Subarachnoid Transplant of a Human Neuronal Cell Line Attenuates Chronic Allodynia and Hyperalgesia After Excitotoxic Spinal Cord Injury in the Rat

Eaton, Mary J.; Wolfe, Stacey Quintero; Martinez, Miguel A.; Hernandez, Massiel; Furst, Cassandra; Huang, Jian; Frydel, Beata R.; Gómez-Marı́n, Orlando

doi:10.1016/j.jpain.2006.05.013

Cited by 51 publications

(68 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, systemic administration of GABA-enhancing drugs is not efficacious for relieving neuropathic pain, as it cannot specifically improve inhibitory neurotransmission in the spinal cord and is associated with significant side effects. Therefore, the idea of grafting of GABA-secreting cells or GABA-ergic neurons directly into the spinal cord has received considerable interest in neuropathic pain models (Eaton et al, 1999a(Eaton et al, , 1999b(Eaton et al, , 2007Mukhida et al, 2007).…”

Section: Gaba-ergic Cell Therapy For Relieving Neuropathic Painmentioning

confidence: 99%

Potential of GABA-ergic cell therapy for schizophrenia, neuropathic pain, and Alzheimer׳s and Parkinson׳s diseases

Shetty

Bates

2016

Brain Research

View full text Add to dashboard Cite

Several neurological and psychiatric disorders present hyperexcitability of neurons in specific regions of the brain or spinal cord, partly because of some loss and/or dysfunction of gammaamino butyric acid positive (GABA-ergic) inhibitory interneurons. Strategies that enhance inhibitory neurotransmission in the affected brain regions may therefore ease several or most deficits linked to these disorders. This perception has incited a huge interest in testing the efficacy of GABA-ergic interneuron cell grafting into regions of the brain or spinal cord exhibiting hyperexcitability, dearth of GABA-ergic interneurons or impaired inhibitory neurotransmission, using preclinical models of neurological and psychiatric disorders. Interneuron progenitors from the embryonic ventral telencephalon capable of differentiating into diverse subclasses of interneurons have particularly received much consideration because of their ability for dispersion, migration and integration with the host neural circuitry after grafting. The goal of this review is to discuss the premise, scope and advancement of GABA-ergic cell therapy for easing neurological deficits in preclinical models of schizophrenia, chronic neuropathic pain, Alzheimer's disease and Parkinson's disease. As grafting studies in these prototypes have so far utilized either primary cells from the embryonic medial and lateral ganglionic eminences or neural progenitor cells expanded from these eminences as donor material, the proficiency of these cell types is highlighted. Moreover, future studies that are essential prior to considering the possible clinical application of these cells for the above neurological conditions are proposed. Particularly, the need for grafting studies utilizing medial ganglionic eminence-like progenitors generated from human pluripotent stem cells via directed differentiation approaches or somatic cells through direct reprogramming methods are emphasized.

show abstract

Section: Gaba-ergic Cell Therapy For Relieving Neuropathic Painmentioning

confidence: 99%

Potential of GABA-ergic cell therapy for schizophrenia, neuropathic pain, and Alzheimer׳s and Parkinson׳s diseases

Shetty

Bates

2016

Brain Research

View full text Add to dashboard Cite

show abstract

“…Previous studies have argued that intrathecal injection for cell transplantation might not be adequate for consistent and sustained engraftment [17], probably because grafted cells were deposited onto the subarachonoid space and survival rates of transplanted cells were very low ($1%) [16]. Therefore, a suggestion has been made to encourage direct transplantation into the spinal cord parenchyma, allowing the cells to settle down and function properly and consistently.…”

Section: Discussionmentioning

confidence: 99%

Transplantation of GABAergic Neurons from ESCs Attenuates Tactile Hypersensitivity Following Spinal Cord Injury

et al. 2010

View full text Add to dashboard Cite

We investigated the therapeutic potential of mouse ESCderived gamma-amino butyric acid (GABA)ergic neurons ($74% of total neurons in vitro) to reduce neuropathic pain following spinal cord injury (SCI) in rats. Spinal cord hemisection at the T13 segment, which is used as a rat SCI pain model, induced tactile hypersensitivity of the hind paw, as evidenced by decreased paw withdrawal thresholds in response to von Frey filaments, and also induced hyperexcitability of wide dynamic range neurons in the lumbar spinal cord in response to natural cutaneous stimuli. At 2 weeks posthemisection, GABAergic neurons (500,000 cells) were transplanted into the subarachnoid space of the spinal lumbar enlargement via a modified lumbar puncture technique. The transplantation of GABAergic neurons led to long-term attenuation of hemisection-induced tactile hypersensitivity and neuronal hyperexcitability as compared with vehicle-treated controls. These attenuations were reversed by the application of bicuculline and CGP52432, GABA-A and GABA-B receptor antagonists, respectively, but not by application of the serotonergic receptor antagonist methylsergide, indicating a specific restoration of spinal GABAergic inhibition. Histological data from sections of the lumbar cord in grafts demonstrated that 43.5% of surviving engrafted cells were neurons and located densely in the lower-medial portion of the dorsal funiculi in the spinal white matter. Among the observed neurons, 26.2% were GABAergic. The results suggest that subarachnoid transplantation of ESC-derived GABAergic neurons appear to restore spinal GABAergic inhibitory tone and can be a promising strategy to treat SCI-induced pain.

show abstract

“…It has been generally accepted that genes of regulatory cytokines (e.g., neurotransmitters and neurotrophic factors) that have the desired therapeutic efficacy may be harnessed to provide long-term pain relief. In rats with SCI, a single subarachnoid injection of hNT2.17 cells potently reversed tactile allodynia and thermal hyperalgesia by acting as a "biologic minipump" to synthesize and release inhibitory neurotransmitters γ-aminobutyric acid (GABA) and glycine in the lumbar subarachnoid space (61). In contrast, Melissa et al (62) suggested that murine embryonic C17.2 NSCs lead to thermal and mechanical forelimb allodynia when transplanted into the injured spinal cord in rats, whereas GDNF-transfected C17.2 NSCs (C17.2/ GDNF) exert an analgesic effect on SCI-related pain by inhibiting neuronal sprouting.…”

Section: Spinal Cord Injury Induced Chronic Painmentioning

confidence: 99%

Stem Cells for the Treatment of Neuropathic Pain

Xie¹,

Yue²,

Guan³

et al. 2017

J Anesth Perioper Med

View full text Add to dashboard Cite

Aim of review:Neuropathic pain induced by injury to the somatosensory system is a great clinical problem. Despite multiple therapeutic strategies, the medical community still faces a challenge to treat neuropathic pain in a complete and definitive way, since the pathogenesis of this hypersensitive state is very complex. Stem cell transplantation may be an important approach for the treatment of neuropathic pain. This article aimed to review important and illustrative results from recent stem cell studies under various neuropathic pain conditions and to interpret their clinical implications for stem cell transplantation. Methods: We reviewed recent articles and literatures about stem cells for the treatment of neuropathic pain, in order to identify the types of stem cells, delivery approaches and the advances of stem cells for the treatment of peripheral nerve injury induced neuropathic pain, painful diabetic peripheral neuropathy and spinal cord injury (SCI) induced chronic pain. Recent findings: Recently, the successful use of stem cell for the treatment of a diverse spectrum of diseases in animals has attracted more attentions from pain scientists. Accumulating evidence has shown that stem cell transplantation has a therapeutic effect on neuropathic pain. Stem cell transplantation can effectively relieve neuropathic pain under different pathological conditions. However, it is interesting to point out that peripheral neuropathic pain seems to be more responsive to stem cell therapy than SCI-induced chronic pain. Moreover, stem cell treatment does not always exert positive results in SCI-induced chronic pain (e.g. aggravating pain above the lesion spinal cord segment). Conclusion:The analgesic effect of stem cells depends on the capacity to offer a multipotent cellular source for replacing injured neural cells and delivering trophic factors to lesion sites. Stem cell researches should focus on both experimental and clinical studies of

show abstract

Subarachnoid Transplant of a Human Neuronal Cell Line Attenuates Chronic Allodynia and Hyperalgesia After Excitotoxic Spinal Cord Injury in the Rat

Cited by 51 publications

References 81 publications

Potential of GABA-ergic cell therapy for schizophrenia, neuropathic pain, and Alzheimer׳s and Parkinson׳s diseases

Potential of GABA-ergic cell therapy for schizophrenia, neuropathic pain, and Alzheimer׳s and Parkinson׳s diseases

Transplantation of GABAergic Neurons from ESCs Attenuates Tactile Hypersensitivity Following Spinal Cord Injury

Stem Cells for the Treatment of Neuropathic Pain

Contact Info

Product

Resources

About