Mast cell stabilization promotes antinociceptive effects in a mouse model of postoperative pain

Makoto Yasuda, Kanta Kido, Norimasa Ohtani, Eiji Masaki

Department of Dental Anesthesiology and Pain Management, Tohoku University Hospital, Sendai, Japan

Background: Nerve injury and consequent inflammatory responses produced by surgical incision result in a complicated pain status which still affects half of all surgical patients. Therefore, it is essential for anesthesiologists to identify the mechanisms of postoperative pain. Mast cells are resident cells of connective tissue and the mucosa that participate in the immune response. Degranulation of mast cells is involved in the development of postoperative pain and can be induced by surgical incision. The aim of this study was to investigate whether stabilization of mast cells causes an antinociceptive effect in a mouse model of postoperative pain.
Methods: Postoperative pain was induced by making an incision in the hind paw of BALB/c mice. The mast cell membrane stabilizer cromoglycate (200 µg/20 µL) was injected before incision of the paw, and postoperative pain responses were measured by assessing guarding behavior, withdrawal threshold to mechanical stimuli, and latency of heat pain behavior 1, 2, and 7 days after the incision.
Results: The incision produced guarding pain, mechanical allodynia, and heat hypersensitivity. Cromoglycate decreased the guarding pain score (day 1) and the withdrawal threshold to mechanical stimuli (days 1, 2, and 7). However, the withdrawal latency to heat was not affected by cromoglycate treatment.
Conclusion: Cromoglycate significantly attenuated the pain response expressed as guarding pain and mechanical allodynia in a mouse model of postoperative pain. Thus, mast cell activation is likely a mechanism of postoperative pain and is an interesting target for the development of new therapies.

Keywords: postoperative pain, mast cells, cromoglycate