Extended Data Fig. 1: Physiological effects of VCP171 and MIPS521.

a, Chemical structure of VCP171. b, Time courses of paw withdrawal threshold (PWT) to mechanical stimulus by von Frey filaments in nerve-injured rats post-intrathecal administration of VCP171 (blue) or MIPS521 (red). Significance to vehicle control was determined using Greenhouse-Geisser correction for multiple comparisons, corrected with Dunnett’s post-hoc test, * P < 0.05, ** P < 0.01, *** P < 0.001. Data are shown as mean +/- SEM (n=8-10 rats per data group) c, Single trial place preference conditioning with intrathecal VCP171 (30 µg, blue), MIPS521 (10 µg, red) and morphine (10 µg, black) increased the time nerve-injured rats spent in the drug paired chamber, with a corresponding decrease in the vehicle paired chamber. Sham surgery rats showed no chamber preference. Empty circles show individual data points, and bars show mean +SEM (n = 8 per group). Significance was determined using a two-tailed unpaired t test assuming unequal variance, * P < 0.05, ** P < 0.01, compared to vehicle control. d, Rotarod latency in rats following intrathecal administration of VCP171 (blue) or MIPS521 (red) is not significantly different to vehicle controls, whereas intrathecal administration of morphine reduces rotarod latency to fall. Data are shown as mean +/- SEM (n = 3-4 per group). Significance was determined using a two-tailed unpaired t test assuming unequal variance, * P < 0.05, ** P < 0.01, compared to vehicle control. e, Effect of CPA (black; n = 4) or MIPS521 (solid red; n = 6) on rate of atrial contraction. Data represent mean ± SD.