Distribution of antinociceptive adenosine a 1 receptors in the spinal cord dorsal horn, and relationship to primary afferents and neuronal subpopulations

Abstract

Adenosine can reduce pain and allodynia in animals and man, probably via spinal adenosine A 1 receptors. In the present study, we investigate the distribution of the adenosine A 1 receptor in the rat spinal cord dorsal horn using immunohistochemistry, in situ hybridization, radioligand binding, and confocal microscopy. In the lumbar cord dorsal horn, dense immunoreactivity was seen in the inner part of lamina II. This was unaltered by dorsal root section or thoracic cord hemisection. Confocal microscopy of the dorsal horn revealed close anatomical relationships but no or only minor overlap between A 1 receptors and immunoreactivity for markers associated with primary afferent central endings: calcitonin gene-related peptide, or isolectin B4, or with neuronal subpopulations: μ-opioid receptor, neuronal nitric oxide synthase, met-enkephalin, parvalbumin, or protein kinase Cγ, or with glial cells: glial fibrillary acidic protein. A few adenosine A 1 receptor positive structures were double-labeled with α-amino-3-hydroxy-5-methyl-4-isoaxolepropionic acid glutamate receptor subunits 1 and 2/3. The results indicate that most of the adenosine A 1 receptors in the dorsal horn are located in inner lamina II postsynaptic neuronal cell bodies and processes whose functional and neurochemical identity is so far unknown. Many adenosine A 1 receptor positive structures are in close contact with isolectin B4 positive C-fiber primary afferents and/or postsynaptic structures containing components of importance for the modulation of nociceptive information.