OBJECTIVE Neuropathic pain in humans may spread to regions beyond the area innervated by the injured nerve.This study aims to verify the appearance of wide-spread neuropath ic pain following infraorbital nerve transection and investigate the mechanisms underlying wide-spread pain.METH ODS The in fraorbital nerve of male MRL/MPJ mice was transected (ION-T)to induce trigeminal neuralgia under isoflurane anesthesia.The sensitivities to tactile and heat stimuli of different body parts in cluding the vibrissal pads, hindpaws, and tail were tested after surgery.Activation of microglia in the dorsal hom at levels of me dulla (MDH) and L4/IS(SDH) were measured by immunohisto chemistry.RESULTS Compared to sham-operated mice, in jured mice showed significantly mechanical allodynia, heat allo dynia and hyperalgesia in the ipsilateral vibrissal pad, and extra territorially in the contralateral vibrissal pad, bilateral hindpaws and tail.There was a negative correlation between the evoked pain in denervated area and extraterritorial areas.Microglia in the MDH of injured mice were significantly activated 3 d postopera tively.However, the activation of microglia in L4/L5 SDH oc curred until 7 d postoperatively.Moreover, intraperitoneal injec tion of minocycline inhibited the wide-spread pain abnormalities in the vibrissal pads, hindpaws, and tail.CONCLUSION These results indicate the appearance of wide-spread neuropathic pain following infraorbital nerve transection.Micrnglia activation may be involved in the mechanisms of this phenomenon.