Abstract
Around a quarter of neurons in laminae I–II of the dorsal horn are inhibitory interneurons. These play an important role in modulating somatosensory information, including that perceived as pain or itch. Previous studies in rat identified four largely non-overlapping neurochemical populations among these cells, defined by expression of galanin, neuropeptide Y (NPY), neuronal nitric oxide synthase (nNOS) or parvalbumin. The galanin cells were subsequently shown to coexpress dynorphin. Several recent studies have used genetically modified mice to investigate the function of different interneuron populations, and it is therefore important to determine whether the same pattern applies in mouse, and to estimate the relative sizes of these populations. We show that the neurochemical organization of inhibitory interneurons in mouse superficial dorsal horn is similar to that in the rat, although a larger proportion of these neurons (33%) express NPY. Between them, these four populations account for ∼75% of inhibitory cells in laminae I–II. Since ∼25% of inhibitory interneurons in this region belong to a novel calretinin-expressing type, our results suggest that virtually all inhibitory interneurons in superficial dorsal horn can be assigned to one of these five neurochemical populations. Although our main focus was inhibitory neurons, we also identified a population of excitatory dynorphin-expressing cells in laminae I–II that are largely restricted to the medial part of the mid-lumbar dorsal horn, corresponding to glabrous skin territory. These findings are important for interpretation of studies using molecular-genetic techniques to manipulate the functions of interneuron populations to investigate their roles in somatosensory processing.
Highlights
The spinal dorsal horn receives sensory input from a wide variety of primary afferents, including nociceptors, pruritoceptors, thermoreceptors and low-threshold mechanoreceptors, and these terminate in a highly organized pattern within specific laminae (Todd, 2010, 2017; Abraira and Ginty, 2013; Braz et al, 2014)
We have previously reported that inhibitory (GABA-immunoreactive) cells account for 25.8% of all neurons in laminae I–II and 37.6% of those in lamina III (Polgar et al, 2013a)
The main findings of this study are: (1) that NPYimmunoreactivity is restricted to inhibitory interneurons in laminae I–III, but is present in a far higher proportion (33%) of these cells than we found in the rat; (2) that PPD expression largely overlaps with that of galanin, and shows $10% co-localization with neuropeptide Y (NPY); (3) that as in the rat, NPY, neuronal nitric oxide synthase (nNOS) and parvalbumin inhibitory interneuron populations show little or no overlap; and (4) that the distribution of inhibitory PPD cells in laminae I–II appears uniform, the pattern is quite different for excitatory PPD cells, which are clustered in the medial third of the dorsal horn at the L4 level, corresponding to the region innervated from glabrous skin
Summary
The spinal dorsal horn receives sensory input from a wide variety of primary afferents, including nociceptors, pruritoceptors, thermoreceptors and low-threshold mechanoreceptors, and these terminate in a highly organized pattern within specific laminae (Todd, 2010, 2017; Abraira and Ginty, 2013; Braz et al, 2014). Quantitative studies in the mouse have shown that the inhibitory interneurons account for around one quarter of the neurons in lamina I–II and $40% of those in lamina III. These cells are known to have an important role in suppressing pain and itch, and loss of this function is thought to contribute to pathological pain states (Yaksh, 1989; Coull et al, 2003; Sandkuhler, 2009; Kardon et al, 2014; Foster et al, 2015; Petitjean et al, 2015)
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