?- and ?-opioid receptor mRNAs are expressed in spinally projecting serotonergic and nonserotonergic neurons of the rostral ventromedial medulla

Abstract

The rostral ventromedial medulla (RVM) is an important mediator of the supraspinal component of opioid antinociception. Previous studies have suggested that activation of the cloned μ‐ and δ‐opioid receptors (MOR1 and DOR1 respectively) in the RVM produces the antinociception mediated by spinally projecting neurons. In the present study, we investigated the expression of mRNA encoding either MOR1 or DOR1 in the RVM of rats. In addition, we examined quantitatively the expression of MOR1 and DOR1 mRNAs in spinally projecting RVM neurons including serotonergic (5HT) cells by using in situ hybridization, immunocytochemistry, retrograde tract‐tracing, and the physical disector. Brainstem neurons were labeled in 14 male Sprague‐Dawley rats by applying Fluoro‐Gold (FG) topically to the dorsal surface of the lumbosacral spinal cord. Five‐micrometer‐thick cryostat sections were cut and in situ hybridization was performed by using full‐length cRNA probes labeled with 35S‐UTP. We found that 43% of RVM projection neurons expressed MOR1 mRNA and 83% of RVM projection neurons expressed DOR1 mRNA. Of 192 retrogradely labeled cells in the RVM, 51 cells (27%) were immunoreactive for 5HT. Of this population, half appeared to be labeled for the mRNA encoding MOR1 and over three‐fourths appeared to be labeled for the mRNA encoding DOR1. Thus, we conclude that bulbospinal neurons express MOR1 and DOR1; moreover, MOR1 and DOR1 are expressed by significant proportions of 5HT neurons projecting to or through the dorsal spinal cord. J. Comp. Neurol. 404:183–196, 1999. © 1999 Wiley‐Liss, Inc.

Central serotonergic neurons are differentially required for opioid analgesia but not for morphine tolerance or morphine reward

“…Because all three classes of opioid receptors are expressed in 5-HT neurons (4,31,32), it remains to be determined to what degree and in what way the loss of each individual opioid receptor in 5-HT neurons may have contributed to the altered behavioral phenotype of Lmx1b f/f/p mice. Obviously, it is possible that the attenuation of morphine analgesia in Lmx1b f/f/p mice could be due to a secondary change of MOR expression in other regions of the brain.…”

The neuroanatomy of sexual dimorphism in opioid analgesia

“…Indeed, the average number of retrogradely labeled cells across the rostrocaudal extent of the PAG was 33% greater in female compared to male rats. The most prominent sex difference in retrograde labeling was observed within the lateral and ventrolateral regions of the caudal PAG, an area known to contain a dense distribution of mu opioid receptors [51, 90]. …”

Injury Induced Activation of Extracellular Signal-Regulated Kinase (ERK) in the Rat Rostral Ventromedial Medulla (RVM) is Age Dependant and Requires the Lamina I Projection Pathway

“…Although only NEUTRAL- cells have been reported to contain 5HT [31], ON- and OFF cells have been shown to receive a strong serotonergic innervation, indicating that serotonin could both directly and indirectly control pain processing at the brainstem and spinal level [32,33]. Also, some serotonergic neurons express the mu opiate receptor [34] which has previously been suggested to be characteristic of non-5HT ON- cells. Specific ablation of RVM mu receptor expressing neurons by dermorphin-saporin conjugates alleviated pain states and would be expected to lesion both subsets of 5HT and non-5HT containing ON- cells.…”