engleski

Local administration of therapeutic agents at the level of dorsal root ganglia - a new method to treat neuropathic pain

Introduction: After spinal nerve ligation (SNL) injury, the ionized calcium binding adaptor molecule 1 (+) (Iba-1) resident macrophages from dorsal root ganglia (DRG) become activated, cluster around large A-neurons and possibly sensitize them to induce pain. This specific arrangement of Iba (+) macrophages is associated at 5 days after injury with a significant increase of Iba-1 mRNA. The aim of this study was to test if the delivery of Iba-1 siRNA into the L5 DRG can reduce Iba-1 expression and consequently the SNL-induced pain. Materials and methods: (figure)Results. The Rat grimace scale images obtained from all experimental groups were assigned with a score of “0”, indicating the absence of pain. Behavioral tests revealed that intra ganglionic delivery of Iba-1 siRNA reduced SNL-induced mechanical allodynia and cold hyperalgesia. Western blot and PCR analysis revealed a significant inhibition of Iba-1 expression after Iba-1 siRNA injection. Electron microscopy results showed that in normal conditions, the DRG neurons were closely surrounded by satellite cells, with very few macrophages around them. After SNL, and in some part also after silencing, macrophage’s behavior is changed in 3 different unexpected ways: (1) they cluster near neurons forming a ring around them, (2) they are engulfed in the cytoplasm of neurons or (3) they can infiltrate between the satellite cells and neuronal body. Conclusions. In vivoIba-1 gene silencing with naked siRNA was highly efficient in reducing the SNL-induced pain due to a specific degradation of Iba-1 mRNA from DRG macrophages.

dorsal root ganglia ; neuropathic pain

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