Acute Pain and a Motivational Pathway in Adult Rats: Influence of Early Life Pain ExperienceReportar como inadecuado

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The importance of neonatal experience upon behaviour in later life is increasingly recognised. The overlap between pain and reward pathways led us to hypothesise that neonatal pain experience influences reward-related pathways and behaviours in adulthood.

Methodology-Principal Findings

Rat pups received repeat plantar skin incisions neonatal IN or control procedures neonatal anesthesia only, AN at postnatal days P3, 10 and 17. When adult, rats with neonatal ‘pain history’ showed greater sensory sensitivity than control rats following acute plantar skin incision. Motivational behaviour in the two groups of rats was tested in a novelty-induced hypophagia NIH paradigm. The sensitivity of this paradigm to pain-induced changes in motivational behaviour was shown by significant increases in the time spent in the central zone of the arena 43.7±5.9% vs. 22.5±6.7%, p<0.05, close to centrally placed food treats, and decreased number of rears 9.5±1.4 vs. 19.2±2.3, p<0.001 in rats with acute plantar skin incision compared to naive, uninjured animals. Rats with a neonatal ‘pain history’ showed the same pain-induced behaviour in the novelty-induced hypophagia paradigm as controls. However, differences were observed in reward-related neural activity between the two groups. Two hours after behavioural testing, brains were harvested and neuronal activity mapped using c-Fos expression in lateral hypothalamic orexin neurons, part of a specific reward seeking pathway. Pain-induced activity in orexin neurons of control rats 18.4±2.8% was the same as in uninjured naive animals 15.5±2.6%, but in those rats with a ‘pain history’, orexinergic activity was significantly increased 27.2±4.1%, p<0.01. Furthermore the extent of orexin neuron activation in individual rats with a ‘pain history’ was highly correlated with their motivational behaviour r = −0.86, p = 0.01.


These results show that acute pain alters motivational behaviour and that neonatal pain experience causes long-term changes in brain motivational orexinergic pathways, known to modulate mesolimbic dopaminergic reward circuitry.

Autor: Lucie A. Low , Maria Fitzgerald



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