• Julie Elizabeth Keeble, Jennifer Victoria Bodkin, Lihuan Liang, Rachel Wodarski, Meirion Davies, Elizabeth Soares Fernandes, Carly de Faria Coelho, Fiona Russell, Rabea Graepel, Marcelo Nicolas Muscara, Marzia Malcangio, and Susan Diana Brain.
• Pharmaceutical Science Research Division, Franklin-Wilkins Building, King's College London, Waterloo Campus, 150 Stamford Street, London SE1 9NH, UK. julie.keeble@kcl.ac.uk
• Pain. 2009 Jan 1;141(1-2):135-42.

AbstractInflammatory diseases associated with pain are often difficult to treat in the clinic due to insufficient understanding of the nociceptive pathways involved. Recently, there has been considerable interest in the role of reactive oxygen species (ROS) in inflammatory disease, but little is known of the role of hydrogen peroxide (H(2)O(2)) in hyperalgesia. In the present study, intraplantar injection of H(2)O(2)-induced a significant dose- and time-dependent mechanical and thermal hyperalgesia in the mouse hind paw, with increased c-fos activity observed in the dorsal horn of the spinal cord. H(2)O(2) also induced significant nociceptive behavior such as increased paw licking and decreased body liftings. H(2)O(2) levels were significantly raised in the carrageenan-induced hind paw inflammation model, showing that this ROS is produced endogenously in a model of inflammation. Moreover, superoxide dismutase and catalase significantly reduced carrageenan-induced mechanical and thermal hyperalgesia, providing evidence of a functionally significant endogenous role. Thermal, but not mechanical, hyperalgesia in response to H(2)O(2) (i.pl.) was longer lasting in TRPV1 wild type mice compared to TRPV1 knockouts. It is unlikely that downstream lipid peroxidation was increased by H(2)O(2). In conclusion, we demonstrate a notable effect of H(2)O(2) in mediating inflammatory hyperalgesia, thus highlighting H(2)O(2) removal as a novel therapeutic target for anti-hyperalgesic drugs in the clinic.

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