scholarly journals Potential for Cell-Transplant Therapy with Human Neuronal Precursors to Treat Neuropathic Pain in Models of PNS and CNS Injury: Comparison of hNT2.17 and hNT2.19 Cell Lines

2012 ◽  
Vol 2012 ◽  
pp. 1-31 ◽  
Author(s):  
Mary J. Eaton ◽  
Yerko Berrocal ◽  
Stacey Q. Wolfe
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Chronic Pain ◽  
Neuropathic Pain ◽  
Cell Lines ◽  
Treatment Modalities ◽  
Cell Transplant ◽  
Cns Injury ◽  
Cord Injury ◽  
Neuronal Precursors

Effective treatment of sensory neuropathies in peripheral neuropathies and spinal cord injury (SCI) is one of the most difficult problems in modern clinical practice. Cell therapy to release antinociceptive agents near the injured spinal cord is a logical next step in the development of treatment modalities. But few clinical trials, especially for chronic pain, have tested the potential of transplant of cells to treat chronic pain. Cell lines derived from the human neuronal NT2 cell line parentage, the hNT2.17 and hNT2.19 lines, which synthesize and release the neurotransmitters gamma-aminobutyric acid (GABA) and serotonin (5HT), respectively, have been used to evaluate the potential of cell-based release of antinociceptive agents near the lumbar dorsal (horn) spinal sensory cell centers to relieve neuropathic pain after PNS (partial nerve and diabetes-related injury) and CNS (spinal cord injury) damage in rat models. Both cell lines transplants potently and permanently reverse behavioral hypersensitivity without inducing tumors or other complications after grafting. Functioning as cellular minipumps for antinociception, human neuronal precursors, like these NT2-derived cell lines, would likely provide a useful adjuvant or replacement for current pharmacological treatments for neuropathic pain.

scholarly journals Neuropathic Pain Related with Spinal Disorders: A Systematic Review

2017 ◽  
Vol 11 (4) ◽  
pp. 661-674 ◽  
Author(s):  
Kwang-Sup Song ◽  
Jae Hwan Cho ◽  
Jae-Young Hong ◽  
Jae Hyup Lee ◽  
Hyun Kang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Disc Herniation ◽  
Treatment Guidelines ◽  
Epidural Block ◽  
Treatment Modalities ◽  
High Quality ◽  
Spinal Disorders ◽  
Cord Injury

<p>Systematic literature review. To review the evidence from high-quality studies regarding the treatment of neuropathic pain originating specifically from spinal disorders. In general, treatment guidelines for neuropathic pain cover all its various causes, including medical disease, peripheral neuropathy, and cancer. However, the natural history of neuropathic pain originating from spinal disorders may differ from that of the pain originating from other causes or lesions. An expert research librarian used terms related to neuropathic pain and spinal disorders, disc herniation, stenosis, and spinal cord injury to search in MEDLINE, Embase, and Cochrane CENTRAL for primary research from January 2000 to October 2015. Among 2,313 potential studies of interest, 25 randomized controlled trials (RCTs) and 21 systematic reviews (SRs) were included in the analysis. The selection was decided based on the agreement of two orthopedic surgeons. There was a lack of evidence about medication for radiculopathy arising from disc herniation and stenosis, but intervention procedures, including epidural block, showed positive efficacy in radiculopathy and also limited efficacy in spinal stenosis. There was some evidence based on the short-term follow-up regarding surgery being superior to conservative treatments for radiculopathy and stenosis. There was limited evidence regarding the efficacy of pharmacological and electric or magnetic stimulation therapies for neuropathic pain after spinal cord injury. This review of RCTs and SRs with high-quality evidence found some evidence regarding the efficacy of various treatment modalities for neuropathic pain related specifically to spinal disorders. However, there is a need for much more supportive evidence.</p>

Role of Microglia and Astrocytes in Spinal Cord Injury Induced Neuropathic Pain

2021 ◽  
pp. 097275312110463
Author(s):  
Gurwattan S. Miranpuri ◽  
Parul Bali ◽  
Justyn Nguyen ◽  
Jason J Kim ◽  
Shweta Modgil ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Spinal Cord Injuries ◽  
Medical Condition ◽  
The United States ◽  
Current Treatment ◽  
Treatment Modalities ◽  
Cord Injury

Spinal cord injuries incite varying degrees of symptoms in patients, ranging from weakness and incoordination to paralysis. Common amongst spinal cord injury (SCI) patients, neuropathic pain (NP) is a debilitating medical condition. Unfortunately, there remain many clinical impediments in treating NP because there is a lack of understanding regarding the mechanisms behind SCI-induced NP (SCINP). Given that more than 450,000 people in the United States alone suffer from SCI, it is unsatisfactory that current treatments yield poor results in alleviating and treating NP. In this review, we briefly discussed the models of SCINP along with the mechanisms of NP progression. Further, current treatment modalities are herein explored for SCINP involving pharmacological interventions targeting glia cells and astrocytes. The studies presented in this review provide insight for new directions regarding SCINP alleviation. Given the severity and incapacitating effects of SCINP, it is imperative to study the pathways involved and find new therapeutic targets in coordination with stem cell research, and to develop a new gold-standard in SCINP treatment.

scholarly journals A Primary Care Provider’s Guide to Pain After Spinal Cord Injury: Screening and Management

2020 ◽  
Vol 26 (3) ◽  
pp. 133-143
Author(s):  
Jithin Varghese ◽  
Kim D. Anderson ◽  
Eva Widerström-Noga ◽  
Upender Mehan
Keyword(s):  
Primary Care ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Chronic Pain ◽  
Treatment Options ◽  
Primary Care Providers ◽  
Assessment Tools ◽  
Treatment Modalities ◽  
Care Providers ◽  
Cord Injury

Individuals with spinal cord injury (SCI) often experience chronic pain as a secondary complication. It can significantly impair mental health, sleep, mood, and overall quality of life. It is important for providers within a primary care setting to recognize the different types of pain such as nociceptive and neuropathic. Various assessment tools are available to guide proper classification and subsequent management. Providers need to have a good knowledge base, structure, and patient focus when managing care. Nonpharmacological interventions are just as important and should be explored prior to or along with pharmacological interventions. Treatment modalities such as physical therapy, exercise, acupuncture, and cognitive behavioral therapy should be tailored to the individual to the greatest extent possible. Gabapentin, pregabalin, and amitriptyline have been studied extensively and are the first-line pharmacological agents for neuropathic pain. It is important to involve patients as equal stakeholders in any pain intervention with adequate lifelong follow-up. The aim of this article is to offer an overview of pain assessment, information, patient interaction, and treatment options available. Although chronic pain has remained difficult to treat successfully, primary care providers can play an integral role in delivering evidence-based and patient-centered care for managing chronic pain among individuals with SCI.

scholarly journals LPA receptor signaling as a therapeutic target for radical treatment of neuropathic pain and fibromyalgia

2020 ◽  
Vol 10 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Hiroshi Ueda
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Chronic Pain ◽  
Neuropathic Pain ◽  
Lysophosphatidic Acid ◽  
Receptor Signaling ◽  
Acidic Stress ◽  
Wide Spread ◽  
Lpa Receptor ◽  
Cord Injury

Since the first discovery that the bioactive lipid, lysophosphatidic acid (LPA) and LPA1 receptor signaling play a role in the initiation of neuropathic pain (NeuP), accumulated reports have supported the original findings and extended the study toward possible therapeutic applications. The present review describes beneficial roles of LPA receptor signaling in a variety of chronic pain, such as peripheral NeuP induced by nerve injury, chemotherapy and diabetes, central NeuP induced by cerebral ischemia with hemorrhage and spinal cord injury, and fibromyalgia-like wide spread pain induced by repeated cold, psychological and muscular acidic stress. Emerging mechanistic findings are the feed-forward amplification of LPA production through LPA1, LPA3 and microglia and the evidence for maintenance of chronic pain by LPA receptor signaling.

scholarly journals Initial Characterization of the Transplant of Immortalized Chromaffin Cells for the Attenuation of Chronic Neuropathic Pain

2000 ◽  
Vol 9 (5) ◽  
pp. 637-656 ◽  
Author(s):  
M. J. Eaton ◽  
M. Martinez ◽  
S. Karmally ◽  
T. Lopez ◽  
J. Sagen
Keyword(s):  
Spinal Cord ◽  
Chronic Pain ◽  
Neuropathic Pain ◽  
Cell Lines ◽  
Subarachnoid Space ◽  
Chromaffin Cells ◽  
Chromaffin Cell ◽  
Permissive Temperature ◽  
Cord Injury

Cultures of embryonic day 17 (E17) rat adrenal and neonatal bovine adrenal cells were conditionally immortalized with the temperature-sensitive allele of SV40 large T antigen (tsTag) and chromaffin cell lines established. Indicative of the adrenal chromaffin phenotype, these cells expressed immunoreactivity (ir) for tyrosine hydroxylase (TH), the first enzyme in the synthetic pathway for catecholamines. At permissive temperature in vitro (33°C), these chromaffin cells are proliferative, have a typical rounded chromaffin-like morphology, and contain detectable TH-ir. At nonpermissive temperature in vitro (39°C), these cells stop proliferating and express increased TH-ir. When these immortalized chromaffin cells were transplanted in the lumbar subarachnoid space of the spinal cord 1 week after a unilateral chronic constriction injury (CCI) of the rat sciatic nerve, they survived longer than 7 weeks on the pia mater around the spinal cord and continued to express TH-ir. Conversely, grafted chromaffin cells lost Tag-ir after transplant and Tag-ir was undetectible in the grafts after 7 weeks in the subarachnoid space. At no time did the grafts form tumors after transplant into the host animals. These grafted chromaffin cells also expressed immunoreactivities for the other catecholamine-synthesizing enzymes 7 weeks after grafting, including: dopamine-β-hydroxylase (DβH) and phenylethanolamine-N-methyltransferase (PNMT). The grafted cells also expressed detectable immunoreactivities for the opioid met-enkephalin (ENK), the peptide galanin (GAL), and the neurotransmitters γ-aminobutyric acid (GABA) and serotonin (5-HT). Furthermore, after transplantation, tactile and cold allodynia and tactile and thermal hyperalgesia induced by CCI were significantly reduced during a 2–8-week period, related to the chromaffin cell transplants. The maximal antinociceptive effect occurred 1–3 weeks after grafting. Control adrenal fibroblasts, similarly immortalized and similarly transplanted after CCI, did not express any of the chromaffin antigenic markers, and fibroblast grafts had no effect on the allodynia and hyperalgesia induced by CCI. These data suggest that embryonic and neonatal chromaffin cells can be conditionally immortalized and will continue to express the phenotype of primary chromaffin cells in vitro and in vivo; grafted cells will ameliorate neuropathic pain after nerve injury and can be used as a homogeneous source to examine the mechanisms by which chromaffin transplants reverse chronic pain. The use of such chromaffin cell lines that are able to deliver antinociceptive molecules in models of chronic pain after nerve and spinal cord injury (SCI) offers a novel approach to pain management.

scholarly journals 1-kHz high-frequency spinal cord stimulation alleviates chronic refractory pain after spinal cord injury: a case report

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Chiaki Yamada ◽  
Aiko Maeda ◽  
Katsuyuki Matsushita ◽  
Shoko Nakayama ◽  
Kazuhiro Shirozu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Spinal Cord Stimulation ◽  
High Frequency ◽  
Cervical Vertebrae ◽  
Intractable Pain ◽  
Target Area ◽  
Positive Effects ◽  
Cord Injury

Abstract Background Patients with spinal cord injury (SCI) frequently complain of intractable pain that is resistant to conservative treatments. Here, we report the successful application of 1-kHz high-frequency spinal cord stimulation (SCS) in a patient with refractory neuropathic pain secondary to SCI. Case presentation A 69-year-old male diagnosed with SCI (C4 American Spinal Injury Association Impairment Scale A) presented with severe at-level bilateral upper extremity neuropathic pain. Temporary improvement in his symptoms with a nerve block implied peripheral component involvement. The patient received SCS, and though the tip of the leads could not reach the cervical vertebrae, a 1-kHz frequency stimulus relieved the intractable pain. Conclusions SCI-related symptoms may include peripheral components; SCS may have a considerable effect on intractable pain. Even when the SCS electrode lead cannot be positioned in the target area, 1-kHz high-frequency SCS may still produce positive effects.

Aging and miR-155 in mice influence survival and neuropathic pain after spinal cord injury

2021 ◽  
Author(s):  
Andrew D. Gaudet ◽  
Laura K. Fonken ◽  
Monica T. Ayala ◽  
Steven F. Maier ◽  
Linda R. Watkins
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuropathic Pain ◽  
Cord Injury
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