Disruption of axoplasmic transport induces mechanical sensitivity in intact rat C‐fibre nociceptor axons

Abstract

Peripheral nerve inflammation can cause axons conducting through the inflamed site to become mechanically sensitive. Axonal mechanical sensitivity (AMS) of intact axons may explain symptoms in a diverse number of conditions characterized by radiating pain evoked by movements of the affected nerve. Because nerve inflammation also disrupts axoplasmic transport, we hypothesized that the disruption of axoplasmic transport by nerve inflammation could cause the cellular components responsible for mechanical transduction to accumulate and become inserted at the inflamed site, causing AMS. This was tested by examining AMS in C-fibre nociceptors following the application of axoplasmic transport blockers (colchicine and vinblastine) to the sciatic nerve. Both 10 mM colchicine and 0.1 mM vinblastine caused AMS to develop in 30.6% and 33.3% of intact axons, respectively (P < 0.05 compared to sham treatment). Since high doses of colchicine (> 50 mM) can damage axons, and inflammation is involved in the removal of axonal debris, experiments were performed to assess conduction across the treatment site as well as signs of inflammation. Results indicated minimal axonal loss (95% of A-and C-fibres conducting), consistent with the normal microscopic appearance of the colchicine treatment site and absence of ED1-positive (recruited) macrophages. In a separate series of experiments, the block of axoplasmic transport proximal to a localized neuritis significantly reduced inflammation-induced AMS (15.6% compared to 55.6%; P < 0.05), further supporting that the components necessary for AMS are moved by anterograde transport. In summary, nerve inflammation that causes the disruption of axoplasmic transport in patients with painful conditions may result in the accumulation and insertion of mechanosensitive elements at the inflamed site.

Sensory Transduction in Peripheral Nerve Axons Elicits Ectopic Action Potentials

“…This proportion is comparable with the number of mechanically sensitive C-fiber axons found by Dilley and Bove (2008) (3 of 43), who demonstrated that blocking axoplasmic transport increases the prevalence of axonal mechanosensitivity proximal of the block (to 11 of 36). The von Frey threshold of the individual axon was always much higher than that of the RF.…”

The effects of neurodynamic mobilization on fluid dispersion within the tibial nerve at the ankle: an unembalmed cadaveric study

“…15,23 Maintaining healthy nerve function using neurodynamic techniques may occur by promoting uninterrupted axonal transport, thereby preventing deposition of mechanosensitivity elements, the presence of which results in pain and limited neural movement. 8,22 In the early stages of stretch injury or compression, the ability to prevent or at least reduce edema may prevent or slow the inhibition of blood flow, 15,23 thus preventing the sequelae leading to impaired axonal transport, 18,20 demyelination, 11,24 loss of elasticity due to fibrosis or adhesions, 46,63 and ultimately to alteration in nerve structure and function. 19,24,27 The ability to promote fluid dispersion using range of motion may provide a means to break the cycle of edema formation leading to fibrosis, 50 which may in turn lead again to edema formation.…”

“…These disorders include compression syndromes or other neuromuscular conditions that may be accompanied by neuropathic pain. [1][2][3][4][5] Damaged nerves exhibit predictable pathophysiological responses including impaired nerve mobility, [6][7][8][9] increased mechanosensitivity, 8,10 impaired nerve conduction, [11][12][13] nerve tissue ischemia, 14,15 axonal transport inhibition, [16][17][18][19][20][21][22] and intraneural edema. 15,[23][24][25][26][27][28] Impaired nerve mobility and increased mechanosensitivity provide the basis for existing studies of neurodynamic techniques.…”

Effects of lower limb neurodynamic mobilization on intraneural fluid dispersion of the fourth lumbar nerve root: an unembalmed cadaveric investigation

“…3,35 Neurodynamic techniques may promote healthy nerve function by promoting reduced oedema and changing intraneural pressure, which lead to improvement in axonal transport and prevention of the deposit of mechanosensitivity factors that result in pain and limitations in neural movement. 46,47 During the initial stages of neural tension or compression injury, the prevention or reduction of oedema may limit compromise of blood flow. The promotion of intraneural fluid dispersion through the incorporation of lower limb movement may provide a mechanism to disrupt the cycle of oedema formation and the subsequent consequences that contribute to fibrosis.…”