Calcitonin Gene-related Peptide Is Involved in Inflammatory Pain but Not in Postoperative Pain

Background: The aim of this study was to clarify the roles of calcitonin gene-related peptide (CGRP) in postoperative pain and inflammatory pain. Methods: CGRP knockout mice that the authors have developed and wild-type mice were used. Pain behaviors were assessed after incision and complete Freund's adjuvant (CFA) injection. Changes in CGRP and c-Fos expression in the dorsal horn were also examined. Results: Guarding pain scores in CGRP knockout mice were lower than those in wild-type mice at 24 h (3.8 1.6 vs. 6.8 +/- 1.5, P = 0.044) and 48 h (1.8 +/- 1.7 vs. 6.0 +/- 1.5, P = 0.001) after CFA injection (n = 8 to 9). Withdrawal latencies to heat stimulation in CGRP knockout mice were higher than those in wild-type mice at 24 to 72 h after CFA injection (4.9 +/- 1.0 vs. 3.4 +/- 0.8 at 24 h, P = 0.04; 5.1 +/- 0.3 vs. 3.2 +/- 0.9 at 48 h, P = 0.047; and 5.4 +/- 1.6 vs. 3.5 +/- 0.5 s at 72 h, P = 0.045) (n = 11 to 13), but withdrawal thresholds to mechanical stimulation were comparable. CGRP expression was increased at 24 h after CFA injection in wild-type mice, and the c-Fos-positive profile was increased at 4 h after CFA injection (ipsilateral vs. contralateral: 12.3 +/- 4.6 vs. 1.3 +/- 1.9, P < 0.0001) and maintained at 24 h (10.0 +/- 4.1 vs. 0.8 +/- 1.3, P < 0.0001) (n = 4 to 6). Conclusion: These results suggest that contribution of the CGRP system depends on the modality of pain and the stage of inflammation.