[Increased expression of formalin-induced Fos and NADPH-d positive neurons in the spinal cord of morphine-tolerant rats].

Fos immunocytochemistry, NADPH-d histochemistry and Fos/NADPH-d double-labeling method were used to study the changes in formalin-induced Fos, NADPH-d positive and Fos/NADPH-d double-labeled neurons in the spinal cord of morphine-tolerant rats. Formalin-induced Fos-like immunoreactivity (Fos-LI) was located in the superficial laminae and neck of ipsilateral spinal cord. Acute administration of morphine decreased the expression of Fos-LI in non-tolerant rats, while the expression of Fos-LI was significantly increased in morphine-tolerant rats. Fos-LI was distributed not only in the whole laminae of the ipsilateral spinal cord but also in the contralateral spinal cord. Acute administration of morphine was ineffective in decreasing the expression of Fos-LI in morphine-tolerant rats. Morphine tolerance increased the expression of formalin-induced NADPH-d positive neurons in the superficial laminae of spinal dorsal horn. A few formalin-induced Fos/NADPH-d double-labeled neurons were detected in the superficial laminae of spinal dorsal horn of non-tolerant rats. In morphine-tolerant rats, on the other hand, formalin-induced Fos/NADPH-d double-labeled neurons were increased and distributed in the whole laminae of the ipsilateral spinal cord and the contralateral superficial spinal cord. It is suggested that NO is involved in the increase of formalin-induced Fos-LI in the spinal cord of morphine-tolerant rats and may play an important role in the development of morphine tolerance.