van den Hoogen N J, Tibboel D, Honig W M M, Hermes D, Patijn J, Joosten E A
Department of Anaesthesiology and Pain Management, Maastricht University Medical Centre, The Netherlands.
Department of Translational Neuroscience, School of Mental Health and Neuroscience, Maastricht University, The Netherlands.
Eur J Pain. 2016 Sep;20(8):1309-18. doi: 10.1002/ejp.855. Epub 2016 Feb 23.
Pain from skin penetrating procedures (procedural pain) during infancy in the neonatal intensive care unit (NICU) may result in changes of nociceptive sensitivity in later life. This supports the need for pain management during such vulnerable periods in life. This study, therefore, analyses the short- and long-term consequences of neonatal paracetamol (acetaminophen) treatment on pain behaviour in an experimental rat model of neonatal procedural pain.
A repetitive needle-prick model was used, in which neonatal rats received four needle pricks into the left hind paw per day from postnatal day 0 to day 7 (P0-P7). Paracetamol (50 mg/kg/day s.c.) was administered daily (P0-P7), and sensitivity to mechanical stimuli was compared with a needle-prick/saline-treated group and to a tactile control group. At 8 weeks of age, all animals underwent an ipsilateral paw-incision, modelling postoperative pain, and the duration of hypersensitivity was assessed.
Neonatal paracetamol administration had no effect upon short-term mechanical hypersensitivity during the first postnatal week or upon long-term baseline sensitivity from 3 to 8 weeks. However, neonatal paracetamol administration significantly reduced the postoperative mechanical hypersensitivity in young adults, caused by repetitive needle pricking.
Paracetamol administration during neonatal procedural pain does not alter short-term or long-term effects on mechanical sensitivity, but does reduce the duration of increased postoperative mechanical hypersensitivity in a clinically relevant neonatal procedural pain model.
Paracetamol can be used safely in neonatal rats. Neonatal paracetamol treatment had no effect upon short-term mechanical hypersensitivity during the first postnatal week, nor upon long-term baseline sensitivity from 3 to 8 weeks. Paracetamol treatment during the first postnatal week significantly reduced the postoperative mechanical hypersensitivity in young adult rats.
新生儿重症监护病房（NICU）中，婴儿期皮肤穿刺操作引起的疼痛（操作疼痛）可能会导致其日后生活中伤害性感受敏感性发生变化。这支持了在此类生命脆弱期进行疼痛管理的必要性。因此，本研究在新生大鼠操作疼痛的实验模型中，分析了新生儿对乙酰氨基酚（扑热息痛）治疗对疼痛行为的短期和长期影响。
采用重复针刺模型，新生大鼠从出生第0天至第7天（P0 - P7）每天接受4次左后爪针刺。每天给予对乙酰氨基酚（50 mg/kg/天，皮下注射）（P0 - P7），并将对机械刺激的敏感性与针刺/生理盐水处理组及触觉对照组进行比较。在8周龄时，所有动物均接受同侧爪切口手术，模拟术后疼痛，并评估超敏反应的持续时间。
新生儿期给予对乙酰氨基酚对出生后第一周的短期机械性超敏反应或3至8周的长期基线敏感性均无影响。然而，新生儿期给予对乙酰氨基酚可显著降低重复针刺引起的年轻成年大鼠术后机械性超敏反应。
在新生儿操作疼痛期间给予对乙酰氨基酚不会改变对机械敏感性的短期或长期影响，但在临床相关的新生儿操作疼痛模型中，确实可缩短术后机械性超敏反应增强的持续时间。
对乙酰氨基酚可在新生大鼠中安全使用。新生儿期给予对乙酰氨基酚对出生后第一周的短期机械性超敏反应及3至8周的长期基线敏感性均无影响。出生后第一周给予对乙酰氨基酚治疗可显著降低年轻成年大鼠术后机械性超敏反应。
