Neuropathic pain is a worldwide problem that causes physical and psychological pain to many patients. 3-acetylaconitine (AAC) is a kind of non-narcotic analgesic with long-lasting action, non-tolerant and non-addiction. However, it has some cardiac toxicity and can easily cause toxic organ damage. To solve these problems, soluble microneedle patches were prepared and delivered subcutaneously through the skin barrier with a low drug load. The results showed that the solid dispersion made with AAC and PVP effectively changed the solubility of AAC and improved its bioavailability. AAC-MN had good morphology, good mechanical properties and transdermal properties, and no skin irritation. Through the use of the neuropathic pain model (spared nerve injury, SNI) test, found that the soluble microneedle mediated AAC hypodermic delivery provides effective analgesic activity. AAC/PVP-MN could increase the model group mechanical pain threshold and hind legs load-bearing capacity, reduce the inflammation in the body, and have certain protective effect to spinal cord neurons. This study provided an idea for the clinical treatment of neuropathic pain and also a new approach for the safe use of toxic drugs with a narrow range.