Surgical injury in the neonatal rat alters the adult pattern of descending modulation from the rostroventral medulla.
Surgical injury in the neonatal rat alters the adult pattern of descending modulation from the rostroventral medulla.
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DOI：
10.1097/aln.0000000000000658
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发表时间：
2015-06
期刊：
影响因子：
8.8
通讯作者：
Hathway GJ
中科院分区：
文献类型：
--
作者：
Walker SM;Fitzgerald M;Hathway GJ
新生儿疼痛和损伤可改变长期感觉阈值。下行前腹侧髓质（RVM）通路可以抑制或促进成人脊髓伤害感受加工。由于这些通路经历重要的出生后成熟，我们评估了新生儿手术损伤对RVM下行调节的长期影响。对出生后3天(P)麻醉的Sprague-Dawley大鼠进行足底后爪或前爪切口。对照组仅接受麻醉。测量后肢机械和热戒断阈值至6周龄（成人）。另外两组在切开坐骨神经前后分别给予布比卡因或生理盐水。采用股二头肌肌电图量化麻醉成年大鼠后肢痛觉反射敏感性，并测量RVM电刺激（5-200 μA）与基线相比的百分比变化。在先前有新生儿切口的成年大鼠（n=9）中，所有RVM刺激强度都降低了后肢反射敏感性，与对照组（n=5）的RVM刺激强度增加时典型的促进和抑制双峰模式形成对比（未受伤与新生儿切口，P<0.001）。新生儿对侧后爪或前爪的切开也导致所有刺激强度下后爪伤害性反射的RVM抑制。新生儿单侧切开后，双后肢行为力学阈值（平均±SEM， 28.1±8g比21.3±1.2g， P<0.001）和热潜伏期（7.1±0.4比5.3±0.3s， P<0.05）均增加。新生儿围手术期坐骨神经阻滞可防止损伤引起的RVM下降控制改变。新生儿手术损伤改变了RVM下降控制的产后发展，导致下降抑制占主导地位，基线反射敏感性普遍降低。局麻阻断预防突出了新生儿围手术期镇痛的重要性。
Neonatal pain and injury can alter long-term sensory thresholds. Descending rostroventral medulla (RVM) pathways can inhibit or facilitate spinal nociceptive processing in adulthood. As these pathways undergo significant postnatal maturation, we evaluated long-term effects of neonatal surgical injury on RVM descending modulation. Plantar hindpaw or forepaw incisions were performed in anesthetized postnatal day (P)3 Sprague-Dawley rats. Controls received anesthesia only. Hindlimb mechanical and thermal withdrawal thresholds were measured to 6 weeks of age (adult). Additional groups received pre- and post-incision sciatic nerve bupivacaine or saline. Hindpaw nociceptive reflex sensitivity was quantified in anesthetized adult rats using biceps femoris electromyography, and the effect of RVM electrical stimulation (5-200 μA) measured as percentage change from baseline. In adult rats with prior neonatal incision (n=9), all intensities of RVM stimulation decreased hindlimb reflex sensitivity, in contrast to the typical bimodal pattern of facilitation and inhibition with increasing RVM stimulus intensity in controls (n=5) (uninjured vs. neonatally-incised, P<0.001). Neonatal incision of the contralateral hindpaw or forepaw also resulted in RVM inhibition of hindpaw nociceptive reflexes at all stimulation intensities. Behavioral mechanical threshold (mean±SEM, 28.1±8g vs. 21.3±1.2g, P<0.001) and thermal latency (7.1±0.4 vs. 5.3±0.3s, P<0.05) were increased in both hindpaws following unilateral neonatal incision. Neonatal perioperative sciatic nerve blockade prevented injury-induced alterations in RVM descending control. Neonatal surgical injury alters the postnatal development of RVM descending control, resulting in a predominance of descending inhibition and generalized reduction in baseline reflex sensitivity. Prevention by local anesthetic blockade highlights the importance of neonatal perioperative analgesia.