Fig. 4. Experimental design for algesimetry.

The antinociceptive effect of NPs was tested in a pathophysiological context induced by an intraplantar carrageenan injection (2% saline, 100 μl). Involvement of central or peripheral opioid receptors was performed using a brain-permeant opioid antagonist, naloxone (Nal), and a brain-impermeant opioid receptor antagonist, naloxone methiodide (Nal-M). NP suspensions or control solutions were injected intravenously with a dose volume of 10 ml/kg during 30 s. The Hargreaves test was performed 10 min after the NP administration and then every 30 min up to a period of 250 min. The dose of LENK-SQ NPs (20 mg/kg) was equivalent to LENK (11.48 mg/kg) and to SQ NPs (8.28 mg/kg) and corresponded to 20.66 mmol/kg for both LENK-SQ and LENK. s.c., subcutaneous; i.pl., intraplantar.