3.4 MOPs in primary sensory neurons are required for the antinociceptive effects of systemic DALDA and morphine
We next examined whether the absence of peripheral MOPs in primary sensory neurons affects the ability of opioids to block the response to acute nociceptive stimuli. In WT mice, the mean value for PWL to heat stimuli increased from 15.41 ± 0.62 s at baseline to 18.05 ± 0.69 s, and the mean baseline PWF to mechanical stimulation decreased from 30 ± 2.98% at baseline to 15 ± 2.69% at 60 min after s.c. injection of 5 mg∙kg-1 DALDA (Figure 5A) . In contrast, the same dose of DALDA produced no analgesic effect in the Oprm1 cKO group. In WT mice, s.c. administration of 5 mg∙kg-1morphine significantly increased PWL from 14.41 ± 1.13 s to 19.79 ± 1.28 s and significantly reduced PWF from 33 ± 2.60% to 14 ± 3.06% at 30 min post-injection (Figure 5B) . Morphine’s analgesic effect in WT mice peaked at 30 min and persisted for 60 min post-administration. However, in the Oprm1 cKO group, s.c. injection of 5 mg∙kg-1 morphine did not significantly affect the response to noxious mechanical and heat stimuli. These results suggest that peripheral MOPs in primary sensory neurons play an important role in the anti-nociceptive effect of systemically administered opioid agonists. No sex differences in the analgesic effects of DALDA or morphine were observed.