Figure 2.
EP1, EP2, and EP4 receptor agonists (ONO-DI-004, butaprost, ONO-AE1 329) induce spinal hyperexcitability. A, Columns show the average increase (mean ± SEM) of the responses of neurons during innocuous (innoc.) and noxious (nox.) pressure onto the knee joint during the last 25 min under different concentrations of the agonists. The baseline (B) (absolute values, see below) was set to zero. Asterisks show the lowest concentration of the agonist that caused a significant increase in the response to mechanical stimulation compared with the baseline. B, Curves show the time course of the facilitation of the responses to noxious and innocuous pressure applied to the knee joint and to the ankle. The values after drug applications show dose-dependent increases (mean ± SEM) of the responses over B (set to zero) (n = number of neurons). Because not all neurons with responses to knee stimulation showed responses to ankle stimulation, n was lower for ankle stimulation in some cases. The predrug baseline values were as follows (measured as impulses per 15 sec; mean ± SEM) : innocuous pressure knee joint, 46 ± 21 (EP1), 19 ± 11 (EP2), 16 ± 11 (EP4); noxious pressure knee joint, 153 ± 36 (EP1), 243 ± 98 (EP2), 183 ± 76 (EP4); innocuous pressure ankle, 32 ± 17 (EP1), 3 ± 2 (EP2), 19 ± 8 (EP4); noxious pressure ankle, 152 ± 60 (EP1), 94 ± 40 (EP2), 169 ± 109 (EP4).