scholarly journals Time course of ongoing activity during neuritis and following axonal transport disruption

2018 ◽  
Vol 119 (5) ◽  
pp. 1993-2000 ◽  
Author(s):  
Ieva Satkeviciute ◽  
George Goodwin ◽  
Geoffrey M. Bove ◽  
Andrew Dilley
Keyword(s):  
Axonal Transport ◽  
Sensory Neurons ◽  
Time Course ◽  
Primary Sensory Neurons ◽  
Mechanical Sensitivity ◽  
Ongoing Activity ◽  
Associated Symptoms ◽  
C Fiber ◽  
Cutaneous Hypersensitivity ◽  
Time Point

Local nerve inflammation (neuritis) leads to ongoing activity and axonal mechanical sensitivity (AMS) along intact nociceptor axons and disrupts axonal transport. This phenomenon forms the most feasible cause of radiating pain, such as sciatica. We have previously shown that axonal transport disruption without inflammation or degeneration also leads to AMS but does not cause ongoing activity at the time point when AMS occurs, despite causing cutaneous hypersensitivity. However, there have been no systematic studies of ongoing activity during neuritis or noninflammatory axonal transport disruption. In this study, we present the time course of ongoing activity from primary sensory neurons following neuritis and vinblastine-induced axonal transport disruption. Whereas 24% of C/slow Aδ-fiber neurons had ongoing activity during neuritis, few (<10%) A- and C-fiber neurons showed ongoing activity 1–15 days following vinblastine treatment. In contrast, AMS increased transiently at the vinblastine treatment site, peaking on days 4–5 (28% of C/slow Aδ-fiber neurons) and resolved by day 15. Conduction velocities were slowed in all groups. In summary, the disruption of axonal transport without inflammation does not lead to ongoing activity in sensory neurons, including nociceptors, but does cause a rapid and transient development of AMS. Because it is proposed that AMS underlies mechanically induced radiating pain, and a transient disruption of axonal transport (as previously reported) leads to transient AMS, it follows that processes that disrupt axonal transport, such as neuritis, must persist to maintain AMS and the associated symptoms. NEW & NOTEWORTHY Many patients with radiating pain lack signs of nerve injury on clinical examination but may have neuritis, which disrupts axonal transport. We have shown that axonal transport disruption does not induce ongoing activity in primary sensory neurons but does cause transient axonal mechanical sensitivity. The present data complete a profile of key axonal sensitivities following axonal transport disruption. Collectively, this profile supports that an active peripheral process is necessary for maintained axonal sensitivities.

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

2003 ◽  
Vol 90 (3) ◽  
pp. 1949-1955 ◽  
Author(s):  
Geoffrey M. Bove ◽  
Bernard J. Ransil ◽  
Hsi-Chiang Lin ◽  
Jeong-Gill Leem
Keyword(s):  
Peripheral Nerve ◽  
Sensory Neurons ◽  
Dorsal Root ◽  
Time Course ◽  
Spontaneous Discharge ◽  
Primary Sensory Neurons ◽  
Mechanical Sensitivity ◽  
Pain Syndromes ◽  
Sensory Axons ◽  
Conduction Velocities

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, Aδ, and Aαβ 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 Aδ-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.

scholarly journals Cutaneous neurturin overexpression alters mechanical, thermal, and cold responsiveness in physiologically identified primary afferents

2017 ◽  
Vol 117 (3) ◽  
pp. 1258-1265 ◽  
Author(s):  
Michael P. Jankowski ◽  
Kyle M. Baumbauer ◽  
Ting Wang ◽  
Kathryn M. Albers ◽  
Brian M. Davis ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Neurotrophic Factors ◽  
Ex Vivo ◽  
Second Phase ◽  
Primary Sensory Neurons ◽  
Mechanical Stimuli ◽  
Wild Type Littermate ◽  
Basal Keratinocytes ◽  
C Fiber ◽  
The Impact

Neurotrophic factors play an important role in the regulation of functional properties of sensory neurons under normal and pathological conditions. The GDNF family member neurturin is one such factor that has been linked to modulating responsiveness to peripheral stimuli. Neurturin binds to the GFRα2 receptor, a receptor found primarily in isolectin B4-expressing polymodal cutaneous nociceptors. Previous work has shown that knockout of GFRα2 alters heat, but not mechanical, responses in dissociated sensory neurons and reduces pain-related behaviors during the second phase of the formalin test. Research has also shown that overexpression of neurturin in basal keratinocytes increases behavioral responsiveness to mechanical stimulation and innocuous cooling of the skin without affecting noxious heat responses. Here we directly examined the impact of neurturin overexpression on cutaneous afferent function. We compared physiological responses of individual sensory neurons to mechanical and thermal stimulation of the skin, using an ex vivo skin-nerve-dorsal root ganglion-spinal cord preparation produced from neurturin-overexpressing (NRTN/OE) mice and wild-type littermate controls. We found that neurturin overexpression increases responsiveness to innocuous mechanical stimuli in A-fiber nociceptors, alters thermal responses in the polymodal subpopulation of C-fiber sensory neurons, and changes the relative numbers of mechanically sensitive but thermally insensitive C-fiber afferents. These results demonstrate the potential roles of different functional groups of sensory neurons in the behavioral changes observed in mice overexpressing cutaneous neurturin and highlight the importance of neurturin in regulating cutaneous afferent response properties. NEW & NOTEWORTHY GDNF family neurotrophic factors regulate the development and function of primary sensory neurons. Of these, neurturin has been shown to modulate mechanical and cooling sensitivity behaviorally. Here we show that overexpression of neurturin in basal keratinocytes regulates mechanical responsiveness in A-fiber primary sensory neurons while increasing the overall numbers of cold-sensing units. Results demonstrate a crucial role for cutaneous neurturin in modulating responsiveness to peripheral stimuli at the level of the primary afferent.

scholarly journals Endosome-mediated retrograde axonal transport of P2X3 receptor signals in primary sensory neurons

Cell Research ◽  
2011 ◽  
Vol 22 (4) ◽  
pp. 677-696 ◽  
Author(s):  
Xu-Qiao Chen ◽  
Bin Wang ◽  
Chengbiao Wu ◽  
Jin Pan ◽  
Bo Yuan ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Sensory Neurons ◽  
Retrograde Axonal Transport ◽  
Primary Sensory Neurons ◽  
P2x3 Receptor

Axonal transport of BDNF precursor in primary sensory neurons

2006 ◽  
Vol 24 (9) ◽  
pp. 2444-2452 ◽  
Author(s):  
Hui Wang ◽  
Linda Lin-yan Wu ◽  
Xing-Yun Song ◽  
Xue-Gang Luo ◽  
Jin-Hua Zhong ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Sensory Neurons ◽  
Primary Sensory Neurons
Sign in / Sign up

Export Citation Format

Share Document