Chronic pain remains a major global public health challenge. However, as our understanding of the mechanisms driving this condition advances, there are still few tools for effective, accurate, and optimal clinical management.
Therapeutic options remain limited, often accompanied by adverse side effects or a risk of substance dependence. Therefore research is actively seeking to identify new strategies and synergies, i.e., safe and non-addictive pain treatments; in this regard targeting voltage-gated sodium channels (Nav) in sensory neurons, key mediators of nociceptor excitability, and in particular Nav1.8, would be of interest. This is what a recent study by American researchers published in PNAS (Proceedings of the National Academy of Sciences) would suggest.
The Latest Evidence
The current work seems to provide further indication of the effective use of non-psychotomimetic cannabinoids, including cannabidiol (CBD), cannabigerol (CBG), and cannabinol (CBN) in controlling forms of pain that do not respond to traditional treatments or persist beyond six months, oriented toward established chronicity.
In particular the researchers’ work appears to demonstrate the inhibitory, effective action of Nav1.8, capable of categorizing and identifying the best type of cannabinoid and/or the action specificity that engages this channel. For example the study would highlight that CBG is a potent inhibitor of the excitability of dorsal root ganglion neurons, suggesting a potential non-addictive analgesic effect.
From here, the possible design and development of cannabinoid-based treatments for pain therapy, with particular attention to Nav1.8 inhibition as a therapeutic target.
What is the relationship and why focus specifically on this dynamic and this channel? First, one must distinguish between the psychological/emotional component of pain, which depends mainly on the neural circuits of the central nervous system (CNS), and the nociceptive component, which refers to the neural coding of tissue damage imminent or actual produced at the level of the peripheral nervous system. Depending on this distinction and action, much of the new drugs have currently focused on targets that sit within the nociceptive pathways, as their modulation is biologically more quantifiable and less subjective from patient to patient, thus offering the opportunity to hit peripheral channels not expressed in the CNS.
A “pathway” that opens the door to the development of non-addictive therapies, the main goal of scientific and pharmaceutical research. In this cluster, several members of the Nav channel family are included, where some molecular targets appear particularly promising for the development of new drugs: in the peripheral nervous system, the three main Nav channels identified are Nav1.7, Nav1.8 and Nav1.9, which work in concert, but each is responsible for different aspects of excitability in peripheral sensory neurons. The interaction of these three peripheral Nav channels in sensory neurons offers the opportunity to pharmacologically target different stages of excitability ignition, reducing pain symptoms without inducing psychoactive effects.
In Short
Although all subcategories have, to some extent, impacted pain reduction, the current results support that cannabinoid-induced inhibition of excitability is driven by the Nav1.8 pathway.
Source
Ghovanloo MR, Tyagi S, Zhao P et al. Nav1.8, an analgesic target nonpsychotomimic phytocannabinoids. PNAS, 2025, Vol. 122, No. 4, e2416886122. Doi: https://doi.org/10.1073/pnas.2416886122
Abbonati a Karla Miller
