Early life pain experience changes adult functional pain connectivity in the rat somatosensory and the medial prefrontal cortex

Abstract

Early life pain experience (ELP) alters adult pain behaviour and increases injury induced pain hypersensitivity, but the effect of ELP upon adult functional brain connectivity is not known. We have performed continuous local field potential (LFP) recording in the awake adult male rats to test the effect of ELP upon functional cortical connectivity related to pain behaviour. Somatosensory cortex (S1) and medial prefrontal cortex (mPFC) LFPs evoked by mechanical hindpaw stimulation were recorded simultaneously with pain reflex behaviour for 10 days after adult skin injury. We show that, post adult injury, S1 LFP delta and gamma energy and S1 LFP delta/gamma frequency modulation are significantly increased in ELP rats compared to controls. Adult injury also induces increases in S1-mPFC functional connectivity which is significantly prolonged in ELP rats, lasting 4 days compared to 1 day in controls. Importantly, the increases in LFP energy and connectivity in ELP rats were directly correlated with increased behavioural pain hypersensitivity. Thus, early life pain (ELP) alters adult brain functional connectivity, both within and between cortical areas involved in sensory and affective dimensions of pain. The results reveal altered brain connectivity as a mechanism underlying the effects of early life pain upon adult pain perception. Significance StatementPain and stress in early life has a lasting impact upon pain behaviour and may increase vulnerability to chronic pain in adults. Here we record pain-related cortical activity and simultaneous pain behaviour in awake adult male rats previously exposed to pain in early life. We show that functional connectivity within and between the somatosensory cortex and the medial prefrontal cortex is increased in these rats and that these increases are correlated with their behavioural pain hypersensitivity. The results reveal that early life pain alters adult brain connectivity, which may explain the impact of childhood pain upon adult chronic pain vulnerability.