The consequences of pain in early life: injury-induced plasticity in developing pain pathways.
Bottom Line: Pain in infancy influences pain reactivity in later life, but how and why this occurs is poorly understood.Here we review the evidence for developmental plasticity of nociceptive pathways in animal models and discuss the peripheral and central mechanisms that underlie this plasticity.Finally, it is proposed that the endocannabinoid system deserves further attention in the search for mechanisms underlying injury-induced changes in pain processing in infants and children.
Affiliation: Department of Neuroscience, Physiology & Pharmacology, University College London, London, UK.Show MeSH
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Mentions: A common feature of these models is that a tissue injury at a critical period of development has long-term effects, outlasting the injury itself, resulting in adults with altered pain sensitivity compared with controls (Fig.1). The difference in pain sensitivity is assessed when the animals are adults as (1) changes in baseline sensory and nociceptive sensitivity as compared with controls (handled in exactly the same way as neonates but with no injury) and (2) changes in pain sensitivity (hyperalgesia) to re-injury as adults, compared with controls (adults receiving their first injury). This approach reveals a dual long-term effect of mild injury to the hindpaw (CAR inflammation or surgical incision) administered in the first 7–10 days of life. Mild injuries are associated with a widespread whole body baseline depression in sensory and nociceptive thresholds, or hyposensitivity, that emerges only when the rat is adolescent, i.e. 4–5 weeks old (Ren et al., 2004; Sternberg et al., 2005; Laprairie & Murphy, 2009). However, the area in and around the site of the neonatal injury retains an enhanced sensitivity to pain, so that a new injury applied to the region results in enhanced hyperalgesia that is greater in amplitude and more prolonged than controls (Ren et al., 2004; Chu et al., 2007; Walker et al., 2009b; Beggs et al., 2012b). The enhanced pain sensitivity can be observed within days of the first injury, but importantly is also present in the adult, long after the original neonatal injury has resolved. Neither the basal hyposensitivity nor the enhanced re-injury-associated hyperalgesia subside with age and are still evident in 120–125-day-old rats (Ren et al., 2004). Importantly, none of these effects occurs if the early inflammation or skin incision is administered after the first 7–10 days of life (Fig.2).
Affiliation: Department of Neuroscience, Physiology & Pharmacology, University College London, London, UK.