Endomorphin analog exhibited superiority in alleviating neuropathic hyperalgesia via weak activation of NMDA receptors

In this study, we measured the effect of morphine and MEL‐0614 on hyperalgesia (7 days) and neuropathic allodynia (14 days) after thermal, mechanical, and cold stimulation. We fou nd that after 4 and 8 consecutive days of intrathecal administration (1, 3, and 10 nmol), morphine induced severe hyperalgesia and neuropathic allodynia, respectively. MEL‐0614 did not induce hyperalgesia at low doses (1 and 3 nmol) and had a mitigating effect on morphine‐induced neuropathic exa cerbations in spared nerve injury mice. Hyperalgesia was blocked by Dynorphin A (1—17) antibody but not by an opioid receptor antagonist. To explore the reasons for the different results of morphine and MEL‐0614, we used quantitative PCR and immunofluorescence to explore the effects of both on N MDA receptor subtype 2B (NR2B), microglia marker iba‐1, and inflammatory mediators. After 8 days of consecutive administration, morphine (10 nmol) promoted an increase in the number of NR2B, iba‐1, and inflammatory mediators in the spinal cord of mice. MEL‐0614 (10 nmol) had no significant eff ect on these factors, and after co‐administration with morphine, the expression of NR2B, iba‐1, and inflammatory mediators was lower than that with morphine injection alone. Our research showed the advantage of MEL‐0614 in terms of hyperalgesia and neuropathic allodynia, which may provide clin ical relief of hyperalgesia and neuropathic allodynia caused by morphine.
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research