Neuropathic pain (NP) is caused by a lesion or disease of the somatosensory system and is characterized by abnormal hypersensitivity to stimuli and nociceptive responses to non-noxious stimuli, affecting approximately 7-10% of the general population. However, current first-line drugs like non-steroidal anti-inflammatory agents and opioids have limitations, including dose-limiting side effects, dependence, and tolerability issues. Therefore, developing new interventions for the management of NP is urgent. In this study, we discovered that the high-frequency terahertz stimulation (HFTS) at approximately 36 THz effectively alleviates NP symptoms in mice with spared nerve injury. Computational simulation suggests that the frequency resonates with the carbonyl group in the filter region of Kv1.2 channels, facilitating the translocation of potassium ions. In vivo and in vitro results demonstrate that HFTS reduces the excitability of pyramidal neurons in the anterior cingulate cortex likely through enhancing the voltage-gated K+ and also the leak K+ conductance. This research presents a novel optical intervention strategy with terahertz waves for the treatment of NP and holds promising applications in other nervous system diseases.
Keywords: anterior cingulate cortex; high-frequency terahertz stimulation; mouse; neuropathic pain; neuroscience; potassium conductance; pyramidal neurons; spared nerve Injury.
Up to 1 in 10 people are estimated to experience neuropathic pain, a particularly challenging form of chronic pain where nerve damage causes extreme sensitivity to everyday stimuli. Current treatments often rely on painkiller drugs that can lead to serious side effects as well as dependency issues. New and effective interventions are therefore necessary. One radically different approach is the use of ‘terahertz’ waves, a type of electromagnetic radiation that has the ability to affect the chemical bonds holding molecules together. In fact, previous research has shown that specific frequencies of terahertz waves can modify the activity of certain proteins. With this technique, it may therefore be possible to disrupt voltage-dependent potassium channels, a type of proteins which help to regulate nerve cell activity and is a possible target for pain therapy. To explore this approach, Peng, Wang, Tan et al. investigated whether high-frequency terahertz stimulation that targets potassium ion channels could reduce neuropathic pain in mice. The animals, which had undergone surgery recreating nerve damage, were implanted with a device that allowed the delivery of terahertz waves into a brain region vital for regulating pain sensations. Experiments showed that delivering 36 terahertz radiations changed important ion channel properties (such as how easily they would allow ions to pass through), decreasing neuron activity and raising the pain threshold of the mice. This finding indicates that, with further development, terahertz frequency stimulation could become a new, non-drug method to manage neuropathic pain. Additional research will be needed to see if terahertz waves could also be applied to other neurological disorders influenced by ion channel activity.
© 2024, Peng, Wang, Tan et al.