-
International Journal of Molecular... Feb 2020Degenerative disc disease is a leading cause of chronic back pain in the aging population in the world. Sinuvertebral nerve and basivertebral nerve are postulated to be... (Review)
Review
Lumbar Degenerative Disease Part 1: Anatomy and Pathophysiology of Intervertebral Discogenic Pain and Radiofrequency Ablation of Basivertebral and Sinuvertebral Nerve Treatment for Chronic Discogenic Back Pain: A Prospective Case Series and Review of Literature.
Degenerative disc disease is a leading cause of chronic back pain in the aging population in the world. Sinuvertebral nerve and basivertebral nerve are postulated to be associated with the pain pathway as a result of neurotization. Our goal is to perform a prospective study using radiofrequency ablation on sinuvertebral nerve and basivertebral nerve; evaluating its short and long term effect on pain score, disability score and patients' outcome. A review in literature is done on the pathoanatomy, pathophysiology and pain generation pathway in degenerative disc disease and chronic back pain. 30 patients with 38 levels of intervertebral disc presented with discogenic back pain with bulging degenerative intervertebral disc or spinal stenosis underwent Uniportal Full Endoscopic Radiofrequency Ablation application through either Transforaminal or Interlaminar Endoscopic Approaches. Their preoperative characteristics are recorded and prospective data was collected for Visualized Analogue Scale, Oswestry Disability Index and MacNab Criteria for pain were evaluated. There was statistically significant Visual Analogue Scale improvement from preoperative state at post-operative 1wk, 6 months and final follow up were 4.4 ± 1.0, 5.5 ± 1.2 and 5.7 ± 1.3, respectively, < 0.0001. Oswestery Disability Index improvement from preoperative state at 1week, 6 months and final follow up were 45.8 ± 8.7, 50.4 ± 8.2 and 52.7 ± 10.3, < 0.0001. MacNab criteria showed excellent outcomes in 17 cases, good outcomes in 11 cases and fair outcomes in 2 cases Sinuvertebral Nerve and Basivertebral Nerve Radiofrequency Ablation is effective in improving the patients' pain, disability status and patient outcome in our study.
Topics: Adolescent; Adult; Aged; Back Pain; Catheter Ablation; Chronic Pain; Female; Humans; Intervertebral Disc Degeneration; Lumbar Vertebrae; Male; Middle Aged; Prospective Studies; Spinal Nerves
PubMed: 32098249
DOI: 10.3390/ijms21041483 -
Neuron Oct 2020Primary somatosensory neurons are specialized to transmit specific types of sensory information through differences in cell size, myelination, and the expression of...
Primary somatosensory neurons are specialized to transmit specific types of sensory information through differences in cell size, myelination, and the expression of distinct receptors and ion channels, which together define their transcriptional and functional identity. By profiling sensory ganglia at single-cell resolution, we find that all somatosensory neuronal subtypes undergo a similar transcriptional response to peripheral nerve injury that both promotes axonal regeneration and suppresses cell identity. This transcriptional reprogramming, which is not observed in non-neuronal cells, resolves over a similar time course as target reinnervation and is associated with the restoration of original cell identity. Injury-induced transcriptional reprogramming requires ATF3, a transcription factor that is induced rapidly after injury and necessary for axonal regeneration and functional recovery. Our findings suggest that transcription factors induced early after peripheral nerve injury confer the cellular plasticity required for sensory neurons to transform into a regenerative state.
Topics: Activating Transcription Factor 3; Animals; Axons; Axotomy; Cellular Reprogramming; Crush Injuries; Ganglia, Spinal; Gene Expression Regulation; Lumbar Vertebrae; Mechanoreceptors; Mice; Nerve Regeneration; Neuralgia; Neuronal Plasticity; Nociceptors; Peripheral Nerve Injuries; RNA-Seq; Recovery of Function; Sciatic Nerve; Sensory Receptor Cells; Single-Cell Analysis; Spinal Nerves; Transcriptome
PubMed: 32810432
DOI: 10.1016/j.neuron.2020.07.026 -
Neuroscience Bulletin Mar 2021Chemokines and receptors have been implicated in the pathogenesis of chronic pain. Here, we report that spinal nerve ligation (SNL) increased CXCR3 expression in dorsal...
Chemokines and receptors have been implicated in the pathogenesis of chronic pain. Here, we report that spinal nerve ligation (SNL) increased CXCR3 expression in dorsal root ganglion (DRG) neurons, and intra-DRG injection of Cxcr3 shRNA attenuated the SNL-induced mechanical allodynia and heat hyperalgesia. SNL also increased the mRNA levels of CXCL9, CXCL10, and CXCL11, whereas only CXCL10 increased the number of action potentials (APs) in DRG neurons. Furthermore, in Cxcr3 mice, CXCL10 did not increase the number of APs, and the SNL-induced increase of the numbers of APs in DRG neurons was reduced. Finally, CXCL10 induced the activation of p38 and ERK in ND7-23 neuronal cells and DRG neurons. Pretreatment of DRG neurons with the P38 inhibitor SB203580 decreased the number of APs induced by CXCL10. Our data indicate that CXCR3, activated by CXCL10, mediates p38 and ERK activation in DRG neurons and enhances neuronal excitability, which contributes to the maintenance of neuropathic pain.
Topics: Animals; Ganglia, Spinal; Hyperalgesia; Mice; Neuralgia; Rats; Rats, Sprague-Dawley; Spinal Nerves
PubMed: 33196963
DOI: 10.1007/s12264-020-00608-1 -
Neuron Jan 2022Spontaneous pain refers to pain occurring without external stimuli. It is a primary complaint in chronic pain conditions and remains difficult to treat. Moreover, the...
Spontaneous pain refers to pain occurring without external stimuli. It is a primary complaint in chronic pain conditions and remains difficult to treat. Moreover, the mechanisms underlying spontaneous pain remain poorly understood. Here we employed in vivo imaging of dorsal root ganglion (DRG) neurons and discovered a distinct form of abnormal spontaneous activity following peripheral nerve injury: clusters of adjacent DRG neurons firing synchronously and sporadically. The level of cluster firing correlated directly with nerve injury-induced spontaneous pain behaviors. Furthermore, we demonstrated that cluster firing is triggered by activity of sympathetic nerves, which sprout into DRGs after injury, and identified norepinephrine as a key neurotransmitter mediating this unique firing. Chemogenetic and pharmacological manipulations of sympathetic activity and norepinephrine receptors suggest that they are necessary and sufficient for DRG cluster firing and spontaneous pain behavior. Therefore, blocking sympathetically mediated cluster firing may be a new paradigm for treating spontaneous pain.
Topics: Ganglia, Spinal; Humans; Pain; Sensory Receptor Cells; Spinal Nerves; Sympathetic Nervous System
PubMed: 34752775
DOI: 10.1016/j.neuron.2021.10.019 -
CNS Neuroscience & Therapeutics Sep 2019Previous studies have demonstrated that the CXCL12/CXCR4 signaling axis is involved in the regulation of neuropathic pain (NP). Here, we performed experiments to test...
BACKGROUND
Previous studies have demonstrated that the CXCL12/CXCR4 signaling axis is involved in the regulation of neuropathic pain (NP). Here, we performed experiments to test whether the CXCL12/CXCR4 signaling pathway contributes to the pathogenesis of neuropathic pain after spinal nerve ligation (SNL) via central sensitization mechanisms.
METHODS
Neuropathic pain was induced and assessed in a SNL rat model. The expression and distribution of CXCL12 or CXCR4 were examined by immunofluorescence staining and western blot. The effects of CXCL12 rat peptide, CXCL12 neutralizing antibody, CXCR4 antagonist, and astrocyte metabolic inhibitor on pain hypersensitivity were explored by behavioral tests in naive or SNL rats. We measured the expression level of c-Fos and CGRP to evaluate the sensitization of neurons by RT-PCR. The activation of astrocyte and microglia was analyzed by measuring the level of GFAP and iba-1. The mRNA levels of the pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 and Connexin 30, Connexin 43, EAAT 1, EAAT 2 were also detected by RT-PCR.
RESULTS
First, we found that the expression of CXCL12 and CXCR4 was upregulated after SNL. CXCL12 was mainly expressed in the neurons while CXCR4 was expressed both in astrocytes and neurons in the spinal dorsal horn after SNL. Moreover, intrathecal administration of rat peptide, CXCL12, induced hypersensitivity in naive rats, which was partly reversed by fluorocitrate. In addition, the CXCL12 rat peptide increased mRNA levels of c-Fos, GFAP, and iba-1. A single intrathecal injection of CXCL12 neutralizing antibody transiently reversed neuropathic pain in the SNL rat model. Consecutive use of CXCL12 neutralizing antibody led to significant delay in the induction of neuropathic pain, and reduced the expression of GFAP and iba-1 in the spinal dorsal horn. Finally, repeated intrathecal administration of the CXCR4 antagonist, AMD3100, significantly suppressed the initiation and duration of neuropathic pain. The mRNA levels of c-Fos, CGRP, GFAP, iba-1, and pro-inflammatory cytokines, also including Connexin 30 and Connexin 43 were decreased after injection of AMD3100, while EAAT 1 and EAAT 2 mRNAs were increased.
CONCLUSION
We demonstrate that the CXCL12/CXCR4 signaling pathway contributes to the development and maintenance of neuropathic pain via central sensitization mechanisms. Importantly, intervening with CXCL12/CXCR4 presents an effective therapeutic approach to treat the neuropathic pain.
Topics: Animals; Benzylamines; Central Nervous System Sensitization; Chemokine CXCL12; Cyclams; Heterocyclic Compounds; Ligation; Male; Neuralgia; Rats; Rats, Sprague-Dawley; Receptors, CXCR4; Signal Transduction; Spinal Cord; Spinal Nerves
PubMed: 30955244
DOI: 10.1111/cns.13128 -
Journal of Anatomy Apr 2018A prominent anatomical feature of the peripheral nervous system is the segmentation of mixed (motor, sensory and autonomic) spinal nerves alongside the spinal cord.... (Review)
Review
A prominent anatomical feature of the peripheral nervous system is the segmentation of mixed (motor, sensory and autonomic) spinal nerves alongside the spinal cord. During early development their axon growth cones avoid the developing vertebral elements by traversing the anterior/cranial half of each somite-derived sclerotome, so ensuring the separation of spinal nerves from vertebral bones as axons extend towards their peripheral targets. A glycoprotein expressed on the surface of posterior half-sclerotome cells confines growth cones to the anterior half-sclerotomes by contact repulsion. A closely similar glycoprotein is expressed in avian and mammalian grey matter, where we hypothesize it may have evolved to regulate neural plasticity in birds and mammals.
Topics: Animals; Body Patterning; Chick Embryo; Growth Cones; Humans; Mice; Nerve Growth Factor; Somites; Spinal Cord; Spinal Nerves; Spine
PubMed: 29063597
DOI: 10.1111/joa.12714 -
Cells Jul 2021Complete spinal cord injury (SCI) leads to permanent motor, sensitive and sensory deficits. In humans, there is currently no therapy to promote recovery and the only... (Review)
Review
Complete spinal cord injury (SCI) leads to permanent motor, sensitive and sensory deficits. In humans, there is currently no therapy to promote recovery and the only available treatments include surgical intervention to prevent further damage and symptomatic relief of pain and infections in the acute and chronic phases, respectively. Basically, the spinal cord is classically viewed as a nonregenerative tissue with limited plasticity. Thereby the establishment of the "glial" scar which appears within the SCI is mainly described as a hermetic barrier for axon regeneration. However, recent discoveries have shed new light on the intrinsic functional plasticity and endogenous recovery potential of the spinal cord. In this review, we will address the different aspects that the spinal cord plasticity can take on. Indeed, different experimental paradigms have demonstrated that axonal regrowth can occur even after complete SCI. Moreover, recent articles have demonstrated too that the "glial" scar is in fact composed of several cellular populations and that each of them exerts specific roles after SCI. These recent discoveries underline the underestimation of the plasticity of the spinal cord at cellular and molecular levels. Finally, we will address the modulation of this endogenous spinal cord plasticity and the perspectives of future therapeutic opportunities which can be offered by modulating the injured spinal cord microenvironment.
Topics: Animals; Humans; Nerve Regeneration; Neural Stem Cells; Neuroglia; Neuronal Plasticity; Phenotype; Recovery of Function; Spinal Cord; Spinal Cord Injuries; Spinal Nerves
PubMed: 34440655
DOI: 10.3390/cells10081886 -
Turkish Neurosurgery 2019To seek the efficacy of selective spinal nerve blocks in the treatment of groin pain that are irresponsive to peripheral nerve blocks.
AIM
To seek the efficacy of selective spinal nerve blocks in the treatment of groin pain that are irresponsive to peripheral nerve blocks.
MATERIAL AND METHODS
This retrospective study comprised 17 patients with ilioinguinal, iliohypogastric, and genitofemoral neuralgias treated between 2017 and 2018.
RESULTS
All patients received diagnostic peripheral nerve blocks and/or TAP blocks with blind or ultrasound-guided techniques. Four patients had ineffectual peripheral nerve blocks, after which they underwent T12 and L1 selective spinal nerve blocks. All four patients had satisfactory results.
CONCLUSION
If distal peripheral nerve blocks are ineffective, an upper level nerve lesion, a lesion in the lumbar plexus or an L1 radiculopathy should be considered in ilioinguinal, iliohypogastric, and genitofemoral neuralgias. Upper level nerve blocks should be performed before deciding on surgery.
Topics: Adult; Anesthesia, Spinal; Autonomic Nerve Block; Female; Femoral Neuropathy; Humans; Lumbosacral Plexus; Male; Middle Aged; Neuralgia; Peripheral Nerves; Retrospective Studies; Spinal Nerves
PubMed: 30829381
DOI: 10.5137/1019-5149.JTN.23990-18.1 -
Scientific Reports Apr 2020The avian transition from long to short, distally fused tails during the Mesozoic ushered in the Pygostylian group, which includes modern birds. The avian tail embodies...
The avian transition from long to short, distally fused tails during the Mesozoic ushered in the Pygostylian group, which includes modern birds. The avian tail embodies a bipartite anatomy, with the proximal separate caudal vertebrae region, and the distal pygostyle, formed by vertebral fusion. This study investigates developmental features of the two tail domains in different bird groups, and analyzes them in reference to evolutionary origins. We first defined the early developmental boundary between the two tail halves in the chicken, then followed major developmental structures from early embryo to post-hatching stages. Differences between regions were observed in sclerotome anterior/posterior polarity and peripheral nervous system development, and these were consistent in other neognathous birds. However, in the paleognathous emu, the neognathous pattern was not observed, such that spinal nerve development extends through the pygostyle region. Disparities between the neognaths and paleognaths studied were also reflected in the morphology of their pygostyles. The ancestral long-tailed spinal nerve configuration was hypothesized from brown anole and alligator, which unexpectedly more resembles the neognathous birds. This study shows that tail anatomy is not universal in avians, and suggests several possible scenarios regarding bird evolution, including an independent paleognathous long-tailed ancestor.
Topics: Alligators and Crocodiles; Animals; Chick Embryo; Chickens; Embryonic Development; Fossils; Genetic Speciation; Lizards; Phylogeny; Spinal Nerves; Tail
PubMed: 32286419
DOI: 10.1038/s41598-020-63264-5 -
Pain Physician May 2017Spinal nerve-ligated neuropathy and chemotherapy-induced neuropathy produce a persistent tactile allodynia in mice. Tianeptine is an antidepressant that exhibits...
BACKGROUND
Spinal nerve-ligated neuropathy and chemotherapy-induced neuropathy produce a persistent tactile allodynia in mice. Tianeptine is an antidepressant that exhibits structural similarities to tricyclic antidepressants but has distinct neurochemical properties.
OBJECTIVE
Here we examined the effects of intraperitoneal (i.p.) tianeptine on allodynia in spinal nerve-ligated and chemotherapy-induced neuropathic mice.
STUDY DESIGN
A randomized, experimental trial.
SETTING
Laboratory animal study.
METHODS
Spinal nerve-ligated neuropathy was induced in a Chung model made by ligating the L5 spinal nerve. Chemotherapy-induced neuropathy was induced by injecting vincristine (0.1 mg/kg/day; i.p.) on the following schedule: 5 days on, 2 days off, for14 days. Tianeptine (10, 30, and 50 mg/kg) and saline were administered, respectively, to both groups of neuropathic mice (n = 5 for each group). We evaluated mechanical allodynia using von Frey hairs prior to drug injections and at 30, 60, 90, 120, 180, and 240 minutes, and 24 hours after injections. We also measured the changes in activate transcription factor 3 (ATF3) level in the dorsal root ganglion (DRG) in each group in order to understand the analgesic mechanism of tianeptine.
RESULTS
Both spinal nerve-ligated and chemotherapy-induced neuropathic mice showed prominent allodynia. The control group showed no differences in mechanically induced allodynia compared to the experimental groups. For the tianeptine groups, paw-withdrawal thresholds in response to mechanical stimuli were significantly lower than the pre-administration values and values from the control group (P < 0.05). The increase in DRG ATF3 in neuropathic mice was reduced by tianeptine (P < 0.05).
LIMITATIONS
Less is known about the transcription factors that affect inflammation signaling.
CONCLUSIONS
Tianeptine administered i.p. reduces mechanical allodynia in spinal nerve-ligated and chemotherapy-induced neuropathic mice models. These effects were confirmed by attenuation of previously increased DRG ATF3.
Topics: Activating Transcription Factor 3; Analgesics; Animals; Disease Models, Animal; Ganglia, Spinal; Hyperalgesia; Male; Mice; Mice, Inbred C57BL; Neuralgia; Rats, Sprague-Dawley; Spinal Nerves; Thiazepines; Vincristine
PubMed: 28535568
DOI: No ID Found