Liu et al. conducted a study on rats to investigate the neural mechanisms involved in pain processing and modulation. Using behavioral assays and calcium imaging techniques, they sought to understand how oxytocin signaling from the hypothalamus affects nociceptive coding in the prefrontal cortex (PFC). The study found that oxytocin amplifies the nociceptive response in the population of neurons in the prelimbic prefrontal cortex (PL-PFC), which helps to alleviate acute and chronic pain in rats. The oxytocinergic projection from the paraventricular nucleus (PVN) to the PL-PFC plays a crucial role in regulating pain by modulating the balance between excitation and inhibition in the PL-PFC. These findings provide new insights into the neural mechanisms involved in pain modulation and may have important implications for the development of innovative treatments for chronic pain disorders.