Chronic pain following spinal cord injury (SCI) is estimated to occur in up to 70% of patients, with at least one-third of patients rating it as so severe that it is their primary impediment to participation in daily activities and social well-being. Neuropathic pain following SCI is particularly difficult to manage using conventional pharmacotherapies, which are modestly effective at best and may result in serious untoward side effects and misuse potential when used in the long term for chronic pain management. The persistence of pain following SCI further diminishes quality of life, impacting productivity and participation in normal daily activities, and places tremendous additional burden on families and caregivers. Thus, there is a compelling need for groundbreaking treatment options for SCI patients through the identification of new and potent therapeutic strategies.

The proposed work will explore a novel approach toward restoring quality of life in SCI patients using implantation of natural secretory cells (chromaffin cells, from the adrenal gland) that continually make analgesic molecules that can act at local spinal pain pathways to reduce pain. Chromaffin cells can be implanted within the spinal fluid via lumbar puncture without disruption of spinal neural tissue. Once implanted, the cells can act as “minipumps,” providing a local and continually renewable source of pain-relieving substances. The therapy is envisioned to require only a single one-time intrathecal injection on an out-patient basis. The proposed approach is based on a long history in our lab utilizing chromaffin cells for chronic pain alleviation in a variety of preclinical rat models. In addition, pilot clinical trials in patients with chronic pain consequent to cancer showed promising outcomes. However, at that time, feasibility for upscaling this approach was limited by the low availability of donor cells that had to be derived from donor adrenal glands, since the cells were post-mitotic and could not be expanded. With new developments in induced pluripotent stem cell (iPSC) technology, it is now possible to overcome these limitations. The iPSCs can be derived from simple tissue sources non-invasively, including the skin and blood draws and can be grown, expanded, and differentiated into specialized cell types such as the desired chromaffin cells. In addition, this can be done using a patient’s own cells, eliminating the need for immunosuppressive treatment, and could be collected and banked in freezers for future needs.

The advent of these new technologies has re-opened the possibility of developing chromaffin cell transplants for the alleviation of chronic pain. Our preliminary data using human iPSC-derived chromaffin cells reinforces the remarkable potential for sustained chronic pain treatment. Additional improvements, including 3D biomatrices and supplementary engineered analgesic peptides, will also be explored. If successful, this minimally invasive approach using readily attainable cell sources for implantation could result in alleviation of chronic SCI pain and profoundly improve quality of life. The preceding clinical experiences using this cell phenotype may provide additional supportive data toward regulatory approval as the proposed work progresses. In addition, prior preclinical work suggests that chromaffin cells are likely translatable for amelioration of other chronic pain syndromes, including traumatic peripheral neuropathic pain, neurogenic inflammation, and arthritis pain.