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Abstract
Embryonic stem (ES) cells have been investigated in repair of the CNS following neuronal injury and disease; however, the efficacy of these cells in treatment of postinjury pain is far from clear. In this study, we evaluated the therapeutic potential of predifferentiated mouse ES cells to restore sensory deficits following spinal cord injury (SCI) in mice. The pain model used unilateral intraspinal injection of quisqualic acid (QUIS) into the dorsal horn between vertebral levels T13 and L1. Seven days later, 60,000 predifferentiated ES cells or media were transplanted into the site of the lesion. Histological analysis at 7, 14, and 60 days post-transplantation revealed that animals receiving ES cell transplants suffered significantly less tissue damage than animals receiving media alone. Transplanted cells provided immediate effects on both spontaneous and evoked pain behaviors. Treatment with ES cells resulted in 0% (n = 28) excessive grooming behavior versus 60% (18 of 30) in media-treated animals. In the acetone test (to assess thermal allodynia), mice recovered to preinjury levels by 12 days after ES cell transplant, whereas control animals injected with media after SCI did not show any improvement up to 60 days. Similarly, the von Frey test (to assess mechanical allodynia) and the formalin test (to assess nociceptive hyperalgesia) showed that transplantation of predifferentiated ES cells significantly reduced these pain behaviors following injury. Here we show that predifferentiated ES cells act in a neuroprotective manner and provide antinociceptive and therapeutic effects following excitotoxic SCI.
Highlights
Insult to the spinal cord initiates a devastating cascade of concomitant events that include anatomical, physiological, and neurochemical changes often leading to neuronal cell death and syrinx formation [1,2,3,4]
Animals were assessed daily for the presence of excessive grooming behavior following excitotoxic spinal cord injury (SCI)
Excessive grooming behavior is associated with the secondary injury cascade, and its onset strongly correlates to the amount of tissue damage at associated spinal segments
Summary
Insult to the spinal cord initiates a devastating cascade of concomitant events that include anatomical, physiological, and neurochemical changes often leading to neuronal cell death and syrinx formation [1,2,3,4]. Narcotic analgesics remain the most common approach in the management of moderate to severe pain [9]; adverse side effects and the potential for addiction or tolerance to pharmacological modalities have led to guarded use of these agents in pain management involving continuous long-term treatment [9,10]. These agents appear to be relatively ineffective in controlling more severe chronic pain syndromes, central pain [11].
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