Hyperalgesia to Cold in Persistently Inflamed Rats: Changes in C-Fiber-Receptor Activities and Cold-Sensitive Ion Channel Expression

摘要

In chronic inflammatory conditions such as rheumatoid arthritis, exposure to a cold environment often induces pain that interferes with patients' everyday lives (Jahanshahi et al. 1989; Jamison et al. 1995; Drane et al. 1997). Many complain that their pain worsens even with mild temperature decreases that are surely not noxious. In animal models of persistent inflammation, hyperalgesia to noxious cold (<10degC) appears in rats about 1 week after induction of inflammation (Perrot et al. 1993; Jasmin et al. 1998), at which time hyperalgesia to heat disappears (Hylden et al. 1989). However, few studies have investigated the effects of mild cold on pain (Sato et al. 2000). In addition, research on cold hyperalgesia has focused on its central mechanism in neuropathic pain conditions; virtually no research has looked at peripheral mechanisms. This situation contrasts sharply with the many studies on the peripheral mechanisms of mechanical or heat hyperalgesia in inflammation (Kocher et al. 1987; Schaible and Schmidt 1988; Mizumura and Kumazawa 1996; Andrew and Greenspan 1999; Koltzenburg et al. 1999; see Mizumura 1998 for review). We thus "wanted to clarify the altered sensitivity to cold of C-fiber sensory receptors in a condition of persistent inflammation. We found that inflammation enhances the response to cold of C-fiber low-threshold mechanoreceptors and increases the percentage of nociceptors sensitive to cold (Takahashi et al. 2003).