Tissue loading and microstructure regulate the deformation of embedded nerve fibres: predictions from single-scale and multiscale simulations

Abstract

Excessive deformation of nerve fibres (axons) in the spinal facet capsular ligaments (FCLs) can be a cause of pain. The axons are embedded in the fibrous extracellular matrix (ECM) of FCLs, so understanding how local fibre organization and micromechanics modulate their mechanical behaviour is essential. We constructed a computational discrete-fibre model of an axon embedded in a collagen fibre network attached to the axon by distinct fibre-axon connections. This model was used to relate the axonal deformation to the fibre alignment and collagen volume concentration of the surrounding network during transverse, axial and shear deformations. Our results showed that fibre alignment affects axonal deformation only during transverse and axial loading, but higher collagen volume concentration results in larger overall axonal strains for all loading cases. Furthermore, axial loading leads to the largest stretch of axonal microtubules and induces the largest forces on axon's surface in most cases. Comparison between this model and a multiscale continuum model for a representative case showed that although both models predicted similar averaged axonal strains, strain was more heterogeneous in the discrete-fibre model.

Intra-articular collagenase in the spinal facet joint induces pain, DRG neuron dysregulation and increased MMP-1 absent evidence of joint destruction

“…Although it is well-established that nociceptive signaling is activated in afferents by stretch-induced changes to their local matrix 7,11,67 , this study suggests that degradation-induced changes alone, absent any stretch, may also affect neuronal signaling. This notion is supported by the maintained neuronal signaling (Fig.…”

“…Mechanosensitive afferent fibers and FLS cells embedded in the collagenous ligament respond to changes in their mechanical microenvironment via adhesive interactions with the ECM 7 ; such disruption of collagen types involved in ECM cohesion may directly induce several behavioral characteristics of pain 66 . Moreover, mechanically-triggered neuronal 67 and fibroblast 46 responses depend on collagen concentration , so a collagenase-induced decrease in collagen (Fig. 6 a) could alter how cells respond to mechanical cues after exposure.…”

The role of the facet capsular ligament in providing spinal stability

“…For the FCL to serve a proprioceptive role, which has been suggested by previous works [21, 22], there must be sufficiently large strains in the tissue to trigger a neuronal response. In this work, we found large stretches for loading levels in all types of bending, which may play an important physiological role - as it is known the FCL contains proprioceptive nerves [8].…”

“…Because the FCL is highly innervated, it is important to understand the local alterations, including the FCL stretch and relative facet surface motion. This could be an important mechanism of LBP, whereas the loss of FCL mechanical competency leads to an increased stretch and nerve response, resulting in pain [21, 22]. Previous studies have investigated the effect of the removal of ligaments on spine motion [18, 23], but none investigated the effect of motion on the FCL strains or the facet joint space.…”

Multiscale modelling of the human lumbar facet capsular ligament: analysing spinal motion from the joint to the neurons

“…We first constructed a structure-based multiscale finiteelement (FE) model based on the measured fibre structure, and we then used this model to obtain the FCL's strains during physiological motions. A supervised machine learning approach, trained based on our previous axon-fibre model [6], was used next to estimate the mechanical response of the underlying axons during spinal motions. Figure 1 shows an overview of our methodology to estimate the mechanical response of the axon during spinal motions.…”