Male Sprague Dawley rats received bilateral microinjections of saline or of saporin, dermorphin, or the dermorphin–saporin conjugate (Derm/Sap) (1.5 pmol on each side of the RVM). After 28 d, the rats were subjected to either L5/L6 SNL or sham surgery.Vertical dashed lines represent time of surgery. Paw-withdrawal thresholds to light tactile stimuli (A) and to noxious radiant heat (B) were determined before microinjections (BL), weekly after the microinjections, and daily for 14 d after SNL or sham surgery. Tactile hypersensitivity (A) and thermal hyperalgesia (B) were evident in all groups with SNL during the initial 4 d of testing, as indicated by the significant decreases in response thresholds. However, the rats pretreated with the dermorphin–saporin conjugate demonstrated clear reversal of SNL-induced threshold changes commencing at postsurgery day 5. *p ≤ 0.05 compared with premicroinjection values.