Review

Preclinical Studies of Pediatric Pain: Functional Modulation of Spinal Pain Circuitry by Early Life Tissue Injury

Jie Li , Mark L. Baccei
Pain Research Center, Department of Anesthesiology, University of Cincinnati Medical Center, Cincinnati, OH, USA
J Anesth Perioper Med 2018; 5(6): 316- 324 . Published on Nov 28, 2018 . doi:10.24015/JAPM.2018.0111
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Abstract

Aim of review: Incomplete knowledge regarding the biological basis of pediatric pain has prompted the need for more research into how tissue injury during early life evokes hyperalgesia in infants, and the degree to which neonatal insults can alter nociceptive processing throughout development. This paper mainly reviews preclinical studies investigating the short- and long-term modifications of spinal nociceptive circuitry evoked by neonatal tissue damage. A better understanding of the plasticity resulting from neonatal injury may ultimately guide new clinical strategies to relieve pain in infants and children.
 
Methods: We conducted a review of recent clinical and preclinical publications relating to pediatric pain, with a focus on neuronal networks in the superficial dorsal horn (SDH) of the spinal cord that are directly innervated by primary sensory inputs and serve as a main site for the integration and transmission of nociceptive signals within the central nervous system (CNS).
 
Recent findings: Aberrant peripheral input following neonatal tissue damage produces a selective and transient enhancement in excitatory synaptic transmission in the SDH during early postnatal development. In addition, deficits in glycinergic inhibition were observed that persisted into adulthood, suggesting prolonged alterations in synaptic function within spinal pain circuits in response to neonatal tissue injury. As a result of a disrupted balance of inhibition vs. excitation onto mature lamina I projection neurons ascending to the parabrachial nucleus, neonatal tissue damage also produced a greater signaling “gain” in this population, as evidenced by more action potential discharge in response to primary afferent stimulation. Furthermore, tissue injury during the early life created a more permissive environment for spike timing-dependent long-term potentiation (t-LTP) to occur at sensory synapses onto mature projection neurons, thus allowing the repetitive activation of more weakly correlated sensory inputs and postsynaptic activity to produce LTP.  This provides a novel potential mechanism that ascending nociceptive signals could be amplified within the spinal cord.
  
Summary: The development of spinal pain circuits is subject to modifications by aberrant peripheral inputs that accompany tissue insults. Tissue injury during early life can lead to profound alterations in synaptic function in the SDH, such as an increased gain of projection neurons and facilitated LTP at sensory synapses onto these output neurons of the spinal pain circuit. Therefore, more effort is needed to further illustrate the consequences of neonatal tissue injury for the maturation of nociceptive pathways, with the ultimate goal of providing more age-appropriate clinical strategies to minimize the long-term impact of these injuries on the developing CNS. (Funded by the National Institutes of Health.)  
 
 
 
 
Citation: Jie Li, Mark L. Baccei. Preclinical Studies of Pediatric Pain: Functional Modulation of Spinal Pain Circuitry by Early Life Tissue Injury. J Anesth Perioper Med 2018;5:316-324. doi10.24015/JAPM.2018.0111
 
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