Toward a central origin of nociceptive hypersensitivity in adult rats
after a neonatal maternal separation
Abstract
Early life adversities alter the development of a still maturing nervous
system and can have long-term consequences on its function at adult age.
This include nociceptive circuits that are critical to shape an adaptive
pain response to protect our organism from potentially damaging insults.
As such, adult rats with a history of neonatal maternal separation (NMS)
display a visceral and somatic nociceptive hypersensitivity and
inefficient analgesic responses to stress. In this study, we have
characterized the consequences of NMS on wide dynamic range neurons
(WDR) in the spinal cord of anesthetized adult rat during the
nociceptive processing of hot and cold noxious information. We found
that WDR neurons of NMS rats display an excessive coding of mechanical
and thermal information applied at the rat hindpaws. This nicely
explains the hypernociceptive behaviors seen after noxious mechanical,
cold and hot peripheral stimulation. A peripheral change in the
expression of molecular transducers for these stimuli (i.e. TRPV1,
TRPM8, TRPA1) does not seem to account for this general
hyperexcitability. Instead, a decreased chloride-mediated inhibitory
tone on WDR neurons may play a role as indicated by the abnormal
elevated of the type 1 Na-K-Cl cotransporter transcripts. Altogether, we
propose that long-term consequences of NMS is associated with a reduced
spinal cord inhibition favoring the expression of pain hypersensitivity.
We cannot exclude that this phenomenon is also present at supraspinal
sites as other NMS-associated symptoms include also excessive anxiety
and impaired sociability.