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. 2023 Mar 1;4:1114428. doi: 10.3389/fpain.2023.1114428

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© 2023 Ntalouka and Tsirivakou.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Pain pathways: transduction-transmission-perception-modulation. Transduction refers to activation of peripheral nociceptors (primary afferent neurons) from various stimuli. Cell bodies of nociceptors neurons are located in the dorsal root ganglia (DRG) (innervating the skin, deep tissues, visceral organs) and trigeminal ganglia (innervating the face). Nociceptors express transducers on their distal terminus, which are high-threshold ion channels, such as transient receptor potential ion channels [TRPs, ATP- gated ion channels, and acid-sensing ion channels (ASIC)]. These are responsible for converting the stimuli to action potential (AP). Next is the transmission process during which primary afferent neurons transmit the AP to the spinal cord, via their axons that terminate in the spinal dorsal horn (DH). Perception refers to the projection of pain signals in the brain, during which complex neuronal networks in the brain receive and “translate” from the spinal cord information about duration, location, and intensity of pain. Modulation is the process by which the nervous system either enhances or inhibits pain signals. Alteration of pain impulses occurs due to three endogenous mechanisms. 1. Segmental inhibition during which the inhibitory nerve in the spinal cord can be blocked to transmit noxious stimuli from C-fibers as a result of stimulation of the non-noxious Aβ fibers nociceptors (the “gate theory”). The method of pain management with transcutaneous electrical nerve stimulation is based on this theory. 2. The opioid system consists of opioid receptors in the brain, spinal cord and peripheral nerves that are activated by the binding of endogenous opioids (enkephalins, endorphins, and dynorphins). 3. The descending inhibitory nerve system, projecting via the midbrain, inhibits nociceptive transmission at the spinal cord dorsal horn.