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 neurons by endomorphins, endogenous ligands for the μ-opioid receptor. Effects of endomorphins, administered microiontophoretically, were tested on the responses of nociceptive neurons recorded in the superficial and deeper dorsal horn of the medulla (trigeminal nucleus caudalis) in anesthetized rats. Endomorphin-1 and endomorphin-2 predominantly reduced the NMDA-evoked responses, 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 endomorphins was modality specific; noxious stimulus-evoked responses were reduced more than nonnoxious stimulus-evoked responses. Naloxone applied at iontophoretic current that blocked the inhibitory effect of [d-Ala2,N-Me-Phe4, Gly5-ol]-enkephalin, reduced the peak inhibitory eff...