Colchicine treatment of the sciatic nerve reduces neurogenic extravasation, but does not affect nociceptive thresholds or collateral sprouting in neuropathic or normal rats

Abstract

The effect of topical colchicine treatment of the sciatic nerve on sciatic and saphenous nociceptive thresholds and neurogenic extravasation was investigated in normal and neuropathic rats. After a pilot investigation using several different concentrations of colchicine it was determined that treating the sciatic nerve with 5 mM colchicine did not usually affect the heat nociceptive threshold over the sciatic innervated plantar surface of the hindpaw. Mechanical nociception and motor function were also unchanged. Electrical stimulation of the sciatic nerve after intravenous injection of Evans blue dye causes extravasation of the dye in the cutaneous distribution of the nerve. The area and quantity of sciatic extravasation were measured 3 weeks after treating the sciatic nerve with colchicine. This treatment results in a marked loss of neurogenic extravasation, but there were no changes in the sciatic and saphenous mediated heat and mechanical nociceptive thresholds. The area of saphenous nociceptive innervation was mapped using pinch responses and saphenous neurogenic extravasation acutely after sciatic section. There was no change in the cutaneous distribution of saphenous nociceptive fibers when measured 3 weeks after the sciatic colchicine treatment. Some rats had their sciatic nerves transected immediately after colchicine treatment (5 and 50 mM) and the saphenous nociceptive thresholds and autotomy scores were followed postoperatively. Colchicine pretreatment of the sciatic nerve has no effect on the development of hyperalgesia or autotomy. Colchicine blocks axonal transport in peripheral nerve, including the orthograde transport of tachykinins, which probably explains its ability to induce prolonged reductions in sciatic neurogenic extravasation at concentrations that spare C-fiber nociceptor function. Sciatic nerve colchicine treatment does not trigger nociceptive fiber collateral sprouting from the adjacent saphenous nerve, nor does it influence the development of hyperalgesia and autotomy behavior after sciatic transection.