Abstract:Objective: To investigate if the NADPH d positive neurons in dorsal raphe nucleus (DR) were involved in modulation of sigmoid pain. Methods: The Fos immunocytochemistry, NADPH d histochemistry and Fos LI /NADPH d double labeling methods were used to study the changes in NADPH d positive neurons and Fos LI in dorsal raphe nucleus (DR) of rats after formalin stimulation. Results: After the injection of formalin into the sigmoid wall, the expression of NADPH d positive neurons and the staining degree in the DR were increased remarkably; the expression of Fos like immunoreactivity (Fos LI) in DR was increased significantly; and about 11% Fos LI /NADPH d double labeled neurons were detected in NADPH d positive neurons in the DR. Conclusion: NADPH d positive neurons may be involved in the processing of pain induced by injecting formalin into the sigmoid wall in rats.