A role for animal research relevant to yoga

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In order for a new behavioral practice or therapy to be fully approved and implemented into modern society’s institutions, policymakers require evidence of the safety and efficacy of that practice that must be provided by a critical mass of numerous robust and rigorous research trials. Furthermore, in addition to the determination of safety and efficacy, there is also the need for the elucidation of the underlying mechanisms behind any new practice. This provides policymakers with more assurance of the predictability and safety of a practice, especially with regard to potential side effects or interactions with other practices or therapies. It also provides information useful for the potential modification and adaptation of these practices to different populations such as children, the elderly, and patients with varying diseases. This is exemplified by federal regulatory agencies that are responsible for pharmaceutical approvals who require evidence for a drug’s mechanism of action to ensure its efficacy and safety before approving it for widespread use in the population. We have made remarkable progress in the biomedical research on yoga and its component practices of asanas, pranayama, relaxation, and meditation demonstrating its safety and efficacy in a variety of populations including children/adolescents and as therapy.[1,2] We now also have a deeper and growing understanding of many of the mechanisms underlying each of these yoga practice components due to yoga research over the past few decades employing state-of-the-art scientific methodology with strong objective outcome measures. These include neuroimaging to determine the changes in neurophysiology and neuroplasticity in the brain and nervous system[3] and molecular biological and epigenetic techniques to document changes taking place at the cellular and molecular level.[4] However, research on behavioral practices in humans is always a complicated and challenging task due to the complexities of human behavior, specifically with respect to the serious confounds of expectation, belief, and placebo effects. In contrast, the advantage in drug development research is that preliminary studies in animal models provide substantial information on underlying mechanisms that informs how these agents may be working in humans. Unfortunately, animal models are not as applicable for understanding underlying mechanisms in human behavioral treatments, because animals cannot mimic complex behaviors such as those contributing to yoga. It is problematic to study meditation in rodents. Despite this substantial limitation, there are a few fields of psychophysiology relevant to yoga that can be studied in animals and can provide significant support for the underlying mechanisms of yoga. One of these is on the effects of asana practices, many of which involve stretching of the body, and the other is on the efficacy of pranayama practices, especially with respect to the core pranayama practice of slow breathing. Recent research on the role of the fascia, the syncytium of connective tissue that encompasses our internal muscles and organs, has revealed remarkable characteristics of its internal movement, its response to stretching, and its alteration in musculoskeletal conditions such as low back pain.[5] Early research used passive stretching manipulations in a rat model demonstrating positive changes in fascial functioning.[6] These passive stretching interventions yielded positive changes in inflammation, locomotion, mechanical sensitivity, and macrophage expression. There is now research on an active stretching porcine model showing changes in inflammatory markers.[7] More recently, an active stretching rodent manipulation has been evaluated in which mice underwent voluntary self-stretching and body elongation in order to access food and water.[8] The results of this study found that active stretching inhibited tumor growth and impacted systemic protein profiles. These animal studies are providing strong evidence for the underlying fascial mechanisms mediating the positive influence of stretching activities such as yoga asanas. The authors of these studies have been arguing for the relevance of this research to mind–body practices such as yoga and tai chi. Slow diaphragmatic breathing is a core and important yoga pranayama practice and is a mind–body practice with a strong history of basic research showing benefit in improving human physiology and in clinical trials research showing efficacy as a treatment for patient populations.[9,10] Two well-known claims in yoga are a) that slow breathing can lead to a reduction of stress, arousal and anxiety over both the short and long term, and b) that regular long-term slow breathing practice can lead to the slowing of spontaneous breathing rate. A human study providing evidence for the plasticity in spontaneous breath rate following long-term regular slow breathing practice showed a slowed respiratory frequency, slightly increased tidal volume, and prolonged exhale.[9] These effects on stress, arousal, and plasticity have now been confirmed in animal research. Using an operant conditioning model, researchers were able to demonstrate that rats could be conditioned to adopt a significantly slowed spontaneous respiration rate, and that conditioned rats showed reduced stress reactivity.[10] Research in the mouse has identified a key neuronal subpopulation of the preBötzinger complex in the brain, which is the primary generator of respiration. Furthermore, experimental manipulation of this complex has demonstrated that it has important involvement in the regulation of arousal level.[11] The implications for the value and application of yogic breathing practices for changing stress and arousal states are becoming clear and compelling. The June 2018 (Volume 19, No. 6) cover of the prestigious journal Nature Reviews depicts a mouse in meditative posture in Gyan Mudra with the cover text “Breathe in, Breath out; The Neural Control of Respiration,”[12] and the comprehensive review published in that issue elucidates the strong connections between respiration and arousal, cognitive function, and emotion.[13] More recently, a remarkable study published in the journal Nature Neuroscience used a comprehensive and elegant manipulation of the mouse respiratory center using optogenetic stimulation to either slow or increase breathing frequency to demonstrate a direct relationship between respiration rate and negative affect.[14] The value and relevance of this kind of animal research to understanding the underlying mechanisms of yoga practices are clear. A dismissal of the claims of yoga proponents of the efficacy of asana and pranayama practices based on placebo effect and other nonspecific behavioral confounds is becoming much less tenable. We are now standing on stronger scientific ground with respect to research on the benefits of asana and pranayama, at least for the stretching and breathing frequency aspects of these practices. Perhaps, it is not inconceivable that there could also someday be research on credible animal models of the meditation and relaxation aspects of yoga practice. The articles featured in this issue reflect the growing scientific engagement with yoga and integrative health across clinical, psychological, and philosophical domains. Together, they highlight the therapeutic potential of yoga-based interventions in diverse populations while emphasizing methodological rigor and interdisciplinary perspectives. Bharti Patel and Biman Bihari Paul, in their study “Feasibility and Preliminary Effects of a 12-Week Integrated Yoga Module on Physical and Psychosocial Health in Patients with Relapsing-Remitting Multiple Sclerosis,” report that an integrated yoga intervention is feasible and well-accepted, with promising improvements in physical functioning and psychosocial well-being. The findings support yoga as a complementary approach in neurorehabilitation, warranting

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