The effect of perineural colchicine on nerve injury-induced spinal glial activation and neuropathic pain behavior

Factors transported centrally from the site of a peripheral nerve injury ar e known to provide cellular activation signals to the dorsal root ganglion and spinal cord. Yamamoto and Yaksh [35] were able to use colchicine disrup tion of axonal transport to abolish thermal hyperalgesia after sciatic chro nic constriction in the rat. The current study set out to ascertain whether this observation could be reproduced by applying the same pharmacologic pa radigm to a complete, segmentally specific, spinal nerve tight ligation (SP TL) and assessing the impact of this treatment on mechanical allodynia and central, spinal glial activation. Mechanical allodynia of the ipsilateral ( lesion side) hind paw was measured at 1, 3, 5, 7, 10, and 14 days following SPTL, Spinal astrocytic and microglial activation were assessed immunohist ochemically at 5 and 14 days. Colchicine was unable to prevent mechanical a llodynia or spinal glial activation when applied perineurally just proximal to the site of SPTL, Administered alone, colchicine (without SPTL) induced both astrocytic and microglial activation, but not mechanical allodynia. C olchicine applied distal to the site of SPTL did not alter mechanical allod ynia or glial responses to SPTL. Neuronal tracing experiments were performe d to verify segmental disruption of axonal transport by either SPTL or colc hicine treatment. Neuronal tracer injected into the sciatic nerve could not be found at the L-5 spinal level following perineural colchicine treatment or tight ligation of the L-5 spinal nerve, however, tracer was present at the unobstructed L-4 spinal level. These results suggest that central astro cytic and microglial responses may be triggered by disruption of transporte d signals from the periphery, because they are induced by either colchicine or tight ligation. Conversely, axonally transported factors, either from t he site of nerve injury or from the periphery, do not appear to be critical for the development of mechanical allodynia. (C) 1999 Elsevier Science Inc .