Following a peripheral nerve lesion, regenerating afferent A- and C-fibers may generate ectopically ongoing activity and activity evoked by mechanical, heat or cold stimuli. Here we investigate the effect of inflammatory mediators on these ectopic activities. Using in vivo electrophysiology, regenerating afferent nerve fibers were investigated 7-14 days after sural nerve crush lesion. The characteristics of ectopic activity were determined before and up to 1.5 hours after topical application to the nerve of a mixture of inflammatory mediators (Inflammatory Soup, IS). A total of 73 C-fibers and 22 A-fibers that were ectopically active before application of IS (61 C-fibers, 17 A-fibers) or recruited by IS (12 C-fibers, 5 A-fibers) were investigated. In more than half of the C-fibers the ongoing activity was increased or appeared de novo during application of IS and remained significantly elevated for up to 90 minutes after its removal. The majority of mechano- (23/38) and heat-sensitive (29/35) C-fibers as well as mechano-sensitive A-fibers (12/17) decreased their activation thresholds and/or increased the response magnitude to mechanical and/or heat stimulation of the nerve. Noxious cold sensitivity, but not non-noxious cold sensitivity, was weakly influenced by IS. Some initially non-responsive C- and A-fibers developed new ectopic properties, i.e. were recruited, and exhibited ongoing activity and/or could be activated by physiological stimuli after application of IS. The results suggest that inflammatory mediators may be critical to generate and enhance ectopic excitability of regenerating afferent nerve fibers. These peripheral mechanisms may be important triggering and maintaining neuropathic pain.