Fig. 1.
Schematic diagram showing the mechanism of opiorphin action in enkephalin-related opioid pathways: (A) nociceptive information (red lightning) is transmitted from the periphery to the spinal dorsal horn by primary sensory neurons. At the spinal level, these neurons transmit nociceptive signals to second order neurons in the brain. Enkephalins (purple dots) are present at the different levels of signal transmission from the periphery to the brain. (B) Enkephalins are released in response to nociceptive information. They can either bind to opioid receptors, thus reducing the nociceptive transmission, or they can be catabolized by membrane aminopeptidase-N (APN) and neutral endopeptidase (NEP) enkephalinases, localized in close proximity to the opioid receptors. If the trauma induces significant danger, the nociceptive signal (red lightning) is transmitted to upper brain levels (solid red arrow), due to insufficient levels of enkephalins capable of binding to opioid receptors. The presence of opiorphin helps modulate nociceptive signal transmission at peripheral, spinal, and central levels. (C) In the case of painful stimuli, the administration of opiorphin leads to an increase in the bioavailability of opioid receptor–binding enkephalins by inhibiting enkephalin degradation and thus blocking the transmission (slashed red arrow) of nociceptive signals (red lightning).