Pain is one of CHDR's main focus areas. Over the years, CHDR has developed PainCart®, a validated battery of tests consisting of a wide range of evoked pain models. PainCart can for example be used to study the analgesic properties of new compounds early in the drug development process. The overall goal of the pain group at CHDR is to optimise the translational step from early preclinical studies to clinical studies involving specific patient groups.

Highlights

  • CHDR has experience studying pain in healthy subjects and in patients with chronic pain (e.g. sciatica, painful diabetic neuropathy or painful idiopathic axonal neuropathy).
  • PainCart includes a wide range of models in which various forms of pain can be induced in healthy subjects, thereby mimicking the mechanisms of action underlying various forms of pain.
  • PainCart has been validated using a variety of well-known analgesics, providing a library of profiles for various classes of analgesic drugs against which new compounds can be compared.
  • At CHDR we keep improving and expanding our toolbox of pain models and tests. We for example now use virtual reality, cytokine activation, and sleep deprivation to reduce the pain threshold in ways that are reminiscent of peripheral and central sensitization.
  • We can also use EEG to measure evoked potentials, providing an objective measure of pain with extremely high temporal resolution.
  • Combining PainCart with NeuroCart can yield a wealth of important information regarding a compound’s CNS effects.

A closer look at pain research

Pain research can be quite challenging. Pain can be caused by a wide variety of diseases and conditions, and nearly every patient can experience pain. Furthermore, pain is highly subjective. This is challenging enough with human subjects, but it is considerably more challenging in studies involving animals, which limits the usefulness of animal models in pain research. This makes evoked pain models in human subjects so important in translational research, particularly in early-stage clinical drug development.

PainCart®

PainCart®, is CHDR's validated battery of tests consisting of a wide range of evoked pain models, including thermal, electrical, chemical, and mechanical pain. PainCart helps us profile the effects of candidate analgesic drugs in healthy subjects. Using PainCart, we can establish both safety and tolerability in the early phases of development, and we can determine the compound’s pharmacokinetics profile. A clear advantage of PainCart is its fully mobile format, allowing researchers to perform the complete battery of tests while on the go. Moreover, the built-in software ensures consistent testing and reliable data capture, handling, and storage.

PainCart 

Studies involving patients

Translational studies involving healthy subjects can go a long way toward bridging preclinical animal experiments and trials in patients. However, clinical studies involving patients will always be an essential step in the development process, as no pain model can replicate all aspects of clinical pain. At CHDR, we have extensive experience in clinical drug development, including studies involving patients with a wide range of somatic and/or psychiatric disorders. Depending on the target patient population and the sponsor’s needs, studies can be conducted in our clinical research unit or in a hospital setting.

Innovative pain research

To increase the applicability of PainCart, CHDR is currently investigating new ways to systematically interfere with central and/or peripheral mechanisms of pain. These research projects ‒ which are primarily self-financed by CHDR ‒ will likely make it possible to study a much wider range of drug effects. An example of such a project is interference with the affective component of pain with the use of virtual reality (VR). We plan to use VR to induce a stronger pain response to electrical or pressure-based stimuli, in order to evaluate the way in which this can be affected by various analgesics via their effects on the affective component of pain.

Practical answers to important research questions

  • Does our compound have analgesic properties?

    Using PainCart, we can study the analgesic potential of a new compound in healthy subjects. We can also compare the compound’s PainCart profile to profiles obtained with registered analgesics, and we can obtain important information regarding how the test compound affects the various mechanisms represented in PainCart as well as the subjective drug effects in human subjects.

  • What is the compound’s target population?

    Comparing the compound’s PainCart profile with the profile of well-known analgesics can help guide future studies in patients. For example, if the compound’s profile is similar to ibuprofen, its target population will differ from patients who are helped primarily by other analgesics such as pregabalin and morphine. Using this approach, our pain models can help researchers identify the patients who will most likely be helped.

  • Is our compound primarily active in the central or peripheral nervous system?

    Several key mechanisms are involved in processing pain. Using the nociceptive tasks included in PainCart ‒ for example, temporal summation in the electrical burst paradigm and the conditioned pain modulation response ‒ can provide important insight into whether a compound is more effective at targeting peripheral pain, central pain, or both.

  • Can PainCart be used to measure the effects of a compound designed to target neuropathic pain?

    When a subject perceives pain, central pain processing mechanisms are involved, even though the nociceptive stimulus is peripherally induced. Because PainCart includes both nociceptive and hyperalgesic pain models, a compound's PainCart profile can be used to measure the possible analgesic effects of compounds that act on the CNS.

  • In addition to analgesia, does the compound have other CNS effects?

    CHDR has extensive experience studying the effects of drugs on the central nervous system using NeuroCart®, our neurophysiological and cognitive test battery. By combining NeuroCart and PainCart in the same study, we can learn more about a compound’s analgesic potential, as well as identify possible effects on the CNS. For example, we can both identify and quantify the drug’s effects on alertness, body stability, and subjective drug-related effects such as feeling high.

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