Technologies to investigate the mechanisms of force-based manipulations: a narrative methods review

Force-based manipulations (FBM), as defined by the National Center for Complementary and Integrative Health (NCCIH), involve the passive application of mechanical force to the body with therapeutic intent. These approaches are commonly used in pain management, rehabilitation, wellness, and disease prevention, and include spinal and extremity manipulation, mobilization, soft tissue manipulation, massage, myofascial release, osteopathic manipulative treatment, and related manual or instrument-assisted therapies. FBM may involve light touch, pressure, mobilization, thrust, adjustment, needling, or other mechanically mediated inputs, and their effects may be influenced by contextual factors, including interpersonal relational dynamics, physical environment and patient psychophysics. Consistent with ongoing interprofessional efforts to standardize manual therapy nomenclature, this review emphasizes the careful descriptive terminologies and mechanical parameters rather than profession-specific labels. Although these therapeutic approaches are widely used to manage pain and improve function, the biological processes associated with FBM remain unknown and/or inadequately characterized. This narrative review synthesizes established technologies for investigating FBM across multiple domains, including biomechanical loading and motion analysis, tissue, cellular, and molecular imaging, biomarker, transcriptomic, and mechanobiological assessment, neurophysiological monitoring, vascular and microcirculatory assessment, computational modeling/data science, sensory, psychophysical, and contextual assessment, and mechanistic perturbation and neuromodulation methods. Rather than focusing on individual techniques in isolation, this review organizes these methods within a multi-scale framework that relates externally applied mechanical inputs to measurable internal mechanical, neural, vascular, cellular, molecular, regional, and whole-organism responses. Crucially, the physiological impact of these mechanical events is continuously modulated by the operationalized environment and therapeutic alliance, which must be treated as measurable covariates that interact with mechanical inputs. By providing a structured overview of validated and accessible methodologies, this work offers a roadmap for mechanistic FBM research and supports the future development of integrative, interdisciplinary studies. This framework is intended to help investigators characterize applied mechanical inputs using shared descriptive terminology, evaluate physiological responses across levels of structure and function, and examine relationships among mechanical input, contextual factors, biological mechanisms, and clinically meaningful outcomes.