Targeted antibody therapy provides long-lasting relief from neuropathic pain

Pain is a natural protective mechanism that alerts the body to actual or potential injury. But when nerves themselves are damaged, they can generate abnormal pain signals even in the absence of a new injury. This condition, known as neuropathic pain, can be persistent and difficult to treat. Medicines can sometimes provide inadequate relief or cause unwanted effects, leading to a need for treatment that can reduce abnormal pain without interfering with normal pain sensation. 

To address this, the researchers targeted a protein called Nav1.7, a voltage-gated sodium channel expressed in sensory neurons that contributes to the transmission of electrical signals involved in pain. The study, conducted by Associate Professor Daisuke Uta of the University of Toyama and Dr. Sosuke Yoneda of Shionogi & Co., Ltd., investigated whether antibodies designed to specifically target Nav1.7 could provide long-lasting relief from neuropathic pain. The findings were published in Volume 18 of Pharmaceutics on June 21, 2026. 

NaV1.7 is a specialized sodium ion channel in nerve cells that plays an important role in sensing and transmitting pain signals."

Dr. Daisuke Uta, Associate Professor, University of Toyama

The team developed humanized antibodies that could recognize Nav1.7. They started with testing the antibodies in cells to determine whether they could bind specifically to the target and inhibit its function. The results showed that the antibodies selectively bound to Nav1.7 and reduced the electrical activity of nerve cells involved in pain signaling. In particular, Clone1 and S-151128 showed strong binding to Nav1.7 while exhibiting at least 650-fold and 1300-fold selectivity, respectively, over the other Nav subtypes tested. 

The researchers also tested the antibodies in rats with partial sciatic nerve ligation (PSNL), a model of neuropathic pain. The antibodies were administered intravenously rather than locally into the nerves or spinal cord. Both antibodies resulted in reduced animal sensitivity to mechanical stimulation in a dose-dependent manner. At certain doses, their effects were comparable to pregabalin, a commonly used treatment for neuropathic pain. Most notably, the analgesic effects of the antibodies remained stronger than those of pregabalin 96 hours after treatment. 

The study also looks beyond animal behavior to understand what happens in their nervous systems. In rats with nerve injury, spinal dorsal horn neurons showed increased spontaneous activity and increased responses to mechanical stimulation. The antibody treatment reduced both types of activity. The researchers also observed fewer dorsal root ganglion neurons showing mechanically induced phosphorylation of extracellular signal-regulated kinase (pERK), a marker of neuronal activation, providing additional evidence that the treatment was suppressing abnormal pain signaling. 

Coming to the most important question, whether blocking Nav1.7 could also interfere with normal, protective pain sensation, researchers tested animals without nerve injury. The results showed that none of the antibodies significantly changed their responses to mechanical stimulation. The movements were assessed using a rotating-rod test as well. While the comparison drug pregabalin showed impaired performance at the tested dose, the antibodies did not significantly affect motor function. 

"Targeting Nav1.7 could help silence abnormal pain signals while preserving normal protective pain sensation," notes Dr. Uta. 

The findings suggest that targeting Nav1.7 with antibodies could potentially distinguish abnormal pain caused by nerve damage from normal protective pain sensation. Another notable feature of the approach is the extent of relief. The long-lasting pain relief observed in the rat model highlights the potential of this approach as a treatment strategy for neuropathic pain. 

As the findings are still preclinical, the researchers were unable to accurately measure how much antibody reached the injured nerve. In addition, the treatment was evaluated in only one neuropathic pain model, highlighting the need for further studies to determine whether the findings can be replicated in other models. Nevertheless, the study provides preclinical evidence for a potential new strategy for treating neuropathic pain. Remarkably, the papers also report that S-151128, one of the antibodies studied, is currently in clinical trials, marking an important step towards determining whether the promising effects seen in animals can be used as a treatment for people.