain, for example by distracting us from a painful stimulus. To address this, we use different tasks to measure how cognition and emotion reduce the pain intensity people feel in response to a painful stimulus. We also investigate brain mechanisms underlying pain perception, particularly in individuals who suffer from persistent chronic pain, and use different stimulation methods that may help modulate pain intensity.

The kynurenine pathway is responsible for the catabolism of the essential amino acid kynurenine. This pathway has been linked to acute and chronic pain in animal models of viral infections. Research by the team has shown upregulation of this pathway in pulpititis (toothache) and it appears to be pushing the pathway towards neuroinflammation and pain. This project therefore looks to examine the kynurneine pathway as a means to therapeutic reduce the pain experienced during toothache and potentially persistent pain which can follow. 2. There is an absence of topically applied medications for use in managing dental pain. Much of this is due to the complexities in examining potential therapeutics with animal models often used. This project looks to develop a lab made (in vitro) cell model of dental pulp using stem cells. This will reduce our reliance on animal models in keeping with the NC3Rs, but also speed up drug screening as compounds can be assessed more easily and at a greater range of doses prior to further investigation ensuring only the most promising are taken forward.