Nynke van den Hoogen1, Jacob Patijn1, Dick Tibboel1, Maria Fitzgerald2, Bert Joosten1, Charlie Kwok3
1) Netherlands 2) United Kingdom 3) Canada
In the Neonatal intensive care unit (NICU), new-born babies routinely undergo painful procedures, approximately 10-14 times per day. Clinical and experimental data suggests that noxious stimulation at critical stages of development has long-term consequences on nociceptive processing in later life. Here we use an experimental model of repeated procedural pain, closely mimicking the repetitive insults experienced in the NICU, to elucidate the long-term consequences of repetitive needle pricking in neonatal rats upon the activity of spinal nociceptive circuits. Neonatal rats received four needle pricks per day in the left hind-paw from postnatal day 0 to 7 as a model of procedural pain in infancy (n=13). Control pups were handled in the same way but did not receive pricks (n=11), or were left undisturbed (n=17). At the age of 8 weeks, animals received an ipsilateral hind-paw incision as a model of post-operative pain in adulthood. The effect of neonatal injury on adult pain sensitivity was quantified by in vivo measurements of excitability of spinal cord dorsal horn neurons in extracellular single unit recordings. Under isoflurane anaesthesia, wide dynamic range neurons (n=206) with a receptive field in the plantar surface of the ipsilateral hind paw were recorded in the lumbar dorsal horn. Spike activity was evoked using different modalities of cutaneous stimulation: touch, pinch and Von Frey filaments. Spinal cord dorsal horn neurons of adult rats that had undergone neonatal needle prick displayed increased responses to touch and noxious stimuli and enlarged receptive field areas compared to controls. Following paw incision in adulthood, enhanced responses were observed for only 5 days. This data shows that repeated procedural pain during early life primes spinal nociceptive circuits and results in enhanced signalling of both touch and pain in the adult spinal dorsal horn.
