Poster Session I

Abstract

Introduction: Peripheral neuropathy is a common adverse effect of several anti-cancer drugs, including the platinum-based drug oxaliplatin and the taxane paclitaxel. Pain and allodynia are caused by these anti-cancer drugs, but acute dysesthesia aggravated by cold is peculiar to oxaliplatin. Objectives: In the present study, we investigated whether cold allodynia would be caused by oxaliplatin and paclitaxel and whether it would be mediated by transient receptor potential melastatin 8 (TRPM8), a cation channel activated by cold temperature and cooling agents. Methods: Male C57BL/6 mice were used. Oxaliplatin (3 mg/kg) and paclitaxel (5 mg/kg) were injected intraperitoneally. For the assessment of cold allodynia, the plantar surface was stimulated with a droplet of acetone and responses to the stimulus were ranked as follows: 0, no response; 1, lifting of the hind paw; 2, flinching or licking of the hind paw. The stimulation was applied four times and the average served as response score. The expression of TRPM8 mRNA was determined by RT-PCR methods. Results: A single injection of oxaliplatin, but not paclitaxel, caused cold allodynia which peaked on day 3 and then gradually decreased by day 25. Cold allodynia was inhibited by the TRPM8 antagonist. The expression of TRPM8 mRNA was increased in the dorsal root ganglion on day 3 after the injection of oxaliplatin, but not paclitaxel. Conclusions: Acute cold dysesthesia may be caused by oxaliplatin, but not paclitaxel, in mice. It may be at least partly due to the increased expression of TRPM8 in the primary sensory neurons. MODULATION OF NEUROPATHIC PAIN IN RATS BY THE GPR55 RECEPTORJ. Ashton, P. Brownjohn. University of Otago, Dunedin, New Zealand Introduction: GPR55 is a putative third cannabinoid G-protein coupled receptor. GPR55−/− mice show altered nociceptive thresholds compared to wildtype mice in neuropathic pain models. In addition, GPR55 is expressed in activated microglia, which are known to play a key role in modulating nociceptive transmission in the dorsal horn of the spinal cord. Objectives: We therefore aimed to determine the effects of GPR55 activation with a selective ligand on nociceptive thresholds in both healthy rats and rats with neuropathic pain. We also aimed to