Increased gene expression and production of spinal cyclooxygenase 1 and 2 during experimental osteoarthritis pain.

Abstract

Knowledge on the involvement of spinal COX-1 and COX-2 in pain due to osteoarthritis could be useful for better understanding of its pathogenesis and therapy. In this study we have investigated a long-term pattern of expression and production of spinal COX-1 and COX-2 in the model of osteoarthritis induced in rats by injection of monoiodoacetate (MIA) into the knee joint. MIA injection produced thermal hyperalgesia (assessed by the plantar test) and tactile allodynia (measured with von Frey hairs). The pain measures reached maximum on the fifht day, then remained relatively stable. The expression of spinal COX-2 mRNA reached maximum on day 5 (5.2 times; P<0.001) and remained increased until day 31 (4.9 times; P<0.001). Expression of spinal COX-1 mRNA increased gradually reaching maximum on the day 31 (4.5 times; P<0.001) when the relative expression of both genes was almost equal. The production of both proteins was almost similar at the beginning of the experiment. The highest production of COX-2 protein was observed on day 5 after the induction of osteoarthritis (increased 3.9 times). The levels of COX-1 protein increased gradually with maximum on day 31 (3.4 times). The present findings indicate that not only expression of COX-2 mRNA but also that of COX-1 mRNA is significantly increased in the spine during osteoarthritis pain. Thus, in contrast to inflammatory pain, the upregulation of spinal COX-1 may be important in osteoarthritis pain.