Peripheral Formalin Injection Induces Long-Lasting Increases in Cyclooxygenase 1 Expression by Microglia in the Spinal Cord

Abstract

Activated glia are a source of substances known to enhance pain, including centrally synthesized prostaglandins. We have previously shown that microglia are activated in the spinal cord following peripheral formalin injection. In the present study, we investigated cyclooxygenase (COX-1 and COX-2) expression in the spinal cord using immunohistochemistry and Western blots in the formalin pain model, to further understand how spinal glia modulate pain processing. We show that both COX-1 and COX-2 are constitutively expressed in the spinal cord. Hind paw formalin injection increased COX-1 expression, beginning at 1 day after injection and lasting at least 2 weeks, the duration of experiments. The COX-2 expression changed considerably less, with a significant increase of COX-2 protein level only observed at 2 h after injection. Double labeling studies showed that COX-1 was expressed in microglia and COX-2 was expressed in neurons. These data indicate that both COX-1 and COX-2 are increased in the spinal cord following formalin injection, but the time course and cellular sources are different, suggesting that both COX-1 (longer time points) and COX-2 (very short time points) may be involved in spinal modulation in the formalin pain model. Our study also suggests that spinal microglial activation may play a role in long-term hyperalgesia through the increased expression of COX-1. Perspective This article reports that COX-1 expression by microglia is increased in the spinal cord after peripheral formalin injection into the rat hind paw. This result could potentially help clinicians understand how COX-1 may be involved in pain processing and the role microglial activation plays in pain mechanisms.