Objective To investigate the effect of helminth-derived immunomodulatory glycan lacto-N-fucopentaose Ⅲ（LNFPⅢ） on the pathogenesis of neuropathic pain and spinal glial activation in the corresponding time windows after adult rat tibial nerve permanent transection (modified spared nerve injury, mSNI). Methods Ten weeks old male adult Sprague-Dawley (SD) rats weighing 250-300 g were randomly grouped into four groups: sham-operated group (n =6), mSNI group (n =6), mSNI plus bovine serum albumin (BSA) group (n =12) and mSNI plus LNFPⅢ group (n =12). Rats were subjected to surgical operation or sham operation on the right tibial nerves and were intraperitoneal injected BSA or LNEPⅢ-BSA conjugates by the group design. Animals from each group (n =6 per group) were subjected to the plantar test, von Frey hairs test, pinprick test and acetone test for critical evaluation of region-specific pain responses on the plantar sural and saphenous skin territories of ipsilateral and contralateral hindpaws after injuries. Transverse frozen sections of L3-4 spinal cords from the remaining animals of mSNI plus BSA group and mSNI plus LNFPⅢ group 7 and 14 d after injury (n =3 for each time point per group) were prepared and subjected to immunofluorescent staining of microglia/macrophage marker 〔cluster of differentiation molecule 11b (CD11b)〕 and astrocyte marker 〔glial fibrillary acidic protein (GFAP)〕, for analysis of spinal glial activation. Results After adult rat mSNI, early systematic administration of LNFPⅢ significantly but not completely attenuated region-specific pathological pain evoked by mechanical and thermal stimuli on the sural and saphenous skin territories of rat hindpaw plantar surfaces in acute (4/5 d after injuries) and subacute (7/8 d and 14/15 d after injuries) phases. Meanwhile, in the ipsilateral spinal cord dorsal horns, this early systematic treatment inhibited microglia/macrophage activation 7 d after injury and astrocyte activation 7 and 14 d after injury. Conclusion Early systematic administration of LNFPⅢ impairs the pathogenesis (acute induction and chronic transition) of neuropathic pain and spinal glial activation in the corresponding time windows after adult rat mSNI.
