Neonatal maternal separation stress alters neuropathic pain behaviour and spinal nociceptive processing in rats

Aims
Early life stress enhances vulnerability to metabolic and mental disorders in adulthood. Altered pain sensitivity and dysfunctional emotional processing have been described in this context. We assessed the impact of neonatal maternal separation (MS) on chronic constriction injury (CCI) induced neuropathic pain behavior and biochemical spinal processing in early adulthood.
Methods
Four groups of rats were tested: Controls, MS, CCI, MS+CCI. For MS, pups were separated from the dam from postnatal day 2 to 12 for 3 hours per day. At an age of 7 weeks mechanical and thermal pain thresholds where assessed by the von Frey and the cold plate test. CCI surgery was performed in two of the experimental groups and behavioural measurements were continued until day 21 post surgery. After decapitation spinal cord levels L4/L5 were removed and total RNA was extracted to perform qPCR.
Results
MS alone did not affect pain thresholds. Surprisingly, MS+CCI rats were less sensitive to mechanical and thermal stimuli compared to CCI. Regarding the biochemical data, MS as well as MS+CCI led to an upregulation of glial markers, cytokines and growth factors and to a downregulation of glutamate receptors and transporters.
Conclusion
Behavioral and biochemical data are conflicting. The reduced pain sensitivity in MS animals is in contrast to activation of glia and enhanced expression of cytokines but in line with reduced glutamatergic signalling.
Since MS and MS+CCI groups did not differ, pain-related processing may have been outweighed by stress-related programming of biochemical reactivity.