Tacrine alleviates neuropathic pain in mice by mimicking the cell adhesion molecule L1

Neuropathic pain, which is caused by nervous system damage or dysfunctions, remains one of the most intractable challenges in modern medicine due to the lack of effective drugs. Tacrine, which is a small organic compound, is known to mimic the beneficial characteristics of the neural cell adhesion molecule L1 (L1CAM, L1) in vitro. Although previous studies indicated that L1 constitutes a viable strategy for promoting regeneration after nervous system injury, it is not clear whether L1 has a definite role in peripheral nerve injury. In this study, we observed that tacrine eased thermal hyperalgesia and mechanical allodynia after sciatic nerve chronic construction injury and restored functional morphological damage. Furthermore, tacrine suppressed the proliferation and activation of glia and reduced the level of IL-1 beta, IL-6 and TNF-alpha. Tacrine also inhibited the JAK2/STAT3 signaling pathway, which is involved in neuroinflammation. These observations indicated that tacrine is a promising candidate for an analgesic agent for neuropathic pain.