The Mechanism Underlying The Regulation Of Endomorphins On The Periphery Nociceptive Information Transmission In The Superficial Laminae Of The Rat Spinal Dorsal Horn

Endomorphin-1 (EM-1) and endomorphin-2 (EM-2) are endogenous ligands for μ-opioid receptors (MOR). Activation of MOR results in inhibiting adenylate cyclase, opening inwardly-rectifying K+ channel of neurons in substantia gelatinosa (SG) and inhibiting Ca2+ currents of neurons in dorsal root ganglia. Both EM-1 and MOR are densely distributed in the superficial laminae of spinal dorsal horn. Superficial laminae (laminae I, II) of spinal dorsal horn are the first termination site of the peripheral nociceptive information, which is relayed and integrated here and then sent to higher centers by projection neurons. Substance P (SP) is a major neurotransmitter for the transmission of nociceptive information in the primary afferent terminals in the superficial laminae of the spinal dorsal horn and most SP containing fibers and terminals also express MOR. There is much evidence showing that EMs plays a significant analgesic role at spinal level. However, the cellular mechanisms underlying the actions of EMs on nociceptive informationtransmission in the spinal cord are still unknown. Thus, by use of the blind whole-cell voltage-clamp recording technique, the present study firstly investigated the effects of EMs on synaptic transmission in the SG of adult rat at the synaptic level. Secondly, we examined the effects of EMs on the release of SP from primary afferent terminals to the superficial laminae of the spinal dorsal horn, which might contribute to better understand the mechanisms of EMs analgesic effect at spinal level.The results showed that: (1) EMs inhibited both excitatory and inhibitory synaptic transmission in the SG. Both EM-1 (1 μM) and EM-2 (1 μM) remarkably reduced the frequency but not the amplitude of miniature excitatory postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs). These effects were antagonized by P-funaltrexamine (β-FNA, 10 μM), a selective opioid receptor antagonist. These results indicate that EMs suppress both excitatory and inhibitory synaptic transmission by activating presynaptic u-opioid receptors in the SG. (2) EMs decreased the release of SP from primary afferent terminals to the superficial laminae of the spinal dorsal horn. After complete blockade of glutamate receptor-mediated currents, stimulation with high frequency and high intensity on the attached dorsal root induced slow residual EPSCs (19%) in some neurons (16/81) in the superficial laminae of the spinal dorsal horn. These EPSCs could be blocked by 5 uM L-732138 (a selective NK1 receptor antagonist). Both EM-1 and EM-2 could dose-dependently inhibited the EPSCs induced by stimulating the attached dorsal root. The amplitude of the residual EPSCs was increased...