Adenovirus-mediated interleukin-2 gene therapy of nociception

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Abstract
The effect of adenovirus-mediated interleukin-2 (IL-2) gene on rat basal nociceptive response and chronic neuropathic pain was explored. The paw withdrawal latency induced by radiant heat was used to evaluate the antinociceptive effect of adenovirus type 5 (Ad5) and Ad5-IL-2. The results showed that intrathecal delivery of Ad5-IL-2 exhibited obvious antinociceptive effects on basal nociceptive response and chronic neuropathic pain, which were maintained for 3 and 4 weeks, respectively. This suggested that the antinociceptive effect of Ad5-IL-2 on chronic neuropathic pain was greater than its effect on basal nociceptive response. Human IL-2 mRNA was detected by in situ hybridization in the spinal pia mater and parenchyma of the lumbar, sacral, thoracic and cervical regions, and gray matter had higher level of IL-2 expression than white matter. These data demonstrated that the IL-2 gene was transfected into spinal cord regions relevant to pain modulation. The expressed IL-2 protein profile in spinal cord detected by enzyme-linked immunosorbent assay coincided almost exactly with its antinociceptive effect. This supported the hypothesis that the therapeutic effect of IL-2 gene was related to IL-2 protein expression. The study indicates that intrathecal delivery of adenovirus-mediated IL-2 gene has a relatively long antinociceptive effect.