Objective To investigate the changes in the expression of phosphor-p38 mitogen-activated protein kinase (p-p38MAPK) in the distal cerebrospinal fluid contacting neurons (CSF-CNs) in rats with neuropathic pain.Methods Forty-eight male adult SD rats aged 2-3 months weighing 230-270 g were randomly divided into 2 groups (n =24 each): sham operation group (group S) and chronic constrictive injury group (group CCI).Neuropathic pain was induced by CCI.Sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 silk thread.Thermal withdrawal latency (TWL) was measured with radiation heat stimulus before (baseline) and 1,3,5,7,14 d after CCI in 4 animals at eachtime point in each group.The animals were then sacrificed.30％ cholera toxin subunit B with horse radish peroxidase 3 μl was injected into the lateral ventricle at 48 h before the animals were sacrificed at each time point.The brain tissue in the region of the midbrain aqueduct was taken.The number of distal CSF-CN expressing p-p38MAPK was calculated.p-p38MAPK was detected by histochemical staining.Results The TWL was significantly shortened at 1-14 d after CCI in group CCI as compared with group S.The number of distal CSF-CNs expressing p-p38MAPK was significantly increased at 5-14 d after CCI in group CCI as compared with group S.Conclusion The distal CSF-CNs may be involved in the neuropathic pain induced by CCI through p38MAPK signaling pathway.p38MAPK may contribute only to the maintenance but not development of neuropathic pain.