Mast cell mediators are sufficient to induce persistent nociception and long-term potentiation. Intrathecally injected supernatant from cultured mast cells activated for 1 hour induces significant mechanical hyperalgesia at 1 day post injection, while supernatant from mast cells activated for 24 hours induces significant mechanical hyperalgesia at 4 hours, 1 day, 2 days, and 4 days post-injection (* = P < 0.05) (A). No significant thermal hyperalgesia is seen (B), although cold allodynia is detected at 4 hours and 1 day post injection of supernatant from mast cells activated for both 1 hour and 24 hours (* = P < 0.05) (C). TNFα, IL-6, and IL-4 are detected in supernatant from 24 hour activated mast cells, and a lower level of IL-6 is detected in supernatant from 1 hour activated mast cells (BD: below detection). Experiment is representative from mast cell supernatant obtained from two independent batches of mast cells that were subsequently used in behavioral and electrophysiology experiments (D). LTP is elicited in 4 out of 6 animals from lumbar spinal application of supernatant of 1-hour stimulated mast cells (E), and in 6 out of 6 animals from lumbar spinal application of supernatant of 24-hour stimulated mast cells (F) (Calibration bars: 100 ms, 0.2 mV).