Loose ligatures placed unilaterally on the sciatic nerve results in a thermal hyperalgesia. We applied 5 or 50 mM colchicine (COL, blocker of the fast axonal transport) to the sciatic nerve and examined the effects of COL on thermal hyperalgesia and the levels of substance P (sP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) in the spinal cord and the sciatic nerve. These data showed that the application of 50 mM COL to the sciatic nerve in this study functioned as an axonal transport blocker. COL abolished the hyperalgesic state in a concentration-dependent manner when applied proximal to the constriction injury. COL (50 mM), when applied distal to the injury, had no effect on the hyperalgesia. COL did not alter motor function or paw withdrawal response in the non-lesioned animal. Examination of peptide levels in nerve shows that COL resulted in an accumulation of sP, CGRP and VIP in the nerve. In the dorsal horn, COL resulted in a modest reduction in levels of sP and CGRP as compared to the non-lesioned side while VIP levels were elevated. These data suggest that active factors generated by the focal nerve compression and carried by fast axonal transport from the lesioned site to the spinal cord and/or dorsal ganglion are important in the development of thermal hyperalgesia after constriction injury in rats.