Mu- and delta-opioid receptors are downregulated in the largest diameter primary sensory neurons during postnatal development in rats

Abstract

The aim of this study was to investigate the postnatal development of mu-(MOR) and delta-opioid receptor (DOR) immunoreactivity in rat dorsal root ganglia. Lumbar dorsal root ganglia (DRG) from postnatal day (P) 0, 3, 7 and 21 rat pups were immunostained for MOR and DOR. Proportions of MOR +ve and DOR +ve cells were calculated from profile counts. Diameters of MOR +ve and DOR +ve cells were measured and compared to -ve cells. The coexpression of MOR and neurofilament (NF200) in DRG over this postnatal period was also investigated. A greater proportion of cells were immunoreactive for MOR and DOR in neonatal rat DRG at P0, P3 and P7 compared to P21. At P3, 39.5+/-1.7% of cells were MOR +ve and 30.3+/-1.5% were DOR +ve, whereas at P21, the values were 30.1+/-1.7% and 21.8+/-1.6% (mean+/-SEM), respectively. During the first postnatal week both opioid receptors were expressed in cells across the whole diameter range but by 3 weeks of age, expression was restricted to small and medium diameter cells. Furthermore, a significantly higher proportion of NF200 +ve cells expressed MOR in new-born compared to P21 rats. The results show that MOR and DOR expression is downregulated in the largest diameter, NF200 +ve primary sensory neurons postnatally. Since these neurons are mainly non-nociceptive, this may explain previous reports of opioid agonists affecting reflex responses to both innocuous and noxious stimuli in rat pups. The results highlight an important difference between opioid function in the immature and adult nervous system.

Proinflammatory Chemokines, Such as C-C Chemokine Ligand 3, Desensitize μ-Opioid Receptors on Dorsal Root Ganglia Neurons

“…Furthermore, long-term exposure to proinflammatory chemokines compromises the function of MORs on sensory neurons of dorsal root ganglia. MORs are preferentially expressed on small to medium diameter neurons (32). Our data from immunohistochemical staining clearly showed that CCR1 and -opioid receptors were coexpressed on the same neuronal cells.…”

Modulation of Peripheral Sensory Neurons by the Immune System: Implications for Pain Therapy

“…However, in mouse DRG neurons, ␦-receptors are the first to be expressed on embryonic day 12.5 (E12.5), followed by the -(E13.5) and -receptors (E17.5) (Zhu et al, 1998). In rat, a greater proportion of DRG neurons expressing -and ␦-receptors was found before postnatal day 7 (P7) than at P21 (-receptor was not examined) (Beland and Fitzgerald, 2001;Nandi et al, 2004). During the first postnatal week, both opioid receptors were detected in cells of all sizes, but by P21, expression was restricted to small-and medium-diameter cells, suggesting a selective down-regulation in nonnociceptive neurons (Beland and Fitzgerald, 2001;Nandi et al, 2004).…”

“…In rat, a greater proportion of DRG neurons expressing -and ␦-receptors was found before postnatal day 7 (P7) than at P21 (-receptor was not examined) (Beland and Fitzgerald, 2001;Nandi et al, 2004). During the first postnatal week, both opioid receptors were detected in cells of all sizes, but by P21, expression was restricted to small-and medium-diameter cells, suggesting a selective down-regulation in nonnociceptive neurons (Beland and Fitzgerald, 2001;Nandi et al, 2004). This notion was supported by another study examining -receptor mRNA and function (Wu et al, 2009).…”

A Novel Endocytic Recycling Signal That Distinguishes the Membrane Trafficking of Naturally Occurring Opioid Receptors

“…We have addressed these questions by focusing on the murine and ␦ opioid receptors (MOR and DOR, respectively), homologous G protein-coupled neuropeptide receptors that are natively co-expressed in several cell types (18 -20) yet differ significantly in membrane trafficking properties (21)(22)(23). Studies of cultured cells indicate that both MOR and DOR are rapidly endocytosed via clathrin-coated pits and colocalize in early endosomes within several minutes after agonist-induced activation.…”