BACKGROUND: We designed this study to evaluate the antinociceptive effect and changes in amounts of substance P in the spinal cord after perineural application of capsaicin to the injured nerve in rats in neuropathic pain. METHODS: Male Sprague-Dawley rats (200-250 g) were prepared with the tight ligation of the left L5, 6 spinal nerves or with the sham operation. They were divided into 3 groups according to the solution treated to the left sciatic nerve and pre-treated condition, group I (capsaicin treatment after ligation; n = 10), group II (solvent treatment after ligation; n = 10), group III (capsaicin treatment after sham operation; n = 10). The withdrawal threshold to touch with von Frey filaments and the withdrawal time to thermal stimulus by plantar tester were measured and percent maximum possible effects (%MPE) were calculated, respectively, at 1, 2, 3 and 4 weeks after treatment. The area and integrity optical density (IOP) of substance P stained immunohistochemically in the lumbar dorsal horn were quantified with an image analyzer in group I. RESULTS: In the capsaicin-treated groups (I, III), withdrawal time to thermal stimulus was prolonged significantly during the 4 weeks as compared with baseline values before treatment (P < 0.05), but withdrawal time to touch didn't change. The %MPE of capsaicin to thermal stimulus in group I was significantly higher than that in group III (P < 0.05). In group II, withdrawal responses to touch and thermal stimulus didn't change. The area and IOP of substance P in the left lumbar dorsal horn at the 1st and 4th week didn't change, compared with the baseline before capsaicin treatment, except for theIOP at the 4th week in group I. CONCLUSIONS: Perineural application of capsaicin to the injured nerve in neuropathic rats does not inhibit hypersensitivity to touch but inhibit reaction to thermal stimulus. Its effect does not depend on the changes in amounts of substance P in the ipsilateral lumbar dorsal horn.