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Lipo-Endomorphin-1 Derivatives with Systemic Activity against Neuropathic Pain without Producing Constipation

Figure 4

Intravenous dosing of compounds 3 and 4 in the ipsilateral hindpaw of CCI-rats.

Paw withdrawal threshold (PWT) versus time curves for single bolus i.v. doses of compounds A) 3; B) 4, and vehicle in CCI-rats; C) The extent and duration of antinociception (areas under the ΔPWT versus time curves, ΔPWT AUC values) produced by single i.v. bolus doses of compounds 3 and 4 at 0.8 and 0.5 µmol/kg, respectively, was significantly greater than that produced by vehicle. This effect was comparable with the effect of morphine at 2 µmol/kg. Each value represents mean (± SEM). **p<0.01, ***p<0.001 compounds 3 and 4 vs. vehicle treated CCI-rats (n = 6–8).

Figure 4

doi: https://doi.org/10.1371/journal.pone.0041909.g004