Acta Academiae Medicinae Sinica

Abstract: Objective To examine the analgesic effect of calpain inhibitor ALLN on the zymosan-induced paw inflammatory pain and its effect on the expression of cyclooxygenase-2 (COX-2) in the spinal dorsal horn. Methods Forty-eight Sprague-Dawley rats were equally divided into three groups: control group, sham-operated group, and zymosan group. According to Meller's method, zymosan (1.25 mg) was injected intraplantarly to induce paw inflammation in zymosan group; an equal volume of PBS was administered in the sham-operated group. Mechanical withdrawal threshold (MWT) and maximum thickness of paw were tested or measured before and 0.5, 1, 2, 4, 8, and 24 hours after injection. All rats were killed at different occasions following surgery to examine calpain activity in the spinal dorsal horn with Western blot analysis. Another sixty-four Sprague-Dawley rats were divided into three groups: sham-operated group, zymosan-induced paw inflammation with intraperitoneal dimethyl sulphoxide (DMSO) treatment group, and zymosan-induced paw inflammation with intraperitoneal calpain inhibitor ALLN treatment group. MWT and maximum thickness of paw were tested or measured before and 0.5, 1, 2, 4, 8, and 24 hours after injection. All rats were killed at different occasions following surgery to examine the COX-2 expression in the spinal dorsal horn with Western blot analysis. Results MWT significantly decreased in the rats with zymosan-induced paw inflammation, while the maximum thickness of paw significantly increased, compared with control and sham-operated rats (P<0.05. Calpain in the ipsilateral spinal dorsal horn was dramatically activated after zymosan injection (P<0.01). Intraperitoneal ALLN injection significantly increased zymosan-induced MWT and decreased paw edema at the same time points after zymosan injection compared with DMSO treatment group (P<0.05). Meanwhile, calpain inhibitor ALLN treatment significantly decreased the COX-2 expression in the spinal dorsal horn compared with DMSO treatment (P<0.01).Conclusion Administration of calpain inhibitor ALLN is effective to attenuate zymosan-induced paw inflammatory pain. Calpain activation may be one aspect of the signaling cascade that increases the COX-2 expression in the spinal cord and contributes to mechanical hyperalgesia after peripheral inflammatory injury.

Key words: zymosan, inflammatory pain, cyclooxygenase-2, dorsal horn, calpain, inhibitor