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 04/2012; 2012(2090-1542):356412. DOI: 10.1155/2012/356412
Source: PubMed


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.

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    ABSTRACT: Changes in descending serotonergic innervation of spinal neural activity have been implicated in symptoms of paralysis, spasticity, sensory disturbances and pain following spinal cord injury (SCI). Serotonergic neurons possess an enhanced ability to regenerate or sprout after many types of injury, including SCI. Current research suggests that serotonine (5-HT) release within the ventral horn of the spinal cord plays a critical role in motor function, and activation of 5-HT receptors mediates locomotor control. 5-HT originating from the brain stem inhibits sensory afferent transmission and associated spinal reflexes; by abolishing 5-HT innervation SCI leads to a disinhibition of sensory transmission. 5-HT denervation supersensitivity is one of the key mechanisms underlying the increased motoneuron excitability that occurs after SCI, and this hyperexcitability has been demonstrated to underlie the pathogenesis of spasticity after SCI. Moreover, emerging evidence implicates serotonergic descending facilitatory pathways from the brainstem to the spinal cord in the maintenance of pathologic pain. There are functional relevant connections between the descending serotonergic system from the rostral ventromedial medulla in the brainstem, the 5-HT receptors in the spinal dorsal horn, and the descending pain facilitation after tissue and nerve injury. This narrative review focussed on the most important studies that have investigated the above-mentioned effects of impaired 5-HT-transmission in humans after SCI. We also briefly discussed the promising therapeutical approaches with serotonergic drugs, monoclonal antibodies and intraspinal cell transplantation.
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    ABSTRACT: Our objective is to analyze and observe the different administration routes of parecoxib sodium pretreatment on the behavioral improvement of rats with neuropathic pain to provide the preclinical data of parecoxib sodium on neuropathic pain treatment. 30 SD rats were randomly divided into five groups, including model group, sham operation group, intrathecal injection group (IT group), intraperitoneal injection group (IP group), and perineural infiltration group (PI group). The rats in model group and three parecoxib sodium pretreatment groups received spinal nerve ligation (SNL). Heat pain test and 50 % paw mechanical withdrawal threshold test (50 % PMWT) were use to assess the responses after parecoxib sodium pretreatment. 50 % PMWT results of right foot in five groups had no statistical difference (P > 0.05); 50 % PMWT results of left and right feet in three parecoxib sodium pretreatment groups were obviously higher than SNL group at different time points, which was statistically different (P < 0.05); in comparison with three pretreatment groups, the data of left foot in IT group were obviously higher than PI group and IP group, and the comparison among three groups had significant difference (P < 0.05). However, the data of right foot had no significant difference among three groups (P > 0.05). Paw thermal withdrawal latency (PTWL) results of left and right feet in five groups had no significant difference before surgery (P > 0.05); after the establishment of neuropathic model, PTWL results in five groups were significantly decreased; however, PTWL results of left and right feet at 3 days after surgery in IT group were significantly higher than the two other pretreatment groups (P < 0.05); PTWL results of left and right feet at 7 and 14 days after surgery had no significant difference. Parecoxib sodium pretreatment can effectively improve the behaviors caused by neuropathic pain, and intrathecal injection is the most effective route of administration.
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