Early Life Pain Experience Changes Adult Functional Pain Connectivity in the Rat Somatosensory and the Medial Prefrontal Cortex

Abstract

Early life pain (ELP) experience alters adult pain behavior and increases injury-induced pain hypersensitivity, but the effect of ELP on 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 on functional cortical connectivity related to pain behavior. Primary somatosensory cortex (S1) and medial prefrontal cortex (mPFC) LFPs evoked by mechanical hindpaw stimulation were recorded simultaneously with pain reflex behavior for 10 d after adult incision injury. We show that, after adult injury, sensory evoked S1 LFP δ and γ energy and S1 LFP δ/γ frequency coupling are significantly increased in ELP rats compared with controls. Adult injury also induces increases in S1-mPFC functional connectivity, but this is significantly prolonged in ELP rats, lasting 4 d compared with 1 d in controls. Importantly, the increases in LFP energy and connectivity in ELP rats were directly correlated with increased behavioral pain hypersensitivity. Thus, 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 ELP on adult pain perception.SIGNIFICANCE STATEMENTPain and stress in early life has a lasting impact on pain behavior and may increase vulnerability to chronic pain in adults. Here, we record pain-related cortical activity and simultaneous pain behavior 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 (mPFC) is increased in these rats and that these increases are correlated with their behavioral pain hypersensitivity. The results reveal that early life pain (ELP) alters adult brain connectivity, which may explain the impact of childhood pain on adult chronic pain vulnerability.