In vivo measurement of intradiscal pressure changes related to thrust and non-thrust spinal manipulation in an animal model: a pilot study.

BACKGROUND: The intervertebral disc is a known back pain generator and is frequently the focus of spinal manipulative therapy evaluation and treatment. The majority of our current knowledge regarding intradiscal pressure (IDP) changes related to spinal manual therapy involves cadaveric studies with their inherent limitations. Additional in vivo animal models are needed to investigate intervertebral disc physiological and molecular mechanisms related to spinal manipulation and spinal mobilization treatment for low back disorders. METHODS: Miniature pressure catheters (Millar SPR-1000) were inserted into either the L4-L5 or L5-L6 intervertebral disc of 3 deeply anesthetized adult cats (Oct 2012-May 2013). Changes in IDP were recorded during delivery of instrument-assisted spinal manipulation (Activator V® and Pulstar®) and motorized spinal flexion with/without manual spinous process contact. RESULTS: Motorized flexion of 30° without spinous contact decreased IDP of the L4-L5 disc by ~ 2.9 kPa, while physical contact of the L4 spinous process decreased IDP an additional ~ 1.4 kPa. Motorized flexion of 25° with L5 physical contact in a separate animal decreased IDP of the L5-L6 disc by ~ 1.0 kPa. Pulstar® impulses (setting 1-3) increased IDP of L4-L5 and L5-L6 intervertebral discs by ~ 2.5 to 3.0 kPa. Activator V® (setting 1-4) impulses increased L4-L5 IDP to a similar degree. Net changes in IDP amplitudes remained fairly consistent across settings on both devices regardless of device setting suggesting that viscoelastic properties of in vivo spinal tissues greatly dampen superficially applied manipulative forces prior to reaching deep back structures such as the intervertebral disc. CONCLUSIONS: This study marks the first time that feline in vivo changes in IDP have been reported using clinically available instrument-assisted spinal manipulation devices and/or spinal mobilization procedures. The results of this pilot study indicate that a feline model can be used to investigate IDP changes related to spinal manual therapy mechanisms as well as the diminution of these spinal manipulative forces due to viscoelastic properties of the surrounding spinal tissues. Additional investigation of IDP changes is warranted in this and/or other in vivo animal models to provide better insights into the physiological effects and mechanisms of spinal manual therapy at the intervertebral disc level.

Measurement of Force and Intramuscular Pressure Changes Related to Thrust Spinal Manipulation in an In Vivo Animal Model.

Current knowledge regarding biomechanical in vivo deep tissue measures related to spinal manipulation remain somewhat limited. More in vivo animal studies are needed to better understand the effects viscoelastic tissue properties (i.e., dampening) have on applied spinal manipulation forces. This new knowledge may eventually help to determine whether positive clinical outcomes are associated with particular force thresholds reaching superficial and/or deep spinal tissues. A computer-controlled feedback motor and a modified Activator V device with a dynamic load cell attached were used to deliver thrust spinal manipulations at various magnitudes to the L7 spinous process in deeply anesthetized animals. Miniature pressure catheters (Millar SPR-1000) were inserted unilaterally into superficial and deep multifidi muscles. Measurements of applied mechanical forces and superficial/deep multifidi intramuscular pressure changes were recorded during spinal manipulations delivered in vivo. Manipulative forces and net changes in intramuscular pressures reaching deep spinal tissues are greatly diminished by viscoelastic properties of in vivo tissues, which could have possible clinical safety and/or mechanistic implications.

Influence of Intervertebral Fixation and Segmental Thrust Level on Immediate Post-Spinal Manipulation Trunk Muscle Spindle Response in an Animal Model.

OBJECTIVE: To characterize the effect of unilateral (single and two-level) lumbar facet/zygapophysial joint fixation on paraspinal muscle spindle activity immediately following L4 or L6 high velocity low amplitude spinal manipulation (HVLA-SM) delivered at various thrust durations. METHODS: Secondary analysis of immediate (≤2 s) post-HVLA-SM trunk muscle spindle response from two studies involving anesthetized adult cats (n = 39; 2.3-6.0 kg) with either a unilateral single (L5/6) or two-level (L5/6 and L6/7) facet joint fixation. All facet fixations were contralateral to L6 dorsal root recordings. HVLA-SM was delivered to the spinous process in a posterior-to-anterior direction using a feedback motor with a peak thrust magnitude of 55% of average cat body weight and thrust durations of 75, 100, 150, and 250 ms. Time to 1st action potential and spindle activity during 1 and 2 s post-HVLA-SM comparisons were made between facet joint fixation conditions and HVLA-SM segmental thrust levels. RESULTS: Neither two-level facet joint fixation, nor HVLA-SM segmental level significantly altered immediate post-HVLA-SM spindle discharge at tested thrust durations (FDR > 0.05). CONCLUSIONS: Two-level facet joint fixation failed to alter immediate (≤2 s) post-HVLA-SM spindle discharge when compared to single-level facet joint fixation at any thrust duration. Segmental thrust level did not alter immediate post-HVLA-SM spindle response in two-level facet joint fixation preparations.

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.

The Neurophysiological Impact of Experimentally-Induced Pain on Direct Muscle Spindle Afferent Response: A Scoping Review.

Background: Musculoskeletal pain disorders are among the leading causes of years lived with disability worldwide representing a significant burden to society. Studies investigating a "nociceptive-fusimotor" relationship using experimentally-induced pain/noxious stimuli and muscle spindle afferent (MSA) response have been published over several decades. The purpose of this scoping review was to systematically identify and summarize research findings related to the impact of experimentally-induced pain or noxious stimulation on direct MSA discharge/response. Methods: PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane and Embase were searched from database inception to August 2020. Eligible studies were: (a) published in English; (b) clinical or pre-clinical studies; (c) original data studies; (d) included the investigation of MSA response to experimentally-induced pain or noxious stimulation; (e) included quantification of at least one direct physiological measure associated with MSA activity/response. Two-phase screening procedures were conducted by a pair of independent reviewers and data extracted from eligible studies. Results: The literature search resulted in 195 articles of which 23 met inclusion criteria. Six studies (26%) were classified as clinical and 17 (74%) as pre-clinical. Two clinical studies investigated the effects of sacral dermatome pin-pricking on MSA response, while the remaining 4 studies investigated the effects of tonic muscle and/or skin pain induced by injection/infusion of hypertonic saline into the tibialis anterior muscle or subdermal tissues. In pre-clinical studies, muscle pain was induced by injection of noxious substances or the surgical removal of the meniscus at the knee joint. Conclusion: Clinical studies in awake humans reported that experimentally-induced pain did not affect, or else slightly decreased MSA spontaneous discharge and/or response during weak dorsiflexor muscle contraction, thus failing to support an excitatory nociceptive-fusimotor relationship. However, a majority of pre-clinical studies indicated that ipsilateral and contralateral muscle injection of noxious substances altered MSA resting discharge and/or response to stretch predominately through static fusimotor reflex mechanisms. Methodological differences (use of anesthesia, stretch methodology, etc.) may ultimately be responsible for the discrepancies between clinical and pre-clinical findings. Additional investigative efforts are needed to reconcile these discrepancies and to clearly establish or refute the existence of nociceptive-fusimotor relationship in muscular pain.

Spinal Mobilization Prevents NGF-Induced Trunk Mechanical Hyperalgesia and Attenuates Expression of CGRP.

INTRODUCTION: Low back pain (LBP) is a complex and growing global health problem in need of more effective pain management strategies. Spinal mobilization (SM) is a non-pharmacological approach recommended by most clinical guidelines for LBP, but greater utilization and treatment optimization are hampered by a lack of mechanistic knowledge underlying its hypoalgesic clinical effects. METHODS: Groups of female Sprague-Dawley rats received unilateral trunk (L5 vertebral level) injections (50 µl) of either vehicle (phosphate-buffer solution, PBS; VEH) or nerve growth factor (NGF; 0.8 µM) on Days 0 and 5 with or without daily L5 SM (VEH, NGF, VEH + SM, VEH + SM). Daily passive SM (10 min) was delivered by a feedback motor (1.2 Hz, 0.9N) from Days 1 to 12. Changes in pain assays were determined for mechanical and thermal reflexive behavior, exploratory behavior (open field events) and spontaneous pain behavior (rat grimace scale). On Day 12, lumbar (L1-L6) dorsal root ganglia (DRG) were harvested bilaterally and calcitonin gene-related peptide (CGRP) positive immunoreactive neurons were quantified from 3 animals (1 DRG tissue section per segmental level) per experimental group. RESULTS: NGF induced bilateral trunk (left P = 0.006, right P = 0.001) mechanical hyperalgesia and unilateral hindpaw allodynia (P = 0.006) compared to the vehicle group by Day 12. Additionally, we found for the first time that NGF animals demonstrated decreased exploratory behaviors (total distance traveled) and increased grimace scale scoring compared to the VEH group. Passive SM prevented this development of local (trunk) mechanical hyperalgesia and distant (hindpaw) allodynia, and normalized grimace scale scores. NGF increased CGRP positive immunoreactive neurons in ipsilateral lumbar DRGs compared to the VEH group ([L1]P = 0.02; [L2]P = 0.007) and SM effectively negated this increase in pain-related neuropeptide CGRP expression. CONCLUSION: SM prevents the development of local (trunk) NGF-induced mechanical hyperalgesia and distant (hindpaw) allodynia, in part, through attenuation of CGRP expression in lumbar DRG sensory neurons. NGF decreases rat exploratory behavior and increases spontaneous pain for which passive SM acts to mitigate these pain-related behavioral changes. These initial study findings suggest that beginning daily SM soon after injury onset might act to minimize or prevent the development of LBP by reducing production of pain-related neuropeptides.

Walking Speed Reliably Measures Clinically Significant Changes in Gait by Directional Deep Brain Stimulation.

Introduction: Although deep brain stimulation (DBS) often improves levodopa-responsive gait symptoms, robust therapies for gait dysfunction from Parkinson's disease (PD) remain a major unmet need. Walking speed could represent a simple, integrated tool to assess DBS efficacy but is often not examined systematically or quantitatively during DBS programming. Here we investigate the reliability and functional significance of changes in gait by directional DBS in the subthalamic nucleus. Methods: Nineteen patients underwent unilateral subthalamic nucleus DBS surgery with an eight-contact directional lead (1-3-3-1 configuration) in the most severely affected hemisphere. They arrived off dopaminergic medications >12 h preoperatively and for device activation 1 month after surgery. We measured a comfortable walking speed using an instrumented walkway with DBS off and at each of 10 stimulation configurations (six directional contacts, two virtual rings, and two circular rings) at the midpoint of the therapeutic window. Repeated measures of ANOVA contrasted preoperative vs. maximum and minimum walking speeds across DBS configurations during device activation. Intraclass correlation coefficients examined walking speed reliability across the four trials within each DBS configuration. We also investigated whether changes in walking speed related to modification of step length vs. cadence with a one-sample t-test. Results: Mean comfortable walking speed improved significantly with DBS on vs. both DBS off and minimum speeds with DBS on (p < 0.001, respectively). Pairwise comparisons showed no significant difference between DBS off and minimum comfortable walking speed with DBS on (p = 1.000). Intraclass correlations were ≥0.949 within each condition. Changes in comfortable walk speed were conferred primarily by changes in step length (p < 0.004). Conclusion: Acute assessment of walking speed is a reliable, clinically meaningful measure of gait function during DBS activation. Directional and circular unilateral subthalamic DBS in appropriate configurations elicit acute and clinically significant improvements in gait dysfunction related to PD. Next-generation directional DBS technologies have significant potential to enhance gait by individually tailoring stimulation parameters to optimize efficacy.