Journavx (VX-548, Suzetrigine) was approved in 2025 as the only new non-opoid painkiller in the past two decades. As we know it is a Nav1.8 inibitor, here we explain why Nav1.8 inhibitors won’t cause addiction(Disclaimer: based on the current understanding o its mechanism.).The non-addictive nature of Nav1.8 inhibitors stems from their specific mechanism of action and where they exert their effects.
1. Peripheral vs. Central Nervous System Targeting:
- Nav1.8’s Location:
- Nav1.8 channels are predominantly expressed in the peripheral nervous system, specifically in sensory neurons of the dorsal root ganglia (DRG). These neurons are responsible for transmitting pain signals from the body to the spinal cord.
- This peripheral localization is crucial.
- Opioid’s Location:
- Opioids, in contrast, primarily act on receptors in the central nervous system (CNS), which includes the brain and spinal cord.
- The CNS is the seat of the reward pathways associated with addiction.
By targeting Nav1.8 in the periphery, inhibitors reduce pain signals before they reach the CNS. This avoids direct interaction with the brain’s reward centers, which are responsible for the euphoric effects and addictive potential of opioids.
2. Mechanism of Action:
- Nav1.8 Inhibition:
- Nav1.8 inhibitors block the activity of these specific sodium channels, preventing the transmission of pain signals along peripheral nerves.
- This action is focused on pain modulation, not on altering mood or producing euphoria.
- Opioid Action:
- Opioids bind to opioid receptors in the CNS, triggering the release of dopamine and other neurotransmitters that produce feelings of pleasure and reward.
- This activation of the reward system is a key driver of addiction.
3. Lack of CNS Penetration:
- Ideally, Nav1.8 inhibitors are designed to have limited or no penetration into the CNS. This further minimizes the risk of interacting with the brain’s reward pathways.
- It is important to note that any drug could have off target effects, and that all drugs should be used under the direction of a medical professional.
In essence:
- Nav1.8 inhibitors work by interrupting pain signals at their source in the peripheral nerves, rather than by altering brain chemistry.
- This peripheral targeting avoids the activation of the CNS reward pathways that underlie opioid addiction.
Therefore, the specific localization and mechanism of action of Nav1.8 inhibitors make them a promising alternative to opioids for pain management, with a significantly reduced risk of addiction.