Sensory neurons that are mechanically sensitive innervate all of the paraspinal connective tissues including ligament, joint capsule, annulus fibrosus of the IVD, muscle, tendon, and skin. These afferents can be broadly classified into two subcategories based on whether they respond to non-noxious or noxious mechanical loads (mechanoreceptors or mechanonociceptors, respectively). By definition, a noxious mechanical load is such that it actually is or is close to damaging the tissue. Histologically, mechanonociceptors (MN) have small diameter axons (< ~ 1mm) with either no or minimal myelination (and hence conduct action potentials at < ~2 m/s) and their receptive endings are either “free” or non-corpuscle. In contrast, mechanoreceptors (MR) have larger diameter axons with myelination (conducting at > 20 m/s) and terminal endings with distinct corpusculature. During an externally applied mechanical load (e.g., compression and/or stretch), the terminal endings experience the internal locally developed stress (related to force) and/or strain (related to deformation). Using intact, ex-vivo nerve-tissue preparations, at the macroscopic level both MR and MN have been shown to encode the local stress—or a stress-related quantity, rather than the strain, deformation, or force. At the cellular level, the stress-field in the extracellular matrix (collagen, elastin, laminin, etc.) is coupled to the cytoskeleton by transmembrane proteins called integrins. Disrupting the integrin attachment with monoclonal antibodies or specific RGD peptides substantial reduces MR sensitivity to mechanical stimuli and MN inflammatory-induced hyperalgesia.
Recommendations for future research: 1) Determine local and systemic inter-relationships between microvasculature and MN peripheral sensitization. 2) Determine effects of peripheral mechanical stimuli (e.g., spinal manipulation) on spinal cord gating mechanisms and synaptic plasticity.