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 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.

scholarly journals Enhanced T-type calcium channel 3.2 activity in sensory neurons contributes to neuropathic-like pain of monosodium iodoacetate-induced knee osteoarthritis

2020 ◽  
Vol 16 ◽  
pp. 174480692096380
Author(s):  
Seung Min Shin ◽  
Yongsong Cai ◽  
Brandon Itson-Zoske ◽  
Chensheng Qiu ◽  
Xu Hao ◽  
...  
Keyword(s):  
Sensory Neuron ◽  
Sensory Neurons ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Spinal Dorsal Horn ◽  
Primary Sensory Neurons ◽  
Primary Sensory Neuron ◽  
Spinal Dorsal ◽  
Osteoarthritis Pain ◽  
Monosodium Iodoacetate

The monosodium iodoacetate knee osteoarthritis model has been widely used for the evaluation of osteoarthritis pain, but the pathogenesis of associated chronic pain is not fully understood. The T-type calcium channel 3.2 (CaV3.2) is abundantly expressed in the primary sensory neurons, in which it regulates neuronal excitability at both the somata and peripheral terminals and facilitates spontaneous neurotransmitter release at the spinal terminals. In this study, we investigated the involvement of primary sensory neuron-CaV3.2 activation in monosodium iodoacetate osteoarthritis pain. Knee joint osteoarthritis pain was induced by intra-articular injection of monosodium iodoacetate (2 mg) in rats, and sensory behavior was evaluated for 35 days. At that time, knee joint structural histology, primary sensory neuron injury, and inflammatory gliosis in lumbar dorsal root ganglia, and spinal dorsal horn were examined. Primary sensory neuron-T-type calcium channel current by patch-clamp recording and CaV3.2 expression by immunohistochemistry and immunoblots were determined. In a subset of animals, pain relief by CaV3.2 inhibition after delivery of CaV3.2 inhibitor TTA-P2 into sciatic nerve was investigated. Knee injection of monosodium iodoacetate resulted in osteoarthritis histopathology, weight-bearing asymmetry, sensory hypersensitivity of the ipsilateral hindpaw, and inflammatory gliosis in the ipsilateral dorsal root ganglia, sciatic nerve, and spinal dorsal horn. Neuronal injury marker ATF-3 was extensively upregulated in primary sensory neurons, suggesting that neuronal damage was beyond merely knee-innervating primary sensory neurons. T-type current in dissociated primary sensory neurons from lumbar dorsal root ganglia of monosodium iodoacetate rats was significantly increased, and CaV3.2 protein levels in the dorsal root ganglia and spinal dorsal horn ipsilateral to monosodium iodoacetate by immunoblots were significantly increased, compared to controls. Perineural application of TTA-P2 into the ipsilateral sciatic nerve alleviated mechanical hypersensitivity and weight-bearing asymmetry in monosodium iodoacetate osteoarthritis rats. Overall, our findings demonstrate an elevated CaV3.2 expression and enhanced function of primary sensory neuron-T channels in the monosodium iodoacetate osteoarthritis pain. Further study is needed to delineate the importance of dysfunctional primary sensory neuron-CaV3.2 in osteoarthritis pain.

scholarly journals G9a inhibits CREB-triggered expression of mu opioid receptor in primary sensory neurons following peripheral nerve injury

2016 ◽  
Vol 12 ◽  
pp. 174480691668224 ◽  
Author(s):  
Lingli Liang ◽  
Jian-Yuan Zhao ◽  
Xiyao Gu ◽  
Shaogen Wu ◽  
Kai Mo ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Opioid Receptor ◽  
Sensory Neurons ◽  
Peripheral Nerve Injury ◽  
Mu Opioid Receptor ◽  
Primary Sensory Neurons ◽  
Mu Opioid
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