Effects of sex, hindpaw injection site and stimulus modality on nociceptive sensitivity in arthritic rats

Injection of Complete Freund's adjuvant (CFA) into the hindpaw produces inflammation and alterations in nociceptive sensitivity. The present study was designed to compare the effects of CFA injection into the dorsal and plantar surfaces of the hindpaw on nociceptive sensitivity of the hindpaw to mechanical pressure, warm-water and a hotplate stimulus in male and female rats. CFA or vehicle (VEH) was injected into the dorsal or plantar surface of the right hindpaw on day 0 and tests were conducted on days 4, 6, 8, 10, 11 and 18. Up until day 11 the inflammation was confined to the injected hindpaw (monoarthritic state), whereas by day 18 both hindpaws were inflamed (polyarthritic state). The site of the CFA injection had minimal effects on thermal or mechanical sensitivity with the following exceptions. On days 11 and 18 males had higher hotplate latencies when injected in the dorsal as compared to the plantar surface. For both males and females, warm-water paw withdrawal latencies were longer in those rats injected in the dorsal versus the plantar surface on day 18. No sex differences in paw pressure thresholds were observed on days 11 and 18 in CFA-treated rats. In the warm-water paw withdrawal test CFA-treated males exhibited longer latencies than CFA-treated females on day 11, but similar latencies on day 18. In the hotplate test CFA-treated females exhibited shorter latencies than CFA-treated males on days 11 and 18. The present results demonstrate that nociceptive sensitivity is the result of the interplay among sex, CFA injection site (plantar vs. dorsal), arthritic state (mono- vs. polyarthritic) and stimulus modality (mechanical vs. thermal).