No pain no gain: Exploration and validation of experimental pain models in human healthy volunteers for applications in drug development and implications of quantitative sensory testing in neuropathic pain patients

Pain management is a major challenge for modern medicine. It is estimated that the prevalence of chronic pain could be as high as 35 %. This means that 1 in 3 people will experience a period with chronic pain during their lives. This burden on society underlines the importance of developing effective analgesic therapies. As a hypothesis we tested if Quantitative Sensory Testing (QST) measures for acute and neuropathic pain in healthy volunteers and patients would improve the reliability of efficacy studies. Furthermore we aimed to develop a robust topical capsaicin model for neuropathic pain to achieve reliable hyperalgesia and allodynia. Our results showed that the heat pain threshold, the pressure pain threshold and the cold pressor test are reliable measures to test analgesic efficacy in acute pain. In general the high test-retest reliability in our studies supports the use of a standardized QST battery in for testing novel analgesics and can improve assay sensitivity of clinical trials. Furthermore, our QST database demonstrated that many patients with chronic pain not only have abnormal somatosensory functioning at their painful pathological body side but also on the contralateral (non-painful) body side. Also, our Heat Capsaicin Warmth (HCW) model for neuropathic pain using continuous pain with capsaicin cream combined with continuous warmth demonstrated that this is a reliable method to induce allodynia, a key symptom of neuropathic pain. Overall the results from our studies can contribute to the selection of appropriate pain tests and models and can improve clinical trials for pain treatments.