Beyond biopsychosocial: The keystone mechanism theory of pain.

Pain is a deeply personal experience, with interindividual differences in its chronification and treatment presenting a formidable healthcare challenge. The biopsychosocial model (BPSm) has been hugely influential within nascent attempts at precision pain medicine, steering the field away from a reductionist biomechanical viewpoint and emphasising complex interactions of biological, psychological, and social factors which shape the individuality of pain. However, despite offering a strong theoretical foundation and holistic perspective, we contend that the BPSm remains limited in its capacity to deliver truly mechanistically informed treatment of pain. We therefore propose the keystone model of pain which offers a pragmatic balance between the dimensionality expansive BPSm and overly reductive approaches, providing both theoretical and practical advantages for the transition from treating populations to individual people.

Introduction to the EQIPD quality system.

While high risk of failure is an inherent part of developing innovative therapies, it can be reduced by adherence to evidence-based rigorous research practices. Supported through the European Union's Innovative Medicines Initiative, the EQIPD consortium has developed a novel preclinical research quality system that can be applied in both public and private sectors and is free for anyone to use. The EQIPD Quality System was designed to be suited to boost innovation by ensuring the generation of robust and reliable preclinical data while being lean, effective and not becoming a burden that could negatively impact the freedom to explore scientific questions. EQIPD defines research quality as the extent to which research data are fit for their intended use. Fitness, in this context, is defined by the stakeholders, who are the scientists directly involved in the research, but also their funders, sponsors, publishers, research tool manufacturers, and collaboration partners such as peers in a multi-site research project. The essence of the EQIPD Quality System is the set of 18 core requirements that can be addressed flexibly, according to user-specific needs and following a user-defined trajectory. The EQIPD Quality System proposes guidance on expectations for quality-related measures, defines criteria for adequate processes (i.e. performance standards) and provides examples of how such measures can be developed and implemented. However, it does not prescribe any pre-determined solutions. EQIPD has also developed tools (for optional use) to support users in implementing the system and assessment services for those research units that successfully implement the quality system and seek formal accreditation. Building upon the feedback from users and continuous improvement, a sustainable EQIPD Quality System will ultimately serve the entire community of scientists conducting non-regulated preclinical research, by helping them generate reliable data that are fit for their intended use.

Effects of Spinal Cord and Peripheral Nerve Stimulation Reflected in Sensory Profiles and Endogenous Pain Modulation.

OBJECTIVES: Spinal cord and peripheral nerve stimulation (SCS/PNS) may alleviate chronic pain; however, the underlying mechanisms remain controversial. The aim of this observational study was to assess sensory changes in the ON-conditions and OFF-conditions to obtain insights into the mechanism of analgesic effects of SCS/PNS. MATERIALS AND METHODS: We contacted 85 patients and selected 28 patients with sufficient pain relief by SCS (n=15) or PNS (n=13) to assess their ongoing pain intensity (Numerical Rating Scale, 0 to 10), pain thresholds using Quantitative Sensory Testing (DFNS-protocol), and conditioned pain modulation (CPM) in a nonrandomized manner 2 to 4 hours after SCS/PNS deactivation (OFF-condition) and during stimulation (ON-condition). For each patient, the number of abnormally decreased pain thresholds, the presence of dynamic mechanical allodynia, and/or increased pain sensitivity was additionally totaled OR summed. RESULTS: In the ON-condition, pain intensity decreased (Numerical Rating Scale SCS: 6.5±2.1 vs. 3.7±2.3, P<0.01; PNS: 6.2±1.4 vs. 4±1.9, P<0.01), but this did not correlate with any single sensory parameter. However, for SCS, the total number of parameters indicating hyperalgesia was significantly reduced in the ON-condition (45 vs. 23, P=0.001). A smaller CPM effect in the OFF-condition correlated with a greater CPM improvement during stimulation (SCS: r=-0.741, P=0.002; PNS: r=-0.773, P=0.003), independently from the spontaneous pain intensity. DISCUSSION: The analgesic effect of SCS/PNS did not correlate with changes of single sensory parameters, but SCS/PNS reduced the number of abnormal hyperalgesic findings disregarding the kind of applied stimuli, suggesting a general antihyperalgesic effect. In addition, stimulation improved the endogenous pain inhibition. Both findings indicate that SCS/PNS may modulate central circuits.