Early life programming of pain: focus on neuroimmune to endocrine communication

Chronic pain constitutes a challenge for the scientific community and a significant economic and social cost for modern societies. Given the failure of current drugs to effectively treat chronic pain, which are based on suppressing aberrant neuronal excitability, we propose in this review an integrated approach that views pain not solely originating from neuronal activation but also the result of a complex interaction between the nervous, immune, and endocrine systems. Pain assessment must also extend beyond measures of behavioural responses to noxious stimuli to a more developmentally informed assessment given the significant plasticity of the nociceptive system during the neonatal period. Finally integrating the concept of perinatal programming into the pain management field is a necessary step to develop and target interventions to reduce the suffering associated with chronic pain. We present clinical and animal findings from our laboratory (and others) demonstrating the importance of the microbial and relational environment in programming pain responsiveness later in life via action on hypothalamo-pituitary adrenal (HPA) axis activity, peripheral and central immune system, spinal and supraspinal mechanisms, and the autonomic nervous system