Figure 11.

ErbB2 receptor inhibition or sequestration of endogenous NRG reduced mechanical pain hypersensitivity and cold allodynia after spinal nerve ligation. Animals underwent L5 SNL and received a continuous intrathecal infusion of the erbB2 inhibitor (PD168393, 1.25–10 μg/d) or vehicle for 14 d. a, Mechanical hypersensitivity developed at day 1 after SNL in both groups and after day 2 was significantly attenuated in animals receiving the erbB2 inhibitor in a dose-dependent fashion. *p < 0.05, **p < 0.001, for 10 μg/d vs vehicle; ^#p < 0.05 for 5 μg/d vs vehicle; n = 7–11/group. b, Once the pump had emptied, the withdrawal thresholds of the group receiving the erbB2 inhibitor (5 μg/d) returned to those of control. c, Delayed treatment with the erbB2 inhibitor (5 μg/d) from day 3 onward (by which time microgliosis is well established) was not effective at reversing mechanical pain-related hypersensitivity (p = 0.75) d, Cold allodynia was also significantly reduced in a dose-dependent fashion by inhibiting the erbB2 receptor. **p < 0.001 for 10 μg/d vs vehicle; ^#p < 0.05 for 5 μg/d vs vehicle, n = 7–11/group. e, f, Intrathecal administration of HBD-S-H4 (3 μg) at days 0 and 4 after SNL (shown by arrows) significantly reduced mechanical (p < 0.001) (e) and cold (p < 0.05) (f) pain-related hypersensitivity. Error bars represent ± SEM. Statistical tests: two-way ANOVA, Bonferroni test, or Fischer LSD post hoc analysis. When the assumptions of sphericity were violated (Mauchly's test; p < 0.05), the Greenhouse–Geisser correction was applied and independent two-tailed t tests were used to determine differences between groups. INH, Inhibitor (PD168393); NRG ANT, NRG antagonist (HBD-S-H4). The lines in a–d denote the period of pump infusion. The arrows in e and f denote the days of intrathecal injections.