Improving analgesia and minimising the impact of surgery in early life

Supervisors: Dr Suellen Walker

Peri-operative care and effective analgesia is essential to reduce distress and minimize the impact of surgery. The developing nervous system is especially vulnerable to alterations in sensory experience and responses to injury and anaesthesia/analgesia can vary significantly from those at older ages [1,2]. While the beneficial impact of adequate neonatal anaesthesia and analgesia on acute peri-operative morbidity has been long recognized, pain and injury in early life can also produce adverse long-term alterations in the developing nervous system [1] including persistent alterations in sensory processing and future pain sensitivity [3].

Plantar hindpaw incision is a model of surgical injury that produces quantifiable hyperalgesia at all postnatal ages [4]. Incision in the first postnatal week, but not at older ages, is associated with increased hyperalgesia following a repeat incision. This effect is both dependent on primary afferent activity at the time of initial injury [4] and associated with an enhanced neuroimmune response in the spinal dorsal horn in adulthood [5].

Using established methods in the postnatal rat, this proposal aims to evaluate the ability of mechanistically different analgesics to modulate both the acute and long-term impact of neonatal surgery. Techniques will include behavioural and electrophysiological measures of spinal reflex sensitivity and analysis of spinal cord tissue with immunohistochemistry, and is suited to students with a background in neuroscience or pharmacology.

References:
1) Fitzgerald M, Walker SM: Infant pain management: a developmental neurobiological approach. Nat Clin Pract Neurol 2009; 5: 35 -50
2) Walker SM, Yaksh TL: Neuraxial analgesia in neonates and infants: a review of clinical and preclinical strategies for the development of safety and efficacy data. Anesth Analg 2012; 115: 638-62
3) Walker SM, Franck LS, Fitzgerald M, Myles J, Stocks J, Marlow N: Long-term impact of neonatal intensive care and surgery on somatosensory perception in children born extremely preterm. Pain 2009; 141: 79 -87
4) Walker SM, Tochiki KK, Fitzgerald M: Hindpaw incision in early life increases the hyperalgesic response to repeat surgical injury: critical period and dependence on initial afferent activity. Pain 2009; 147: 99-106
5) Beggs S, Currie G, Salter MW, Fitzgerald M, Walker SM: Priming of adult pain responses by neonatal pain experience: maintenance by central neuroimmune activity. Brain 2012; 135: 404-17