THIS study provides direct evidence from measurements of its metabolites, NO2−and NO3−, that NO is released in the spinal cord during central sensitization. A micro-dialysis fiber was implanted in the dorsal horn at L5 for collecting dialysate and administering drugs. Dialysate was pumped through a cadminum reducing column, a post-column derivatizing unit, and then a u.v. detector. After injection of capsaicin into one hind foot, NO2−increased in the dialysate. Pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) significantly reduced NO release induced by a second injection of capsaicin into the opposite foot. This supports the ideas that NO is involved in central sensitization in the spinal cord and contributes to hyperalgesia and allodynia following capsaicin injection.