Endomorphin-1 and endomorphin-2 modulate responses of trigeminal neurons evoked by N-methyl-D-aspartic acid and somatosensory stimuli

The present study investigated the modulation of N-methyl-D-aspartate (NMDA )-evoked and peripheral cutaneous stimulus-evoked responses of trigeminal n eurons by endomorphins, endogenous ligands for the mu-opioid receptor. Effe cts of endomorphins, administered microiontophoretically, were tested on th e responses of nociceptive neurons recorded in the superficial and deeper d orsal horn of the medulla (trigeminal nucleus caudalis) in anesthetized rat s. Endomorphin-1 and endomorphin-2 predominantly reduced the NMDA-evoked re sponses, producing an inhibitory effect of 54.1 +/- 2.96% (mean +/- SE; n = 34, P < 0.001) in 92% (34/37) of neurons and 63.6 +/- 3.61% (n = 32, P < 0 .001) in 91% (32/35) of neurons, respectively. The inhibitory effect of end omorphins was modality specific; noxious stimulus-evoked responses were red uced more than nonnoxious stimulus-evoked responses. Naloxone applied at io ntophoretic current that blocked the inhibitory effect of [D-Ala(2), N-Me-P he(4), Gly(5)-ol]-enkephalin, reduced the peak inhibitory effect of endomor phins on the NMDA- and natural stimulus-evoked responses. We suggest that e ndomorphins by acting at mu-opioid receptor selectively modulate noxious st imulus-evoked responses in the medullary dorsal horn.