Towards a central origin of nociceptive hypersensitivity in adult rats after a neonatal maternal separation

Early life adversities influence a nervous system still in development with long-term consequences for later life. These include nociceptive circuit alterations critical to shape an adaptive pain response to protect the organism from potential damage. Adult rats with a history of neonatal maternal separation (NMS) display 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 anaesthetized adult rats 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's hindpaws. This nicely explains the hypernociceptive behaviours 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 and 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 elevation of the type 1 Na-K-Cl cotransporter transcripts. Altogether, we propose that long-term consequences of NMS are associated with reduced spinal cord inhibition favouring the expression of pain hypersensitivity. We cannot exclude that this phenomenon is also present at supraspinal sites, as other NMS-associated symptoms include excessive anxiety and impaired sociability. Neonatal maternal separation is associated with pain hypersensitivity in adulthood, in addition to excessive anxiety, abnormal response to stress, and cognitive dysfunction. Among the many dysregulated gene products observed after these early life adverse events, expression of chloride transporters that optimize spinal inhibition is permanently altered. We hypothesized that spinal disinhibition mediated by chloride-mediated ionic channels such as GABAA and glycine receptors is responsible for the hyperexcitability observed in adult 'wide dynamic range' spinal neurons.image

Automated summary

Early life adversities can have long-term consequences on the developing nervous system, leading to altered pain processing. This study focuses on the effects of neonatal maternal separation on spinal cord neurons, finding that these neurons exhibit an excessive response to mechanical and thermal stimuli. The reduced inhibitory tone on these neurons may contribute to the observed pain hypersensitivity.