The Anatomical RecordContinues Its Fascination with the Bridges of the Nervous System in Our Thematic Papers Issue on Peripheral Nerve Injury and Repair

We investigated the changes induced in crossed extensor reflex responses after peripheral nerve injury and repair in the rat. Adults rats were submitted to non repaired sciatic nerve crush (CRH, n = 9), section repaired by either aligned epineurial suture (CS, n = 11) or silicone tube (SIL4, n = 13), and 8 mm resection repaired by tubulization (SIL8, n = 12). To assess reinnervation, the sciatic nerve was stimulated proximal to the injury site, and the evoked compound muscle action potential (M and H waves) from tibialis anterior and plantar muscles and nerve action potential (CNAP) from the tibial nerve and the 4th digital nerve were recorded at monthly intervals for 3 mo postoperation. Nociceptive reinnervation to the hindpaw was also assessed by plantar algesimetry. Crossed extensor reflexes were evoked by stimulation of the tibial nerve at the ankle and recorded from the contralateral tibialis anterior muscle. Reinnervation of the hindpaw increased progressively with time during the 3 mo after lesion. The degree of muscle and sensory target reinnervation was dependent on the severity of the injury and the nerve gap created. The crossed extensor reflex consisted of three bursts of activity (C1, C2, and C3) of gradually longer latency, lower amplitude, and higher threshold in control rats. During follow-up after sciatic nerve injury, all animals in the operated groups showed recovery of components C1 and C2 and of the reflex H wave, whereas component C3 was detected in a significantly lower proportion of animals in groups with tube repair. The maximal amplitude of components C1 and C2 recovered to values higher than preoperative values, reaching final levels between 150 and 245% at the end of the follow-up in groups CRH, CS, and SIL4. When reflex amplitude was normalized by the CNAP amplitude of the regenerated tibial nerve, components C1 (300–400%) and C2 (150–350%) showed highly increased responses, while C3 was similar to baseline levels. In conclusion, reflexes mediated by myelinated sensory afferents showed, after nerve injuries, a higher degree of facilitation than those mediated by unmyelinated fibers. These changes tended to decline toward baseline values with progressive reinnervation but still remained significant 3 mo after injury.

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Role of the immune system in neuropathic pain

Scandinavian Journal of Pain ◽

10.1515/sjpain-2019-0138 ◽

2019 ◽

Vol 20 (1) ◽

pp. 33-37 ◽

Cited By ~ 16

Author(s):

Marzia Malcangio

Keyword(s):

Spinal Cord ◽

Chronic Pain ◽

Nervous System ◽

Neuropathic Pain ◽

Immune System ◽

Peripheral Nerve ◽

Dorsal Horn ◽

Nerve Injury ◽

Immune Cells ◽

Peripheral Nerve Injury

AbstractBackgroundAcute pain is a warning mechanism that exists to prevent tissue damage, however pain can outlast its protective purpose and persist beyond injury, becoming chronic. Chronic Pain is maladaptive and needs addressing as available medicines are only partially effective and cause severe side effects. There are profound differences between acute and chronic pain. Dramatic changes occur in both peripheral and central pathways resulting in the pain system being sensitised, thereby leading to exaggerated responses to noxious stimuli (hyperalgesia) and responses to non-noxious stimuli (allodynia).Critical role for immune system cells in chronic painPreclinical models of neuropathic pain provide evidence for a critical mechanistic role for immune cells in the chronicity of pain. Importantly, human imaging studies are consistent with preclinical findings, with glial activation evident in the brain of patients experiencing chronic pain. Indeed, immune cells are no longer considered to be passive bystanders in the nervous system; a consensus is emerging that, through their communication with neurons, they can both propagate and maintain disease states, including neuropathic pain. The focus of this review is on the plastic changes that occur under neuropathic pain conditions at the site of nerve injury, the dorsal root ganglia (DRG) and the dorsal horn of the spinal cord. At these sites both endothelial damage and increased neuronal activity result in recruitment of monocytes/macrophages (peripherally) and activation of microglia (centrally), which release mediators that lead to sensitisation of neurons thereby enabling positive feedback that sustains chronic pain.Immune system reactions to peripheral nerve injuriesAt the site of peripheral nerve injury following chemotherapy treatment for cancer for example, the occurrence of endothelial activation results in recruitment of CX3C chemokine receptor 1 (CX3CR1)-expressing monocytes/macrophages, which sensitise nociceptive neurons through the release of reactive oxygen species (ROS) that activate transient receptor potential ankyrin 1 (TRPA1) channels to evoke a pain response. In the DRG, neuro-immune cross talk following peripheral nerve injury is accomplished through the release of extracellular vesicles by neurons, which are engulfed by nearby macrophages. These vesicles deliver several determinants including microRNAs (miRs), with the potential to afford long-term alterations in macrophages that impact pain mechanisms. On one hand the delivery of neuron-derived miR-21 to macrophages for example, polarises these cells towards a pro-inflammatory/pro-nociceptive phenotype; on the other hand, silencing miR-21 expression in sensory neurons prevents both development of neuropathic allodynia and recruitment of macrophages in the DRG.Immune system mechanisms in the central nervous systemIn the dorsal horn of the spinal cord, growing evidence over the last two decades has delineated signalling pathways that mediate neuron-microglia communication such as P2X4/BDNF/GABAA, P2X7/Cathepsin S/Fractalkine/CX3CR1, and CSF-1/CSF-1R/DAP12 pathway-dependent mechanisms.Conclusions and implicationsDefinition of the modalities by which neuron and immune cells communicate at different locations of the pain pathway under neuropathic pain states constitutes innovative biology that takes the pain field in a different direction and provides opportunities for novel approaches for the treatment of chronic pain.

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A comparison of two-dimensional and three-dimensional techniques for determining the kinematic patterns for hindlimb obstacle clearance during sheep locomotion.

10.21203/rs.3.rs-27991/v1 ◽

2020 ◽

Author(s):

Camila Cardoso Diogo ◽

Bárbara Fonseca ◽

Francisca S.M. Almeida ◽

Luís Maltez da Costa ◽

José Eduardo Pereira ◽

...

Keyword(s):

Peripheral Nerve ◽

Nerve Injury ◽

Peripheral Nerve Injury ◽

Time Course ◽

Objective Assessment ◽

Three Dimensional ◽

Two Dimensional ◽

Ovine Model ◽

Obstacle Clearance ◽

Injury And Repair

Abstract Background: Analysis of locomotion is often used as a measure for impairment and recovery following experimental peripheral nerve injury. Compared to rodents, sheep offer several attractive features as an experimental model for studying peripheral nerve regeneration. There are no studies on locomotion outcomes after peripheral nerve injury and repair in the sheep model. In the present study, we performed and compared two-dimensional (2D) and, for the first time, three-dimensional (3D) hindlimb kinematics during obstacle avoidance in the ovine model. This study aimed to obtain kinematic data to serve as a template for an objective assessment of the ankle joint motion in future studies of common peroneal nerve (CP) injury and repair in the ovine model. Results: The strategy used by the sheep to bring the hindlimb over a moderately high obstacle, set to 10% of its hindlimb length, was the pronounced knee, ankle and metatarsophalangeal flexion when approaching and clearing the obstacle. Despite the overall time course kinematic patterns about the hip, knee, ankle, and metatarsophalangeal were identical, we found significant differences between values of the 2D and 3D joint angular motion. Conclusions: Our results show that the most apparent changes that occurred during the gait cycle were for the ankle and metatarsophalangeal joints, whereas the hip and knee joints were much less affected. Data and techniques described here are likely to be useful for an objective assessment of altered gait after CP injury and repair in an ovine model.

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High-resolution live imaging reveals axon-glia interactions during peripheral nerve injury and repair in zebrafish

Disease Models & Mechanisms ◽

10.1242/dmm.018184 ◽

2015 ◽

Vol 8 (6) ◽

pp. 553-564 ◽

Cited By ~ 24

Author(s):

Y. Xiao ◽

A. Faucherre ◽

L. Pola-Morell ◽

J. M. Heddleston ◽

T.-L. Liu ◽

...

Keyword(s):

High Resolution ◽

Peripheral Nerve ◽

Nerve Injury ◽

Peripheral Nerve Injury ◽

Live Imaging ◽

Injury And Repair

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Trigeminal ganglion response to immediate and delayed peripheral nerve injury and repair

Journal of Oral and Maxillofacial Surgery ◽

10.1016/0278-2391(89)90621-6 ◽

1989 ◽

Vol 47 (8) ◽

pp. 102-103 ◽

Cited By ~ 2

Author(s):

John R. Zuniga

Keyword(s):

Peripheral Nerve ◽

Nerve Injury ◽

Trigeminal Ganglion ◽

Peripheral Nerve Injury ◽

Injury And Repair

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Assessment of Sensibility after Nerve Injury and Repair: A Systematic Review of Evidence for Validity, Reliability and Responsiveness of Tests

Journal of Hand Surgery (European Volume) ◽

10.1016/j.jhsb.2004.12.006 ◽

2005 ◽

Vol 30 (3) ◽

pp. 252-264 ◽

Cited By ~ 135

Author(s):

C. JEROSCH-HEROLD

Keyword(s):

Peripheral Nerve ◽

Psychometric Properties ◽

Nerve Injury ◽

Peripheral Nerve Injury ◽

Standardized Test ◽

Nerve Suture ◽

Threshold Test ◽

Injury And Repair ◽

Robust Measures ◽

Monofilament Test

Recovery of sensibility after peripheral nerve injury and repair needs to be assessed using psychometrically robust measures. In this study the literature was reviewed to identify what tests are available to quantify sensibility and to assess their validity, reliability and responsiveness. The databases Medline, CINAHL, Embase and AMED were searched for studies reporting the psychometric properties of sensibility tests. While there is a plethora of tests and studies reporting the outcomes after peripheral nerve suture only a few of the tests have evidence of validity, reliability and responsiveness. Currently the touch threshold test using monofilaments such as the Weinstein Enhanced Sensory Test (WEST) or Semmes–Weinstein Monofilament Test (SWMT) and the shape–texture identification (STI™) test for tactile gnosis are the only tests which meet criteria for a standardized test and have had their psychometric properties evaluated and quantified.

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