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.

Miami VA Health System Center, D806C, 1201 NW 16th Street, Miami, FL 33199, USA.
Pain research and treatment 01/2012; 2012:356412. DOI: 10.1155/2012/356412
Source: PubMed

ABSTRACT 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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Pain medicine is one of the most rapidly developing medical specialties of today. While there are many modalities that can be used in managing the patient in pain, drug treatment remains, for the most part, the cornerstone of treatment. Opioids retain their position as the foundation of most analgesic strategies, although they tend to be used nowadays in combination with adjuvant analgesics such as paracetamol and nonsteroidal antiinflammatory drugs. The range of available opioids has also been expanded with drugs such as hydromorphone and oxycodone, originally developed almost a century ago. This expanded choice has resulted in the concept of opioid rotation in chronic pain states, an approach that is aimed at maintaining pain control while minimizing adverse effects. Nonsteroidal antiinflammatory drugs continue to play an important role, especially as adjuvants, and the development of drugs such as celecoxib and refecoxib, highly specific for the inhibition of cyclooxygenase 2 pathway has been a further advance. The treatment of neuropathic pain continues to be a challenge to the clinician. While this has traditionally been treated with drugs from the anticonvulsant, antiarrhythmic and anti-depressant groups, results from these treatments have often been less than satisfactory. This has led to the development of completely new drug classes that modulate neuronal transmission in pain pathways, some of which are derived from exotic animal sources, such as the conotoxins from the marine snail family and epibatidine from a species of frog. The role of cannabinoids remains controversial.
    Drugs of today (Barcelona, Spain: 1998) 03/2002; 38(2):135-45. · 1.00 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: An overview is presented of neuropathic pain syndromes, their characteristic symptoms and signs, and recent approaches to identifying their pathophysiologic mechanisms. The results of recent clinical studies of neuropathic pain are reviewed. Chronic neuropathic pain syndromes are emphasized because these long-lasting and often disabling conditions present a much greater challenge for the clinician than acute pain. Peripheral neuropathic syndromes have received greater attention in the research literature than central pain, and studies of syndromes such as postherpetic neuralgia and painful diabetic neuropathy provide the basis for current knowledge of neuropathic pain. Precise estimates of the prevalence of neuropathic pain are not available, but chronic neuropathic pain may be much more common than has generally been appreciated and its prevalence can be expected to increase in the future. There is considerable agreement that both peripheral and central processes contribute to many chronic neuropathic pain syndromes, and that these different mechanisms may explain the qualitatively different symptoms and signs that patients experience. The limitations of existing treatments for neuropathic pain and the inability to provide relief for many patients has stimulated ongoing studies that examine different approaches to preventing neuropathic pain.
    Clinical Journal of Pain 01/2002; 18(6):343-9. · 2.70 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Indications for strong opioids for cancer-related pain as well as for chronic non-cancer pain are that non-opioid drugs, and other less risky therapies, fail and that the pain is opioid-sensitive. The WHO analgesic ladder principle continues to serve as an excellent educational tool in the efforts by WHO in collaboration with the World Federation of Societies of Anaesthesiologists (WFSA) and The International Association for the Study of Pain (IASP) to increase knowledge of pharmacological pain therapy and increase availability of essential opioid analgesics world-wide. Opioids differ in pharmacodynamics and pharmacokinetics, and patients have different pharmacogenetics and pain mechanisms. Sequential trials of the increasing numbers of available opioid drugs are therefore appropriate when oral morphine fails. Controversies continue concerning diagnosis and handling of opioid-insensitive pain in cancer and chronic non-cancer pain, opioid-induced neurotoxicities, risks of tolerance, addiction, pseudo-addiction, and methods for improving effectiveness and decreasing adverse effects of long-term opioid therapy, treating breakthrough pain with immediate release oral and transmucosal opioids. Consensus guidelines have recently been developed in the Nordic countries concerning the ethical practice of palliative sedation when opioids and other pain-relieving therapies fail in patients soon to die. Guidelines for long-term treatment with strong opioids of chronic non-cancer-related pain are also being developed in the Nordic countries, where very diverging traditions for the usage of such therapy still exist.
    Acta Anaesthesiologica Scandinavica 11/2001; 45(9):1059-66. · 2.31 Impact Factor

Full-text (2 Sources)

Available from
May 16, 2014