Alkali burn induced corneal spontaneous pain and activated neuropathic pain matrix in the central nerve system in mice

Purpose: To explore whether alkali burn causes corneal neuropathic pain and activates neuropathic pain matrix in the central nerve system in mice. Methods: A corneal alkali burn mouse model (grade II) was used. Mechanical threshold in the cauterized area was tested using Von Frey hairs. Spontaneous pain behavior was investigated with conditioned place preference (CPP). Phosphor extracellular signal-regulated kinase (ERK), which is a marker for neuronal activation in chronic pain processing, was investigated in several representative areas of the neuropathic pain matrix: the two regions of the spinal trigeminal nucleus (subnucleus interpolaris/caudalis ,Vi/Vc; subnucleus caudalis/upper cervical cord , Vc/C1), insular cortex, anterior cingulated cortex (ACC), and the rostroventral medulla (RVM). Further, pharmacologically blocking pERK activation in ACC of alkali burn mice was performed in a separate study. Results: Corneal alkali burn caused long lasting damage to the corneal subbasal nerve fibers and mice exhibited spontaneous pain behavior. By testing in several representative areas of neuropathic pain matrix in the higher nerve system, phosphor extracellular signal-regulated kinase (ERK) was significantly activated in Vc/C1, but not in Vi/Vc. Also, ERK was activated in the insular cortex, ACC, and RVM. Furthermore, pharmacologically blocking ERK activation in ACC abolished alkali burn induced corneal spontaneous pain. Conclusion: Alkali burn could cause corneal spontaneous pain and activate neuropathic pain matrix in the central nerve system. Furthermore, activation of ERK in ACC is required for alkali burn induced corneal spontaneous pain