Subarachnoid Adrenal Medullary Transplants for Terminal Cancer Pain A Report of Preliminary Studies

Winnie, Alon P.; Pappas, George D.; Gupta, Tapas K. Das; Wang, Hong; Ortega, John D.; Sagen, Jacqueline

doi:10.1097/00000542-199310000-00004

Cited by 83 publications

(19 citation statements)

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“…The mechanism of adenoviral gene transfer is more like cell transplantation studies which have been reported. For example, retrovirus vectors have been used to transfect and express ␤-endorphin in fibroblasts, 27 and spinal transplantation of adrenal medullary cells which naturally release opioid peptides reduces nocifensive behaviors (tail flick and paw pinch response) 28 and have been reported to decrease experienced pain in humans with pain and terminal cancer; 29 similar results have been demonstrated using the AtT-20 pituitary tumor-derived cell line modified to constitutively secrete enkephalin. 30,31 However, these approaches all rely on release of peptides into CSF, rather than localized release of enkephalin in the dorsal horn.…”

Section: Discussionmentioning

confidence: 69%

Antinociceptive effect of a genomic herpes simplex virus-based vector expressing human proenkephalin in rat dorsal root ganglion

et al. 2001

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Endogenous opiate peptides acting pre-and post-synaptically in the dorsal horn of spinal cord inhibit transmission of nociceptive stimuli. We transfected neurons of the dorsal root ganglion in vivo by footpad inoculation with 30 l (3 × 10 7 p.f.u.) of a replication-incompetent (ICP4-deleted) herpes simplex virus (HSV) vector with a cassette containing a portion of the human proenkephalin gene coding for 5 metand 1 leu-enkephalin molecules under the control of the human cytomegalovirus immediate-early promoter (HCMV IEp) inserted in the HSV thymidine kinase (tk) locus. Vectordirected expression of enkephalin produced a significant

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Section: Discussionmentioning

confidence: 69%

Antinociceptive effect of a genomic herpes simplex virus-based vector expressing human proenkephalin in rat dorsal root ganglion

et al. 2001

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“…The association of spinal enkephalin with the modulation of nociceptive information is further supported by the demonstration that measures that increase enkephalin levels in the spinal cord induce antinociception and reduce pain (Winnie et al, 1993;Wu et al, 1994). Thus, involvement of oestrogen in the regulation of enkephalin expression in the spinal cord might affect nociceptive threshold.…”

Section: Discussionmentioning

confidence: 88%

Colocalization of Oestrogen Receptor lmmunoreactivity and Preproenkephalin mRNA Expression to Neurons in the Superficial Laminae of the Spinal and Medullary Dorsal Horn of Rats

Amandusson

Hermanson

Blomqvist

1996

Eur J of Neuroscience

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A double-labelling procedure combining immunohistochemical staining with in situ hybridization using a radiolabelled cRNA probe was employed to demonstrate oestrogen receptor-like immunoreactivity and preproenkephalin-A mRNA in the medullary and spinal dorsal horn of female rats. Both markers labelled large numbers of neurons in the substantia gelatinosa and its trigeminal homologue. Many of these neurons were double-labelled, displaying both oestrogen receptor-like-immunoreactivity and preproenkephalin-A mRNA; cell counts showed that 40-60% of the of the oestrogen receptor-like-immunoreactive cells in the superficial laminae also were labelled for preproenkephalin-A mRNA, and that 60-70% of the preproenkephalin-A mRNA-labelled neurons in the same laminae displayed oestrogen receptor-like immunoreactivity. Previous studies have shown that oestrogen receptors can bind to the promoter region of the preproenkephalin-A gene, and studies on the hypothalamus have demonstrated that oestrogen regulates enkephalin expression in select neuronal populations. The present results demonstrate that enkephalinergic neurons in the superficial dorsal horn contain oestrogen receptors and suggest that oestrogen may play an important role in the modulation of sensory and nociceptive processing in the lower medulla and spinal cord.

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“…Rather, by integrating into functional circuits, MGE cells overcome a functional deficit that reverses a critical etiology (i.e. defects in endogenous inhibition) of the persistent pain (Eaton et al, 1999; Hao et al, 2005; Liu et al, 2004; Sagen et al, 1990; Winnie et al, 1993; Yu et al, 1998). …”

Section: Discussionmentioning

confidence: 99%

Forebrain GABAergic Neuron Precursors Integrate into Adult Spinal Cord and Reduce Injury-Induced Neuropathic Pain

Bráz

Sharif‐Naeini

Vogt

et al. 2012

Neuron

197

201

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Neuropathic pain is a chronic debilitating disease characterized by mechanical allodynia and spontaneous pain. Because symptoms are often unresponsive to conventional methods of pain treatment, new therapeutic approaches are essential. Here, we describe a strategy that not only ameliorates symptoms of neuropathic pain, but is also potentially disease modifying. We show that transplantation of immature telencephalic GABAergic interneurons from the mouse medial ganglionic eminence (MGE) into the adult mouse spinal cord completely reverses the mechanical hypersensitivity produced by peripheral nerve injury. Underlying this improvement is a remarkable integration of the MGE transplants into the host spinal cord circuitry, in which the transplanted cells make functional connections with both primary afferent and spinal cord neurons. By contrast, MGE transplants were not effective against inflammatory pain. Our findings suggest that MGE-derived GABAergic interneurons overcome the spinal cord hyperexcitability that is a hallmark of nerve-injury induced neuropathic pain.

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Subarachnoid Adrenal Medullary Transplants for Terminal Cancer Pain A Report of Preliminary Studies

Cited by 83 publications

References 0 publications

Antinociceptive effect of a genomic herpes simplex virus-based vector expressing human proenkephalin in rat dorsal root ganglion

Antinociceptive effect of a genomic herpes simplex virus-based vector expressing human proenkephalin in rat dorsal root ganglion

Colocalization of Oestrogen Receptor lmmunoreactivity and Preproenkephalin mRNA Expression to Neurons in the Superficial Laminae of the Spinal and Medullary Dorsal Horn of Rats

Forebrain GABAergic Neuron Precursors Integrate into Adult Spinal Cord and Reduce Injury-Induced Neuropathic Pain

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