Effects of Thrust Magnitude and Duration on Immediate Postspinal Manipulation Trunk Muscle Spindle Responses.

OBJECTIVE: The purpose of this study was to characterize trunk muscle spindle responses immediately after high-velocity, low-amplitude spinal manipulation (HVLA-SM) delivered at various thrust magnitudes and thrust durations. METHODS: Secondary analysis from multiple studies involving anesthetized adult cats (N = 70; 2.3-6.0 kg) receiving L6 HVLA-SM. Muscle spindle afferent recordings were obtained from L6 dorsal rootlets before, during, and immediately after HVLA-SM. L6 HVLA-SM was delivered posteriorly-to-anteriorly using a feedback motor with peak thrust magnitudes of 25%, 55%, and 85% of cat body weight (BW) and thrust durations of 25, 50, 75, 100, 150, 200, and 250 ms. Time to the first action potential and muscle spindle discharge frequency at 1 and 2 seconds post-HVLA-SM were determined. RESULTS: A significant association between HVLA-SM thrust magnitude and immediate (≤2 s) muscle spindle response was found (P < .001). For non-control thrust magnitude, pairwise comparisons (25%, 55%, 85% BW), 55% BW thrust magnitude had the most consistent effect on immediate post-HVLA-SM discharge outcomes (false discovery rate < 0.05). No significant association was found between thrust duration and immediate post-HVLA-SM muscle spindle response (P > .05). CONCLUSION: The present study found that HVLA-SM thrust magnitudes delivered at 55% BW were more likely to affect immediate (≤2 s) post-HVLA-SM muscle spindle response.

Effect of Denervation on XBP1 in Skeletal Muscle and the Neuromuscular Junction.

Denervation of skeletal muscle is a debilitating consequence of injury of the peripheral nervous system, causing skeletal muscle to experience robust atrophy. However, the molecular mechanisms controlling the wasting of skeletal muscle due to denervation are not well understood. Here, we demonstrate that transection of the sciatic nerve in Sprague-Dawley rats induced robust skeletal muscle atrophy, with little effect on the neuromuscular junction (NMJ). Moreover, the following study indicates that all three arms of the unfolded protein response (UPR) are activated in denervated skeletal muscle. Specifically, ATF4 and ATF6 are elevated in the cytoplasm of skeletal muscle, while XBP1 is elevated in the nuclei of skeletal muscle. Moreover, XBP1 is expressed in the nuclei surrounding the NMJ. Altogether, these results endorse a potential role of the UPR and, specifically, XBP1 in the maintenance of both skeletal muscle and the NMJ following sciatic nerve transection. Further investigations into a potential therapeutic role concerning these mechanisms are needed.

Role for Endocannabinoids in Spinal Manipulative Therapy Analgesia?

Chronic pain is quite prevalent and causes significant disabilities and socioeconomic burdens. Spinal manipulative therapy and other manipulative therapies are used to manage chronic pain. There is a critical knowledge gap about mechanisms and sites of action in spinal manipulative therapy pain relief, especially the short-term analgesia that occurs following a treatment. Endocannabinoids are an activity-dependent neurotransmitter system that acts as a short-term synaptic circuit breaker. This review describes both clinical research and basic research evidence suggesting that endocannabinoids contribute to short-term manipulative therapy analgesia. Determining endocannabinoids involvement in spinal manipulative therapy will improve its clinical efficacy when results from basic science and clinical research are translated.

Spinal manipulative therapy reduces peripheral neuropathic pain in the rat.

Spinal manipulative therapy, including low-velocity variable-amplitude spinal manipulation (LVVA-SM), relieves chronic low back pain, especially in patients with neuropathic radiating leg pain following peripheral nervous system insult. Understanding the underlying analgesic mechanisms requires animal models. The aim of the current study was to develop an animal model for the analgesic actions of LVVA-SM in the setting of peripheral neuropathic pain. Adult male Sprague-Dawley rat sciatic nerve tibial and common peroneal branches were transected, sparing the sural branch (spared nerve injury, SNI). After 15-18 days, rats were assigned randomly to one of three groups (n=9 each group): LVVA-SM at 0.15-or 0.16-Hz or Control. LVVA-SM (20° flexion at the L5 vertebra with an innovative motorized treatment table) was administered in anesthetized rats for 10 min. Control rats were administered anesthesia and positioned on the treatment table. After 10, 25, and 40 min, the plantar skin of the hindpaw ipsilateral to SNI was tested for mechanical sensitivity (paw withdrawal threshold to a logarithmic series of Semmes-Weinstein monofilaments) and cold sensitivity (duration of paw lifting, shaking, and/or licking to topical acetone application). SNI produced behavioral signs of mechanical and cold allodynia. LVVA-SM reduced mechanical, but not cold, hypersensitivity compared with Control (0.15-Hz: P=0.04 at 10 min; 0.16-Hz: P<0.001 at 10 min, P=0.04 at 25 min). The analgesic effect of LVVA-SM in chronic low back pain patients with neuropathic leg pain can be reverse-translated to a rat model Video abstract: http://links.lww.com/WNR/A453.

Neural Responses to Physical Characteristics of a High-velocity, Low-amplitude Spinal Manipulation: Effect of Thrust Direction.

STUDY DESIGN: Electrophysiological recordings were obtained from proprioceptors in deep lumbar paraspinal muscles of anesthetized cats during high-velocity low-amplitude spinal manipulation (HVLA-SM). OBJECTIVE: To determine how thrust direction of an HVLA-SM affects neural input from back musculature. SUMMARY OF BACKGROUND DATA: A clinician's ability to apply the thrust of an HVLA-SM in a specified direction is considered an important component of its optimal delivery. However, previous biomechanical studies indicate that the shear force component of the thrust vector is not actually transmitted to paraspinal tissues deep to the thoracolumbar fascia because the skin-fascia interface is frictionless. METHODS: Neural activity from muscle spindles in the multifidus and longissimus muscles was recorded from L6 dorsal rootlets in 18 anesthetized cats. After preload to the spinal tissues, HVLA-SMs (100-ms thrust duration) were applied through the intact skin overlying the L6 lamina. Thrusts were applied at angles oriented perpendicularly to the back and obliquely at 15° and 30° medialward or cranialward using a 6 × 6 Latin square design with three replicates. The normal force component was kept constant at 21.3 N. HVLA-SMs were preceded and followed by simulated spinal movement applied to the L6 vertebra. Changes in mean instantaneous discharge frequency (ΔMIF) of muscle spindles were determined both during the thrust and spinal movement. RESULTS: ΔMIFs during the HVLA-SM thrust were significantly greater in response to all thrust directions compared with the preload alone, but there was no difference in ΔMIF for any of the thrust directions during the HVLA-SM. HVLA-SM decreased some of the responses to simulated spinal movement but thrust direction had no effect on these changes. CONCLUSION: The shear force component of an HVLA-SM's thrust vector is not transmitted to the underlying vertebra sufficient to activate muscle spindles of the attached muscles. Implications for clinical practice and clinical research are discussed. LEVEL OF EVIDENCE: N/A.

Decreased spontaneous activity and altered evoked nociceptive response of rat thalamic submedius neurons to lumbar vertebra thrust.

The thalamus is a central structure important to modulating and processing all mechanoreceptor input destined for the cortex. A large number of diverse mechanoreceptor endings are stimulated when a high velocity low amplitude thrust is delivered to the lumbar spine during spinal manipulation. The objective of this study was to determine if a lumbar thrust alters spontaneous and/or evoked nociceptive activity in medial thalamic submedius (Sm) neurons. Extracellular recordings were obtained from 94 thalamic Sm neurons in 54 urethane-anesthetized adult Wistar rats. Spontaneous activity was recorded 5 min before and after an L5 control (no thrust) and thrust (85% rat body weight; 100 ms) procedure. In a subset of responsive nociceptive-specific neurons, mean changes in noxious-evoked response (10-s pinch with clip; 795 g) at three sites (tail, contra- and ipsilateral hindpaw) were determined following an L5 thrust. Mean changes in Sm spontaneous activity (60 s bins) and evoked noxious response were compared using a mixed model repeated measures ANOVA with Bonferroni post hoc t tests and paired t tests, respectively. Compared to control, spontaneous Sm activity decreased 180-240 s following the lumbar thrust (p < 0.005). Inhibitory evoked responses were attenuated in the contralateral hindpaw following an L5 thrust compared to control (p < 0.05). No other changes in spontaneous or noxious-evoked Sm activity were found. A delayed, but prolonged suppression of spontaneous Sm activity along with changes in noxious-evoked inhibitory responses in the contralateral hindpaw following lumbar vertebra thrust suggest that thalamic submedius neurons may play a role in central pain modulation related to manual therapy intervention.

Characteristics of Paraspinal Muscle Spindle Response to Mechanically Assisted Spinal Manipulation: A Preliminary Report.

OBJECTIVES: The purpose of this preliminary study is to determine muscle spindle response characteristics related to the use of 2 solenoid powered clinical mechanically assisted manipulation (MAM) devices. METHODS: L6 muscle spindle afferents with receptive fields in paraspinal muscles were isolated in 6 cats. Neural recordings were made during L7 MAM thrusts using the Activator V (Activator Methods Int. Ltd., Phoenix, AZ) and/or Pulstar (Sense Technology Inc., Pittsburgh, PA) devices at their 3 lowest force settings. Mechanically assisted manipulation response measures included (a) the time required post-thrust until the first action potential, (b) differences in mean frequency (MF) and mean instantaneous frequency (MIF) 2 seconds before and after MAM, and (c) the time required for muscle spindle discharge (MF and MIF) to return to 95% of baseline after MAM. RESULTS: Depending on device setting, between 44% to 80% (Pulstar) and 11% to 63% (Activator V) of spindle afferents required >6 seconds to return to within 95% of baseline MF values; whereas 66% to 89% (Pulstar) and 75% to 100% (Activator V) of spindle responses returned to within 95% of baseline MIF in <6 seconds after MAM. Nonparametric comparisons between the 22 N and 44 N settings of the Pulstar yielded significant differences for the time required to return to baseline MF and MIF. CONCLUSION: Short duration (<10 ms) MAM thrusts decrease muscle spindle discharge with a majority of afferents requiring prolonged periods (>6 seconds) to return to baseline MF activity. Physiological consequences and clinical relevance of described MAM mechanoreceptor responses will require additional investigation.

Antinociceptive Effects of Spinal Manipulative Therapy on Nociceptive Behavior of Adult Rats during the Formalin Test.

Optimizing pain relief resulting from spinal manipulative therapies, including low velocity variable amplitude spinal manipulation (LVVA-SM), requires determining their mechanisms. Pain models that incorporate simulated spinal manipulative therapy treatments are needed for these studies. The antinociceptive effects of a single LVVA-SM treatment on rat nociceptive behavior during the commonly used formalin test were investigated. Dilute formalin was injected subcutaneously into a plantar hindpaw. Licking behavior was video-recorded for 5 minutes. Ten minutes of LVVA-SM at 20° flexion was administered with a custom-made device at the lumbar (L5) vertebra of isoflurane-anesthetized experimental rats (n = 12) beginning 10 minutes after formalin injection. Hindpaw licking was video-recorded for 60 minutes beginning 5 minutes after LVVA-SM. Control rats (n = 12) underwent the same methods except for LVVA-SM. The mean times spent licking the formalin-injected hindpaw of both groups 1-5 minutes after injection were not different. The mean licking time during the first 20 minutes post-LVVA-SM of experimental rats was significantly less than that of control rats (P < 0.001). The mean licking times of both groups during the second and third 20 minutes post-LVVA-SM were not different. Administration of LVVA-SM had a short-term, remote antinociceptive effect similar to clinical findings. Therefore, mechanistic investigations using this experimental approach are warranted.

Neural Response During a Mechanically Assisted Spinal Manipulation in an Animal Model: A Pilot Study.

INTRODUCTION: Mechanoreceptor stimulation is theorized to contribute to the therapeutic efficacy of spinal manipulation. Use of mechanically-assisted spinal manipulation (MA-SM) devices is increasing among manual therapy clinicians worldwide. The purpose of this pilot study is to determine the feasibility of recording in vivo muscle spindle responses during a MA-SM in an intervertebral fixated animal model. METHODS: Intervertebral fixation was created by inserting facet screws through the left L5-6 and L6-7 facet joints of a cat spine. Three L6muscle spindle afferents with receptive fields in back muscles were isolated. Recordings were made during MA-SM thrusts delivered to the L7 spinous process using an instrumented Activator IV clinical device. RESULTS: Nine MA-SM thrusts were delivered with peak forces ranging from 68-122N and with thrust durations of less than 5ms. High frequency muscle spindle discharge occurred during MA-SM. Following the MA-SM, muscle spindle responses included returning to pre-manipulation levels, slightly decreasing for a short window of time, and greatly decreasing for more than 40s. CONCLUSION: This study demonstrates that recording in vivo muscle spindle response using clinical MA-SM devices in an animal model is feasible. Extremely short duration MA-SM thrusts (<5ms) can have an immediate and/or a prolonged (> 40s) effect on muscle spindle discharge. Greater peak forces during MA-SM thrusts may not necessarily yield greater muscle spindle responses. Determining peripheral response during and following spinal manipulation may be an important step in optimizing its' clinical efficacy. Future studies may investigate the effect of thrust dosage and magnitude.

Effect of spinal manipulation thrust magnitude on trunk mechanical activation thresholds of lateral thalamic neurons.

OBJECTIVES: High-velocity low-amplitude spinal manipulation (HVLA-SM), as performed by doctors who use manual therapy (eg, doctors of chiropractic and osteopathy), results in mechanical hypoalgesia in clinical settings. This hypoalgesic effect has previously been attributed to alterations in peripheral and/or central pain processing. The objective of this study was to determine whether thrust magnitude of a simulated HVLA-SM alters mechanical trunk response thresholds in wide dynamic range (WDR) and/or nociceptive specific (NS) lateral thalamic neurons. METHODS: Extracellular recordings were carried out in the thalamus of 15 anesthetized Wistar rats. Lateral thalamic neurons having receptive fields, which included the lumbar dorsal-lateral trunk, were characterized as either WDR (n=22) or NS (n=25). Response thresholds to electronic von Frey (rigid tip) mechanical trunk stimuli were determined in 3 directions (dorsal-ventral, 45° caudalward, and 45° cranialward) before and immediately after the dorsal-ventral delivery of a 100-millisecond HVLA-SM at 3 thrust magnitudes (control, 55%, 85% body weight). RESULTS: There was a significant difference in mechanical threshold between 85% body weight manipulation and control thrust magnitudes in the dorsal-ventral direction in NS neurons (P=.01). No changes were found in WDR neurons at either HVLA-SM thrust magnitude. CONCLUSIONS: This study is the first to investigate the effect of HVLA-SM thrust magnitude on WDR and NS lateral thalamic mechanical response threshold. Our data suggest that, at the single lateral thalamic neuron level, there may be a minimal spinal manipulative thrust magnitude required to elicit an increase in trunk mechanical response thresholds.

Introducing the external link model for studying spine fixation and misalignment: current procedures, costs, and failure rates.

OBJECTIVE: This is the last article in a series of 3 articles introducing a new animal model, the external link model (ELM), that permits reversible, nontraumatic control of the cardinal biomechanical features of the subluxation: fixation and misalignment. A detailed description of current ELM procedures is presented and practical issues are reviewed such as expense (dollars and time) and construct failure rates during and after the surgical implant procedure. METHOD: Descriptive report of current ELM procedures, refinements to the spinous attachment units (SAUs), and tabulation of costs and failure rates drawn from recent studies. RESULTS: In contrast to the older, 1-piece stainless steel SAUs, new 3-piece titanium SAUs may be reimplanted many times without failure. Consequently, the cost per ELM ranges from $579 to $69, depending on whether the SAUs, links, and screws must be purchased or are already available for implanting. The SAU implant procedure requires between 0.5 and 1.25 hours, depending on the experience of the surgeon. The total construct failure rate for the ELM is 24.2% (6.6% at surgery failure + 17.8% postsurgery failures). This rate is consistent with that reported in spine implant studies with other devices. To date, more than 500 male Sprague-Dawley rats (350-450 g) have been implanted with SAUs for ELM studies at the Palmer Center for Chiropractic Research and the National University of Health Sciences. CONCLUSION: It has been our experience that individuals with basic animal research training will become proficient at producing the ELM after observing 3 to 4 implant procedures and performing 4 to 6 procedures on their own.