The Prediction of Nociceptive Neural Activity in Passive Tissues following Lumbar Spine Flexion
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Low back pain is a costly and debilitating disorder; however, most cases are categorized as being non-specific: low back pain without an identifiable origin or cause. Non-specific low back pain can be broadly considered and treated as either musculoskeletal disorders or pain disorders. In the musculoskeletal case, mechanics and loading history are believed to disrupt or damage tissues in the low back, which then generate nociceptive signals to be interpreted as pain. If the low back pain is a pain disorder, the disruption or damage is not with the tissues of the lower back, but rather the nervous system that transmits or interprets these nociceptive signals. Additionally, these subcategories of non-specific low back pain are not wholly independent since mechanical exposures can influence nervous system activity and vice versa. A specific outcome of this interconnectedness between mechanics and neural encoding is that a mechanical exposure can alter our ability to detect mechanical loads or mechanical sensitivity. One mechanical exposure that is linked to low back pain development and has been documented to alter neural activity is lumbar spine flexion. The purpose of this thesis was to determine the extent and mechanisms underlying how lumbar spine flexion can alter lower back mechanical sensitivity through a combination of viscoelastic creep and muscle activity, and to determine the implications those changes could have on the development of low back pain. The methods undertaken to achieve this thesis’ purpose were a combination of in-vivo human laboratory experiments, ex-vivo benchtop histology and mechanical testing, and in-silico modelling across four studies. Studies 1 and 2 quantified how mechanical sensitivity was altered over time in response to static and repetitive lumbar spine flexion respectively, Study 3 quantified the innervation properties of lumbar spine tissues, and Study 4 simulated mechanical exposures before and after lumbar spine flexion exposures to determine the nociceptive neural activity those exposures and conditions could generate. The first two studies employed a similar design and methodology measuring mechanical sensitivity and biomechanical variables before and up to 40 minutes after a 10-minute lumbar spine flexion exposure. For Study 1, the exposure was a static, seated, maximal lumbar spine flexion exposure and for Study 2, the exposure was a repetitive, standing, maximal lumbar spine flexion exposure. A custom motorized pressure algometer was constructed for these studies and used to track three measures of mechanical sensitivity—pressure-pain threshold, stimulus intensity, and stimulus unpleasantness—in the lower back and tibial shaft. Accelerometry was used in both studies to track the development and recovery from viscoelastic creep through lumbar spine flexion range of motion, and surface electromyography was used to determine flexion-relaxation (mean amplitude) in Study 1, and muscle fatigue (mean power frequency) in Study 2. Isometric joint strength and ratings of perceived exertion were also measured in Study 2. These data were fed into two main statistical processes: the first aimed to determine the time-course of mechanical sensitivity changes in the lower back relative to the tibial control site, and the second was to determine if any of the biomechanical variables (creep, muscle use, strength) or tibial mechanical sensitivities could predict lower back mechanical sensitivity changes. The static exposure generated a 10.3% creep response (4.4 ± 2.7°) in flexion range of motion that lasted for at least 40 minutes after the exposure. This exposure caused a transient increase in lower back stimulus unpleasantness but otherwise did not affect mechanical sensitivity nor did it affect flexion-relaxation. The strongest predictor of lower back mechanical sensitivity throughout the static exposure was the tibial surrogate; however, the magnitude of creep was also a significant predictor of changes in lower back pressure-pain thresholds. Despite being significant, these significant predictors could not explain the majority to the variance in mechanical sensitivity, and these changes appear more related to emotional affect than a physiological response. Study 1 concluded that a static lumbar spine flexion exposure that did not incorporate muscle activity did not alter nociceptive activity but could shape how nociceptive activity is experienced. The repetitive exposure generated a 5.0% creep response (2.7 ± 1.4°) in flexion range of motion dissipated within 5 minutes of the exposure ending. This exposure caused an immediate and transient decrease in lumbar spine extensor mean power frequency (5.1%) and lower back joint strength (9.8%) indicative of muscle fatigue, and a delayed 13.6% increase in lower back pressure-pain thresholds occurring 10 minutes after the exposure ended. Like Study 1, tibial mechanical sensitivities were the strongest predictor of lower back mechanical sensitivities, however interaction terms between these tibial surrogates and either creep magnitude or fatigue indicators (mean power frequency and strength) were also significant predictors. The delayed desensitization following this repetitive exposure was believed to arise from a combination of creep development and muscle use. The third study used lumbar spine tissues harvested from four cadaveric donors to determine the relative concentration of four neural membrane molecules (Protein Gene Product 9.5 (PGP9.5), Calcitonin Gene-Related Peptide, Bradykinin B1-Receptor, and Acid-Sensing Ion Channel 3 (ASIC3)) relevant to detecting mechanical stimuli in three tissues (dermal skin, superficial posterior annulus fibrosus, and the supraspinous-interspinous ligament complex) using Western Blotting. Only PGP9.5 and ASIC3 were found consistently in any of the three tissues. PGP9.5 had similar concentrations in skin and ligament, both of which were at least 12.8 times higher than in annular tissues. ASIC3 was most common in skin, followed by ligament, then annulus fibrosus, however the ratio of ASIC3:PGP9.5 was highest in annular tissue. The fourth study documents a model of nociceptive activity that predicts the likelihood that three exposures (pressure-pain threshold, flexion range of motion, and tissue failure) would generate nociceptive activity in the brainstem given a tissue (skin, annulus, or ligament), a viscoelastic state, ζ(t), and a muscle activity state, ϕ(t). The model simulated a single tissue-exposure combination for a sample of 100 mechanical sensitivities derived from the data in Studies 1 and 2. The model itself consisted of a Sensitivity Module that converted a tissue stress to an electrical current and a Neurological Module that used the electrical current to simulate the behaviour of a network of Hodgkin-Huxley neurons. The pressure-pain threshold exposure was used to validate the model and derive values for ζ(t) and ϕ(t), which were then applied to the other two exposures in annular and ligament tissues. While ζ(t), representing any effects related to creep following lumbar spine flexion, had minimal effects on nociceptive neural activity, ϕ(t), representing muscle activity-related effects of lumbar spine flexion, could inhibit nociceptive activity substantially. A major prediction from the model is that annulus fibrosus failure would be unlikely to generate any nociceptive activity in 12% of the population, and that characteristics of the exposure could increase that percentage to as many as 99.9% depending on the mode of failure. Flexion range of motion consistently generated no nociceptive activity in all tissues and conditions, and ligament failure consistently generated nociceptive activity regardless of other factors. While both viscoelastic creep and muscle activity related to lumbar spine flexion can influence mechanical sensitivity, the effects of muscle activity were more prominent, and could meaningfully influence the connection between tissue disruption and low back pain. These effects were most notable in exposures that have the potential to damage the annulus fibrosus.
Cite this version of the work
Daniel Viggiani (2021). The Prediction of Nociceptive Neural Activity in Passive Tissues following Lumbar Spine Flexion. UWSpace. http://hdl.handle.net/10012/17727