Inflammation Induces Ectopic Mechanical Sensitivity in Axons of Nociceptors Innervating Deep Tissues

Abstract

A variety of seemingly diverse pain syndromes are characterized by movement-induced pain radiating in the distribution of a peripheral nerve or nerve root. This could be explained by the induction of ectopic mechanical sensitivity in intact sensory axons. Here we show that inflammation led to mechanical sensitivity of the axons of a subset of mechanically sensitive primary sensory neurons. Dorsal root recordings were made from 194 mechanically sensitive neurons that innervated deep and cutaneous structures and had C, Adelta, and Aalphabeta conduction velocities. No axons of any category were mechanically sensitive in control experiments. However, the axons of neurons innervating deep structures and having C- or Adelta-conduction velocities became mechanically sensitive during the neuritis, and also exhibited an increased incidence of spontaneous discharge. The incidence of mechanical sensitivity followed a distinct time course. In some cases, paw withdrawal thresholds were obtained after neuritis induction. The time course of the resultant hypersensitivity was not directly related to the time course of the axonal mechanical sensitivity. Ectopic axonal mechanical sensitivity could explain some types of radiating, nerve-related pain coexisting with diseases of seemingly diverse etiologies.

Memory-Like Alterations inAplysiaAxons after Nerve Injury or Localized Depolarization

“…Under normal conditions, axons have not been reported to exhibit long-term, adaptive increases in excitability. However, mammalian sensory axons can display persistent hyperexcitability at sites of nerve injury (Zimmermann, 2001) and inflammation (Tal and Eliav, 1996;Eliav et al, 2001;Bove et al, 2003).…”

Ulnar Nerve Neurodynamic Test: Study of the Normal Sensory Response in Asymptomatic Individuals

“…7,8,16,19,22,35 Neurodynamic tests are considered to be able to detect increased nerve mechanosensitivity. 12,15,16,19,22,33 This heightened sensitivity in response to mechanical stimuli has been attributed to local inflammatory processes within the nerve 1,4,10,11,14,22 that are specifically related to its connective tissue. 32 When determining whether the result of a neurodynamic test is suggestive of increased nerve mechanosensitivity and therefore relevant to current patient complaints, it is important to consider several factors.…”

Different Nerve-Gliding Exercises Induce Different Magnitudes of Median Nerve Longitudinal Excursion: An In Vivo Study Using Dynamic Ultrasound Imaging

“…22 Animal experiments have demonstrated that local nerve inflammation results in increased mechanical sensitivity of otherwise intact axons. 1 When a nerve is inflamed, minimal elongation ( 3%) or locally applied pressure can trigger ectopic impulse generation, 14 which may lead to the provocation of pain and other symptoms. Although these recent insights in pathophysiology Controlled laboratory study using single-group, within-subject comparisons.…”