3.7 Neuropathic Pain: MOPs in primary sensory neurons contribute to the antihyperalgesic effect of systemic opioid agonists
We sought to determine whether peripheral MOPs in primary sensory neurons mediate the analgesic effect of opioids under neuropathic pain conditions. In WT mice, s.c. injection of 5 mg∙kg-1DALDA reversed the SNIt-induced hyperalgesia, as evidenced by a significant decrease in PWF to high force mechanical stimuli from 62 ± 5.93% to 23 ± 5.17% 60 min after administration. The same dose of DALDA produced no significant analgesic effect in theOprm1 cKO group (Figure 8A) . Previous investigations have provided evidence for a peripheral component of the antinociceptive effect of systemic morphine in rodents with peripheral mononeuropathy and spinal nerve ligation-induced neuropathy (Kayser, Lee & Guilbaud, 1995; Pertovaara & Wei, 2001). In our study, s.c. injection of 5 mg∙kg-1 morphine decreased PWF from a SNIt-induced peak of 61 ± 2.77% to 18 ± 2.91% 30 min after administration (Figure 8B) . Morphine’s analgesic effect in WT mice peaked at 30 min and lasted for approximately 90 min. The same dose of morphine in Oprm1 cKO mice induced an attenuated analgesic effect. Thirty minutes after drug injection, the Oprm1cKO group exhibited a decrease in ipsilateral PWF from 61 ± 3.79% to 35 ± 5.43%. Similar to the time course in WT mice, morphine’s peak response in Oprm1 cKO mice occurred after 30 min. However, the overall effect of morphine in Oprm1 cKO mice lasted for only approximately 60 min. Notably, morphine did not induce an analgesic response in the contralateral hind paw of Oprm1 cKO mice.