Neurokinin 1 receptor expression by neurons in laminae I, III and IV of the rat spinal dorsal horn that project to the brainstem

TLDR

Large NK1 receptor–expressing neurons in laminae III and IV of the rat spinal dorsal horn receive substance P from nociceptive afferents and are known to project to the thalamus, but other projection targets are poorly understood. This study aimed to determine whether all such NK1R neurons are projection neurons and to identify the brainstem regions they innervate, including lamina I neurons. Retrograde labeling was performed by injecting cholera toxin B subunit into four brainstem nuclei, and the proportion of NK1R neurons in spinal segment L4 that were labeled was quantified. Over 90 % of these neurons project to the contralateral lateral reticular nucleus, more than 60 % to the lateral parabrachial area, some to the dorsal caudal medulla, few to the periaqueductal gray, and most lamina I NK1R neurons also project, indicating that NK1R dorsal horn neurons participate in multiple pain‑related ascending pathways.

Abstract

Abstract Large neurons in laminae III and IV of the spinal cord which express the neurokinin 1 receptor and have dendrites that enter the superficial laminae are a major target for substance P (SP)‐containing (nociceptive) primary afferents. Although some of these neurons project to the thalamus, we know little about other possible projection targets. The main aim of this study was to determine whether all cells of this type are projection neurons and to provide information about brainstem sites to which they project. Injections of cholera toxin B subunit were made into four brainstem areas that receive input from the spinal cord, and the proportion of cells of this type in the L4 spinal segment that were retrogradely labelled was determined in each case. The results suggest that most of these cells (>90%) project to the contralateral lateral reticular nucleus (or to a nearby region), while many (>60%) send axons to the lateral parabrachial area and some to the dorsal part of the caudal medulla. However, few of these cells project to the periaqueductal grey matter. As lamina I neurons with the neurokinin 1 receptor appear to be important in the generation of hyperalgesia, we also examined projection neurons in this lamina and found that for each injection site the great majority possessed the receptor. These results demonstrate that dorsal horn neurons which express the neurokinin 1 receptor contribute to several ascending pathways that are thought to be important in pain mechanisms.