Proprioceptive mechanisms underlying post-spinal manipulation response in an NGF-induced low back pain model

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Abstract. Low back pain (LBP) is a major health problem in the United States costing annually over $50 billion in treatment-related costs and $100 billion in indirect costs (i.e. lost productivity). This national health crisis is further compounded by a recent over-reliance on prescription opioids for therapeutic pain management. High velocity low amplitude spinal manipulation (HVLA-SM) is a non-pharmacological LBP approach recommended by a majority of clinical practice guidelines. However, a lack of knowledge concerning underlying neurophysiological mechanisms hinders wider clinical acceptance, usage, and optimization of this therapeutic approach. Proposed mechanisms of HVLA-SM efficacy include changes in muscle spindle sensitivity related to rapid stretch-induced stimulation of mechanoreceptors in muscle and/or other trunk tissues. Previous work in our lab has shed light on the relationship between the mechanical characteristics of HVLA-SM (thrust duration, thrust amplitude, thrust rate, preload magnitude & duration, and thrust contact site) and trunk muscle spindle afferent responsiveness in non-chemosensitized environments. Recently pilot studies using commercially available HVLA-SM devices with extremely short thrust durations of 2-3ms revealed a dichotomy among post-HVLA-SM return to baseline muscle spindle discharge. Distinct subpopulations of spindle afferents returned to baseline discharge post-HVLA-SM relatively rapidly (<2s), while others required substantially longer periods (>10s), which far outlasted the mechanical stimulus of HVLA-SM. The biological and/or biomechanical factors responsible for this post-HVLA-SM response dichotomy, as well as whether or not clinically relevant tissue chemosensitization acts to maximize these dichotomous post-HVLA-SM responses is currently unknown. A recently developed preclinical LBP model has been established using a translationally relevant pain molecule, nerve growth factor (NGF). NGF is a neurotrophin associated with pain which is naturally upregulated after muscle damage, inflammation, and/or peripheral nerve injury. Injection of NGF into deep trunk musculature creates persistent (days/weeks), localized trunk hyperalgesia by sensitizing skeletal muscle nociceptors and producing marked spinal dorsal horn neuron hyperexcitability; both of which are thought to be key components of LBP chronicity. This proposal will characterize post-HVLA-SM muscle spindle response based on intrafusal fiber classification, HVLA-SM thrust duration (2-3ms vs 100ms), and HVLA-SM peak biomechanical forces reaching deep spinal tissues (multifidus muscle) in control and trunk chemosensitized (NGF-induced LBP) environments in order to reveal neurophysiological mechanisms underlying spinal manipulation and to establish another preclinical NGF-induced LBP model so as to better inform and/or optimize this non-pharmacological approach to LBP.