The organisation of spinoparabrachial neurons in the mouse.

Darren Cameron,Maria Gomez-Lima,Andrew J Todd,Maria Gutierrez-Mecinas,Masahiko Watanabe,Erika Polgár

doi:10.1097/j.pain.0000000000000270

Darren Cameron, Maria Gomez-Lima + Show 4 more

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https://doi.org/10.1097/j.pain.0000000000000270

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Abstract

The anterolateral tract (ALT), which originates from neurons in lamina I and the deep dorsal horn, represents a major ascending output through which nociceptive information is transmitted to brain areas involved in pain perception. Although there is detailed quantitative information concerning the ALT in the rat, much less is known about this system in the mouse, which is increasingly being used for studies of spinal pain mechanisms because of the availability of genetically modified lines. The aim of this study was therefore to determine the extent to which information about the ALT in the rat can be extrapolated to the mouse. Our results suggest that as in the rat, most lamina I ALT projection neurons in the lumbar enlargement can be retrogradely labelled from the lateral parabrachial area, that the majority of these cells (∼ 90%) express the neurokinin 1 receptor (NK1r), and that these are larger than other NK1r-expressing neurons in this lamina. This means that many lamina I spinoparabrachial cells can be identified in NK1r-immunostained sections from animals that have not received retrograde tracer injections. However, we also observed certain species differences, in particular we found that many spinoparabrachial cells in laminae III and IV lack the NK1r, meaning that they cannot be identified based solely on the expression of this receptor. We also provide evidence that the majority of spinoparabrachial cells are glutamatergic and that some express substance P. These findings will be important for studies designed to unravel the complex neuronal circuitry that underlies spinal pain processing.

Highlights

Nociceptive, thermal, and pruritic information is conveyed from spinal cord to brain through the anterolateral tract (ALT).[50]
The spinal cord injections were located in the L3 and L4 segments, and in both cases, these filled most of laminae I-III of the ipsilateral dorsal horn (Fig. 1C-E) at the levels of the injection
The main findings of this study are that (1) spinoparabrachial cells account for ;5% of lamina I neurons in mouse lumbar enlargement; (2) ;90% of these cells are NK1r1, and they are generally larger than other NK1r1 neurons in this lamina; (3) only a minority of giant lamina I cells are labelled from the lateral parabrachial area (LPb); (4) many laminae III and IV spinoparabrachial neurons lack the neurokinin 1 receptor (NK1r), but as in the rat, they are innervated by both CGRPand neuropeptide Y (NPY)-containing axons; and (5) spinoparabrachial axons originating from the superficial dorsal horn are most glutamatergic, with some expressing substance P (SP)

Summary

Introduction

Nociceptive, thermal, and pruritic information is conveyed from spinal cord to brain through the anterolateral tract (ALT).[50] Cells of origin of the ALT are concentrated in lamina I and scattered throughout the deeper laminae (III-VI). Their supraspinal targets include thalamus, periaqueductal grey (PAG) matter, lateral parabrachial area (LPb), and certain medullary nuclei. Quantitative studies in rat lumbar enlargement have demonstrated that ALT projection cells account for ;5% of lamina I neurons.

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