Origins of GABA B receptor-like immunoreactive terminals in the rat spinal dorsal horn

Abstract

By means of immunohistochemistry for γ-aminobutyric acid receptor B subtype (GABA BR), the origins of GABA BR-like immunoreactive (GABA BR-LI) terminals in the rat spinal dorsal horn were investigated. After dorsal root rhizotomy and/or spinal cord hemisection, the densities of GABA BR-LI terminals were remarkably depleted in the ipsilateral superficial dorsal horn of relevant segments, whereas GABA BR-LI neurons and sparsely distributed GABA BR-LI terminals remained. After injection of Fluoro-Gold (FG) into the left side of superficial lumbar dorsal horn, FG retrograde-labeled neurons were mainly observed in the ipsilateral rostral ventromedial medulla (RVM) and brainstem raphe nuclei. Some of the FG-labeled neurons, especially in the RVM, exhibited GABA BR-like immunoreactivity. Additionally, immunofluorescence histochemical double-staining revealed that the majority of GABA BR-LI neurons in the periaqueductal gray (PAG), RVM and brainstem raphe nuclei showed 5-hydroxytryptamine (5-HT)-like immunoreactivity. The present study morphologically proves that GABA BR-LI terminals in the spinal dorsal horn originate from peripheral afferents, intrinsic neurons and supraspinal structures; GABA BR and 5-HT co-exist in many neurons in the PAG, RVM and brainstem raphe nuclei. Considering that PAG, RVM, brainstem raphe nuclei and spinal dorsal horn are important structures involved in the pain modulation, we suggest that the descending pain modulation system might be mediated, at least in part, by GABA BR.