[Abstract Title]. - Society for Neuroscience

and dose-response curves were plotted to detect the antinociceptive efficacies. RO extract like
either TR or AA, produced a significant (P < 0.001) dose-dependent antinociceptive response in
rats (RO: ED50 = 222.8 mg/kg versus TR: ED50 = 11.1 mg/kg and AA: ED50 = 206.1 mg/kg).
Nevertheless, nociception produced by RO extract in the PIFIR model was not modified in
presence of naloxone but the antinociceptive effect was reverted in presence of WAY 100635 (P
< 0.05). These results suggest that 5-HT1A receptors are involved in the antinociceptive effect of
RO extract determined in the PIFIR model. These results strongly suggest that aerial parts of RO
possess antinociceptive activity, and reinforce the use of this plant in folk medicine. In addition,
the specific mechanism of action of RO extract is unknown, but this study suggests that 5-HT1A
receptors are involved in its antinociceptive effect.
Disclosures: A.L. Martinez-Martinez, None; M.E. Gonzalez-Trujano, None; F.J. Lopez-
Munoz, None.
Poster
270. Pain: Opioids and Other Analgesics II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 270.16/HH15
Topic: D.08.r. Opioids and other analgesics
Support: Adolor Corporation
Title: Multifaceted evaluation of opioid-induced microglial responsiveness
Authors: P. E. STEVIS, M. S. FESCHENKO, H. GUAN, S. W. POSER, *R. T. WINDH;
Cell and Mol. Signaling, Adolor Corp, Exton, PA
Abstract: The involvement of glia in the initiation and maintenance of chronic pain states is
becoming an established premise, fueling intense research efforts aimed at decoding the
underlying mechanisms. Of particular interest is the possibility that drugs used clinically to treat
pain may promote glial activation, potentially limiting their analgesic efficacy. For example, mu
opioid receptor (MOR) agonists such as morphine are reported to activate microglia and
astrocytes, whereas opioid receptor antagonists such as naloxone inhibit glial activation by LPS.
However, the mechanisms of these actions have not been conclusively identified, and effective
concentrations of MOR ligands in these assays are often several orders of magnitude above the
affinity for MOR. To evaluate the direct effects of MOR ligands on microglial activity and
explore potential mechanisms, the murine microglial cell line, BV-2, was treated with MOR
agonists and antagonists. Kinase activation (extracellular signal-regulated kinase (ERK) and p38
phosphorylation), transcriptional regulation (NF-θB reporter gene activity) and release of factors