Another approach to improve our understanding of CRPS will be discussed today. A large group of CRPS Patients (n=612) were examined by means of the DFNS QST protocol and analyzed with two separate hypothesis-free cluster analyses (Dilara Kersebaum). Training (n=386) and validation set (n=226) identified and confirmed three distinct sensory phenotypes (hyperalgesia n=387, loss of sensation n=203, and strong allodynia and hyperalgesia n=22), respectively. These findings might well support stratification strategies in upcoming clinical studies (II-B2.W.02).
Naturally occurring neurotoxic peptides are gaining increasing interest in the treatment of chronic pain. Botulinum neurotoxin A (BoNT-A) is approved clinically for the treatment of non-pain indications and there is plenty data available suggesting efficacy in several pain indications, including neuropathic and inflammatory pain. In a therapeutic approach rats with anterior cruciate ligament transection, a clinically relevant model of OA, were treated intra-articular with BoNT-A. Clear improvement in static weight bearing was demonstrated 20 weeks later. Furthermore, chondrocytes (ATDC5 cells) were analyzed by means of RT-PCR 21 days after BoNT-A treatment suggesting involvement of the rho signaling pathway (Pei Chun Hsieh et al., II-D-78). Prophylactic treatment with BoNT-A of rats which received unilateral intraplantar CFA 24 hours later resulted in improved dynamic weight bearing. Reduced IL-1ß and TNF-α levels as measured by qPCR were detected in the inflamed hind paws, suggesting a potential anti-inflammatory contribution (Jens Nagel et al., II-D-85). How do all this data translate into patients? Regarding neuropathic pain, several clinical trials have been published but were limited in size and design. Nadine Attal and colleagues are performing a large phase 2 proof-of-concept clinical trial with ≥120 patients suffering from moderate to severe PNP (PHN or PSNP). This 20-weeks study which will include bedside QST is considered of high relevance for translating the preclinical efficacy of BoNT-A into clinical setting (II-D2.W.10).
Early detection and adequate treatment are crucial for many pain types. Denis Dupoiron and colleagues present data on patients with PSNP after breast cancer surgery comparing pregabalin with high concentration capsaicin patch (HCCP). Both treatments were efficacious. However, HCCP seems to be a preferred alternative to pregabalin since more than 50% of patients switched from pregabalin to HCCP after two months while no patient switched from HCCP to pregabalin (II-D2.W.03). Repeated HCCP treatment confirmed increased efficacy (II-D-76). More data on repeated HCCP treatment is shown by Marielle Eerdekens. Patients suffering from PHN (II-D2.W.04) and PNI (II-D-75) experienced improved pain relief upon 4 treatment cycles. Nevertheless, HCCP treatment comes with strong nociceptive pain during treatment procedure and local anesthesia is recommended to ameliorate this pain. Anna Maria Kiernan and colleagues present data on the use of Augmented Reality which was able to reduce acute pain during HCCP treatment (II-D-28).
How can patient-relevant endpoints be better measured in times when reimbursement of novel drugs increasingly depends on (international) HTA procedures? Danielle Huisman and colleagues present data adding to a long list of examples of poor communication between patients and clinicians. Here, analysis of patients’ and clinicians’ views on pain in IBD reveals room for improvement on both sides. Once again, these data show that there is still a long way to go and education on pain management needs to continue to develop a solid basis for a common understanding (II-B.10).
