Previous studies have shown that peripheral administration of the TRPV1 antagonist, capsazepine reduces thermal hyperalgesia in a carrageenan model of inflammatory pain (Kwak et al., 1998; Menendez et al., 2004) . The aim of the present study was to evaluate the role of peripheral TRPV1 receptors in mediating thermal hypersensitivity of spinal neurones in the carrageenan model of inflammation. Here, we have determined the effects of peripheral administration of the potent TRPV1 receptor antagonist, iodoresiniferatoxin (IRTX, 0.005 and 0.5 nmol/rat) on noxious heat (45 °C)-evoked responses of dorsal horn wide dynamic range neurones (WDR) in naïve and carrageenan-inflamed in rats.

Ex tracellular single-unit recordings of deep (500-1000 µm) WDR neurones were made in isoflurane anaesthetised naïve and carrageenan-inflamed male Sprague-Dawley rats (225-275 g). 45 °C thermal stimuli were applied for 10 s at 10 min intervals to the peripheral receptive field and evoked responses (spikes/s) of WDR neurones were recorded. Effects of intraplantar injection of IRTX (0.005 and 0.5 nmol in 50 µl)) or vehicle (ethanol: Tween 80: saline, 1: 3: 96) on 45 °C-evoked responses were studied. Effects of intraplantar injection of carrageenan (2 mg/rat) or saline on 45 °C-evoked responses of WDR neurones were measured for 180 min post-injection. In a group of carrageenan-inflamed rats, effects of intraplantar injection of IRTX (0.005 and 0.5 nmol) or vehicle (at 130 min post-carrageenan injection) on 45 °C evoked responses of WDR neurones were studied. Data were analysed using a Mann-Whitney non-parametric test.

Control 45 °C-evoked responses of WDR neurones did not differ between treatment groups. Intraplantar injection of IRTX (0.5 nmol) in naïve rats significantly reduced 45 °C-evoked responses of WDR neurones (mean ± SEM, 44 ± 9 % of control, P = 0.002, n = 6) and the lower dose (0.005 nmol, n = 4) had no effect, compared to vehicle (n = 6). Intraplantar injection of carrageenan produced a significant increase in 45 °C-evoked responses of WDR neurones (mean ± SEM, 162 ± 26 % of control, P = 0.045, n = 8), compared to saline (n = 5). Intraplantar injection of vehicle produced a non-significant reduction in responses of WDR neurones in carrageenan-treated rats. Intraplantar injection of both the doses of IRTX in carrageenan-inflamed rats significantly reduced 45 °C-evoked responses of WDR neurones (mean ± SEM: IRTX (0.005 nmol), 47 ± 9 % of control, P = 0.001, n = 6; IRTX (0.5 nmol), 50 ± 14 % of control, P = 0.004, n = 7) , compared to vehicle (n = 7).

These data support the role of peripheral TRPV1 receptors in noxious thermal transmission in naïve and inflamed rats. The inhibitory effect of lower dose (0.005 nmol) of IRTX on thermally-evoked responses in carrageenan-inflamed rats, but not in naïve rats, suggests sensitisation of TRPV1 receptors in acute inflammatory conditions.

Kwak et al. (1998). Neuroscience 86, 619-26.
Menendez et al. (2004). Life Sci 74, 3235-44.