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. Author manuscript; available in PMC: 2014 Nov 1.
Published in final edited form as: Pain. 2013 Jul 20;154(11):10.1016/j.pain.2013.07.023. doi: 10.1016/j.pain.2013.07.023

Fig. 4.

Fig. 4

Pretreatment with locally administered naloxone methiodide and MK-801 did not prevent the development of tolerance to intraplantar loperamide. Intraplantar injection of loperamide (150 µg/50 µL) significantly increased the ipsilateral paw withdrawal threshold (PWT) of spinal nerve ligation (SNL) rats (i.e., reversed mechanical allodynia) under pretolerance conditions. During induction of tolerance, rats were administered an intraplantar injection of MK-801 (10 µg/20 µL, n = 6), naloxone methiodide (100 µg/20 µL, n = 6), or saline (n = 4) 10 minutes before each injection of loperamide (300 µg/30 µL intraplantarly). After tolerance induction, the inhibitory effect of local loperamide (150 µg/50 µL intraplantarly) diminished in all 3 groups. However, systemic loperamide (1.5 mg/kg subcutaneously) significantly increased the PWT in local loperamide-tolerant animals. Data are expressed as mean ± SEM. **P < .01, ***P < .001 versus preinjection PWT.