Short communicationRole of vanilloid VR1 receptor in thermal allodynia and hyperalgesia in diabetic mice
Introduction
Behavioral reactions of hyperalgesia in animal models of diabetes have been described previously Calcutt and Chaplan, 1997, Kamei et al., 1991, Ohsawa and Kamei, 1999a. We recently reported that the heat intensity at a bulb voltage of 35 V, which did not produce a tail-flick response in non-diabetic mice, produced a tail-flick response in diabetic mice Ohsawa and Kamei, 1999a, Ohsawa and Kamei, 1999b. Furthermore, the tail-flick latency after heating the tail at 50 V in diabetic mice was significantly shorter than that in non-diabetic mice Ohsawa and Kamei, 1999a, Ohsawa and Kamei, 1999b. However, there were no significant differences in the tail-flick latencies between diabetic and non-diabetic mice after heating the tail at 25, 65 and 80 V Ohsawa and Kamei, 1999a, Ohsawa and Kamei, 1999b. Based on these results, we proposed that diabetic mice exhibit thermal allodynia and hyperalgesia in the tail-flick test Ohsawa and Kamei, 1999a, Ohsawa and Kamei, 1999b. Furthermore, we also suggested that the thermal allodynia and hyperalgesia in diabetic mice may be due to the hyperactivity of C-fiber in the spinal cord, since pretreatment with capsaicin 24 h before testing reverses thermal allodynia and hyperalgesia in diabetic mice (Ohsawa and Kamei, 1999a). The vanilloid VR1 receptor is a ligand-gated, non-selective cation channel that is expressed predominantly by sensory neurons, probably in unmyelinated C-fibers Caterina et al., 1997, Caterina et al., 1999, Helliwell et al., 1998, Tominaga et al., 1998. Vanilloid VR1 receptor can also be activated by capsaicin, noxious heat (>43°C) and extracellular acidification (pH<6) Caterina et al., 1997, Tominaga et al., 1998, which excite nociceptors and evoke pain in humans or pain-related behaviors in animals De Castro et al., 1998, Garcia-Hirschfeld et al., 1995, Steen et al., 1992. Thus, these results raise the possibility that vanilloid VR1 receptor might be involved in the mechanisms of thermal allodynia and hyperalgesia in diabetic mice. Therefore, in the present study, we examined the role of vanilloid VR1 receptor in the thermal allodynia and hyperalgesia in diabetic mice using anti-vanilloid VR1 receptor serum.
Section snippets
Animals
Male ICR mice (Tokyo Laboratory Animals Science, Tokyo, Japan), weighing about 20 g at the beginning of the experiments, were used. They had free access to food and water in an animal room which was maintained at 24±1°C with a 12-h light–dark cycle. Animals were rendered diabetic by an injection of streptozotocin (200 mg/kg, i.v.) prepared in 0.1 N citrate buffer at pH 4.5. Age-matched non-diabetic mice were injected with vehicle alone. The experiments were conducted 2 weeks after the injection
Results
As shown in Fig. 1, in non-diabetic mice, a bulb voltage of 35 V did not cause a tail-flick response within the 30-s limit. However, when the voltage of the bulb was increased to 50 V, the mean tail-flick latency was significantly less than 30 s (Fig. 2). On the other hand, the heat intensity at a bulb voltage of 35 V did evoke a tail-flick response in diabetic mice, indicating that diabetic mice exhibit thermal allodynia (Fig. 1). Furthermore, the tail-flick latency at a bulb voltage of 50 V
Discussion
In the present study, diabetic mice showed thermal allodynia and hyperalgesia in the tail-flick test. These results are consistent with our previous observations that streptozotocin-induced diabetic mice showed thermal allodynia and hyperalgesia in the tail-flick test Ohsawa and Kamei, 1999a, Ohsawa and Kamei, 1999b, Kamei and Zushida, 2000.
In the present study, we observed that i.t. pretreatment with an anti-vanilloid VR1 receptor serum at 1:3000 produced significant antinociception in the
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