The differential effects of acetaminophen on lipopolysaccharide induced hyperalgesia in various mouse pain models

We investigated effects of acetaminophen on LPS-induced hyperalgesia in various pain models. We examined the changes of pain behaviors induced by formalin injected subcutaneously (s.c.) in the hind paw, with substance P (SP) and glutamate injected inthrathecally (i.t.). Hyperalgesia was induced by LPS intraperitoneal injection 1 day prior to the pain test. LPS-induced hyperalgesia was exhibited in nociceptive behaviors induced by formalin s.c. (only in the second phase), SP and glutamate i.t. injection. APAP showed a dose-dependent antinociceptive effect on the saline- and LPS-pretreated group in the formalin and SP pain model. However, the analgesic effect of APAP was not observed in the glutamate pain model. To clarify the action site, APAP was administered i.t. or intracerebroventricularly (i.c.v.) 30 min prior to behavioral tests. The 2nd phase of formalin response was not only increased by LPS, but it also significantly attenuated by i.c.v. injections of APAP. However, the effect of APAP was observed only in the LPS-pretreatment, but not in the control group. These results suggest that LPS-induced hyperalgesia in the formalin 2nd phase may be involved in the SP-sensitive neuronal pathways, in which the hyperalgesic response elicited by LPS attenuated by APAP with supraspinal pain modulatory mechanisms.