Solutions and capabilities
Pain research presents a unique set of challenges due to its multifaceted nature. Pain can result from a wide range of underlying physiological causes, including injury, disease, or dysfunction in various systems (e.g., musculoskeletal, neurological, or visceral). Additionally, pain lacks objective outcome measures and involves complex processing by both the peripheral and central nervous system.
To address these challenges, CHDR developed PainCart®, a validated test battery encompassing a diverse range of evoked pain models, including thermal, electrical, chemical, and mechanical pain. PainCart® is able to assess the effects of potential analgesic drugs in healthy subjects and patient populations. The test battery can easily be incorporated in phase 1 trials, facilitating the evaluation of safety and tolerability combined with analgesic effects during the early phases of drug development. Furthermore, combining PainCart® with NeuroCart® will also lead to valuable insights into a compound’s overall central nervous system (CNS) effects, contributing to a more comprehensive understanding of its therapeutic potential.
Innovative pain research
To enhance the applicability of PainCart®, CHDR is exploring innovative approaches to systematically modulate both central and peripheral pain mechanisms. These research initiatives, primarily self-financed, aim to advance the development of novel biomarkers for pain research. One recent project focused on utilizing virtual reality (VR) to address the affective component of pain. In this study, VR was employed to influence pain responses to real-time electrical or pressure-based stimuli by introducing varying emotional contexts.
Ventilation studies
Respiratory depression is a potential side effect of many analgesics and other centrally acting drugs. Especially opioids are well known for their respiratory depressant effect. In collaboration with the anesthesiology and pain medicine department of the Leiden University Medical Center, CHDR performs studies evaluating the influence of analgesic drugs (and other centrally acting compounds) on ventilation. Read more here.
Patient studies
Translational studies involving healthy participants are crucial in bridging the gap between preclinical animal research and clinical trials. However, clinical studies with patient populations remain an indispensable step in the novel drug development process, as no pain model can fully mimic the complexity of clinical pain. At CHDR, we possess extensive expertise in the conduction of clinical trials in patients with chronic pain conditions such as radicular pain, painful diabetic neuropathy and fibromyalgia. Depending on the target patient population and the sponsor’s specific requirements, studies can be conducted either at our clinical research unit or within a hospital setting. Through our close collaboration with the Department of Anesthesiology and Pain Medicine at Leiden University Medical Center, we ensure the efficient execution of these studies.
Exploring a Novel S1P Receptor Modulator for Pain Relief and CNS Target Engagement
Recently, we have conducted an innovative phase 1 study, investigating a novel S1P receptor modulator designed to address central nervous system (CNS) disorders. In a target engagement proof-of-concept (POC) study, we used PainCart® to assess the compound’s effects on both central and peripheral pain responses, including its impact on our capsaicin-induced pain model. The study revealed a dose-dependent reduction in allodynia, supporting the compound’s potential as a non-opioid treatment for chronic pain. Additionally, we conducted a transcranial magnetic stimulation (TMS) POC study to evaluate the effects of the compound on cortical excitability, utilising EEG and EMG to gain valuable insights into its mechanism of action. Through these studies, we successfully demonstrated the compound’s ability to engage CNS targets and reduce neural hyperexcitability, representing a significant advancement in the development of novel pain therapies.
Practical answers to important research questions
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Using PainCart®, we are able to assess the analgesic potential of new compounds in both healthy participants and chronic pain patients. The tool allows for a direct comparison of the novel compound’s PainCart® profile with those of registered analgesics. Additionally, PainCart® provides valuable insights into the underlying mechanisms of analgesic effects and offers a detailed understanding of the subjective drug effects experienced by human participants.
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By comparing the compound’s PainCart® profile with that of well-established analgesics, we can provide valuable guidance for future patient studies. For instance, if the compound’s profile resembles that of ibuprofen, its target population is likely to differ from those who respond primarily to other analgesics such as pregabalin or morphine. Our pain models can help researchers identify the patient populations most likely to benefit from their new compound.
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Several mechanisms are involved in the processing of pain. By utilizing the nociceptive tasks integrated into PainCart®, such as the capsaicin pain test and the conditioned pain modulation response, we can gain valuable insights into whether a compound is more effective at targeting peripheral pain, central pain, or both.
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CHDR has extensive experience in studying the effects of drugs on the central nervous system (CNS) using NeuroCart®, our comprehensive neurophysiological and cognitive test battery. By combining NeuroCart® and PainCart® in the same study, we can gain a deeper understanding of a compound’s analgesic potential while also identifying any potential effects on the CNS. This approach allows us to besides pain also identify and quantify the drug’s impact on alertness, body stability, and subjective drug-related effects, such as feelings of euphoria.
