Neuropathic pain after spinal cord injury (SCI) significantly impairs quality of life and current treatments provide insufficient relief. Although neuropathic pain is incompletely understood, the inhibitory neurotransmitter GABA becomes deficient after SCI. Without descending or local inhibition, excitatory pathways predominate, leading to hypersensitivity and neuropathic pain.

We have subcloned a human neuronal cell line, hNT2.17, which secretes inhibitory neurotransmitters after differentiation of the cells into a mature neuronal phenotype. In a rat model of excitotoxic spinal cord injury (QUIS), subarachnoid transplantation of this cell line results in recovery from behavioral hypersensitivity induced by the injury.

Male Wistar-Furth rats (n=12/group: Naïve; QUIS-alone; QUIS+Viable cell transplant and QUIS+Non-viable cell transplant) underwent QUIS injury followed by intrathecal transplantation of viable and non-viable cells (2 weeks after QUIS) at the optimal dose of 10⁶ cells/graft. Behavioral testing (mechanical allodynia and thermal hyperalgesia) was performed for 8 weeks. Varying durations of cyclosporine (100mg/kg i.p.) (1 day, 1 week or 2 weeks) were examined to determine the minimal necessary immunosuppression (n=8/group).

Animals undergoing viable hNT2.17 cell transplantation demonstrated complete reversal of all hypersensitivity (p<0.001). Minimal immunosuppression (1 day) resulted in only temporary recovery of hypersensitivity, after which values returned to those of injured animals. One week of immunosuppression resulted in sustained recovery of cutaneous allodynia but not of thermal hyperalgesia. Two full weeks of immunosuppression caused statistically significant and durable recovery of all behavioral hypersensitivity. Immunohistochemistry confirmed that grafted cells were present and synthesizing GABA at the end of the experiment.

Differentiated human NT2.17 cells are mature inhibitory neurons that can be used as biologic minipumps to successfully treat neuropathic pain of SCI origin. Intrathecal transplantation requires at least 2 weeks of immunosuppression to maintain durable effect of the grafted cells.