Widespread enhancement of pain sensitivity in MRL/MpJ mice following infraorbital nerve transection

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 neuropathic pain following infraorbital nerve transection and investigate the mechanisms underlying wide-spread pain.METHODS The infraorbital 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 including the vibrissal pads,hindpaws,and tail were tested after surgery.Activation of microglia in the dorsal horn at levels of medulla(MDH) and L4/L5(SDH) were measured by immunohistochemistry.RESULTS Compared to sham-operated mice,injured mice showed significantly mechanical allodynia,heat allodynia and hyperalgesia in the ipsilateral vibrissal pad,and extraterritorially 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 postoperatively.However,the activation of microglia in L4/L5 SDH occurred until 7 d postoperatively.Moreover,intraperitoneal injection 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.Microglia activation may be involved in the mechanisms of this phenomenon.