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

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.