Translational Pain Biomarkers

Translational Pain Biomarkers

Chairman: Lars Arendt-Nielsen, Professor (LAN)

Objective

To develop mechanistic, quantitative, translational pain biomarkers for pre-clinical, human experimental, and clinical pain research and to apply sophisticated techniques to mechanistically profile both chronic pain patients and new analgesic compounds under development (early clinical trial phases I and II ).

Research Strategy

Mechanistic, quantitative, translational human pain biomarkers have proven to be sensitive in detecting specific mechanisms underlying certain pain conditions applicable both in animals and humans. Furthermore, translational biomarkers should predict the analgesic/anti-nociceptive effects of drugs in both pre-clinical and clinical phases in a bi-directional translational manner.

Pain biomarkers are used individually or combined in platforms to establish individualized profiling of pain patients (prognostic/diagnostic biomarkers) and/or to identify specific mode-of-action and responders for optimal pain treatments (personalized pain medicine).

Advanced profiling consists of standardized activation of pain pathways followed by quantitative psychophysical, electrophysiological, imaging or biochemical assessments of the ongoing and paroxysmal pain and evoked pain responses. Thus, a given pathology or pharmacological activity can be identified based on the pathways or mechanisms affected. Based on preclinical profiles of standardized pathologies or analgesics, a platform of translational pain tests can be developed and applied, both in healthy volunteers and pain patients and before/after pharmacological interventions. This mechanistic approach is not limited to new drugs but can also be utilized for profiling existing analgesics with mechanisms of action that are not clearly identified.

The research focuses on finding ways or developing and validating surrogate models that may act as proxies for clinical pain conditions to differentiate peripheral and central pain mechanisms to investigate which mechanisms are being modulated by different classes of analgesics and to select the most adequate patient population and outcome parameters for an optimal clinical trial design.

Areas of specific translational interest are investigating the possible roles of glial cell-induced hypersensitivity, contribution of neuroimmunology in chronic pain, identification and assessment of key processes, and possible drug candidates capable of targeting or modulating the reactions.

The strategies pursued for the development and application of new advanced multi-modal, multi-tissue, mechanistic pain biomarker platforms for diagnostics and drug profiling include but not limited to:

  1. Standardized activation of modality specific nociceptive Aδ and C-afferents
  2. Standardized activation of modality-specific nociceptive afferents from different structures (e.g., skin, muscles, fascia, joints, viscera)
  3. Standardized activation of specific pain mechanisms (e.g., temporal/spatial summation; descending inhibition, cortical reorganization, inflammatory processes)
  4. Standardized experimental induction of hyperexcitable stages in peripheral and central neural structures (surrogate models)
  5. Standardized activation of modality-specific non-nociceptive afferents from different structures under hyperexcitable stages (experimental, clinical)
  6. Quantitative recordings of the evoked responses (e.g., psychophysics, electrophysiology, bio-chemical, imaging)
  7. Tissue or pathology specific biochemical markers (e.g., serological markers, genetics-genomics-proteomics)

A common goal is to generate knowledge, skills, and competences for developing clinically applicable regimes for individualized/personalized pain medicine.

Teaching and Training

Training programs associated with translational medicine are available for Post Docs, PhD students (on stipend or self-funded) (Ph.D. School) and undergraduate in Medicine with industrial Specialization, Translational Medicine Profile (School of Medicine and Health). Visiting scholars, exchange students, and guest researchers (self-funded) are also accepted. Many relevant projects in the field are established in collaboration with national and international institutions and pharmaceutical industries.

Innovation

An extensive network of collaborations exists with medtech and pharmaceutical industries worldwide. Spinout companies are established (e.g., C4Pain and NociTech) and patents are filed in the field of pain assessment technologies. Collaborations on design and execution of early clinical trial utilizing a mechanistic approach are also established.
The unique competences and the preparedness for research-based innovation in collaboration with industry is marked via the Health Science and Technology Business Park (Eir) hosted by SMI.

Laboratories