The emergence of adolescent onset pain hypersensitivity following neonatal nerve injury.
The emergence of adolescent onset pain hypersensitivity following neonatal nerve injury.
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DOI：
10.1186/1744-8069-8-30
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发表时间：
2012-04-24
期刊：
影响因子：
3.3
通讯作者：
Fitzgerald M
中科院分区：
文献类型：
--
作者：
Vega-Avelaira D;McKelvey R;Hathway G;Fitzgerald M
周围神经损伤可在成人中引发神经性疼痛，但在婴儿期或幼儿期持续时几乎不引起疼痛。这在新生儿神经损伤不引起疼痛行为的啮齿动物模型中得到证实。然而，延迟性疼痛可以在神经损伤后相当长的一段时间内出现，为了检查这种早期神经损伤，我们对大鼠疼痛行为进行了长期随访，直到青春期和成年期。对10日龄（P10）大鼠幼仔进行坐骨神经损伤（SNI）或假手术，并在术后3、7、14、21、28、38和44天分析机械伤害性反射阈值。虽然在P10手术后的前2-3周，同侧的机械阈值与对照组没有显著差异，但在该时间段之后，从手术后21天（P31）开始，SNI组在早期神经损伤后与其他组相比发生了显著的超敏反应。术后21天，同侧机械伤害性阈值比对侧和假手术阈值低2倍（SNI-同侧28（±5）g对照组69（±9）g，p < 0.001，3因素ANOVA，n = 6/组）。重要的是，未观察到对热阈值的影响。这种超敏性伴随着DRG和背角中的巨噬细胞、小胶质细胞和星形胶质细胞的活化，但背角p38或JNK表达没有显著变化。预先给予米诺环素（每日40 mg/kg，s.c.）不能阻止该效应。另一方面，氯胺酮（20 mg/kg，s.c.）对神经损伤同侧的机械伤害性阈值产生剂量依赖性逆转，使得阈值在最高剂量20 mg/Kg时恢复至对照水平。我们报告了一个新的后果，早期生活神经损伤，机械过敏只出现在以后的生活。这种延迟的青少年机械痛阈发作伴随着神经免疫激活和脊髓伤害性回路的NMDA依赖性中枢敏化。机械疼痛敏感性的延迟发作可能为理解早期损伤的长期影响提供线索，例如迟发性幻痛和复杂的青少年慢性疼痛综合征的出现。
Peripheral nerve injuries can trigger neuropathic pain in adults but cause little or no pain when they are sustained in infancy or early childhood. This is confirmed in rodent models where neonatal nerve injury causes no pain behaviour. However, delayed pain can arise in man some considerable time after nerve damage and to examine this following early life nerve injury we have carried out a longer term follow up of rat pain behaviour into adolescence and adulthood. Spared nerve injury (SNI) or sham surgery was performed on 10 day old (P10) rat pups and mechanical nociceptive reflex thresholds were analysed 3, 7, 14, 21, 28, 38 and 44 days post surgery. While mechanical thresholds on the ipsilateral side are not significantly different from controls for the first 2–3 weeks post P10 surgery, after that time period, beginning at 21 days post surgery (P31), the SNI group developed following early life nerve injury significant hypersensitivity compared to the other groups. Ipsilateral mechanical nociceptive threshold was 2-fold below that of the contralateral and sham thresholds at 21 days post surgery (SNI-ipsilateral 28 (±5) g control groups 69 (±9) g, p < 0.001, 3-way ANOVA, n = 6 per group). Importantly, no effect was observed on thermal thresholds. This hypersensivity was accompanied by macrophage, microglial and astrocyte activation in the DRG and dorsal horn, but no significant change in dorsal horn p38 or JNK expression. Preemptive minocycline (daily 40 mg/kg, s.c) did not prevent the effect. Ketamine (20 mg/kg, s.c), on the other hand, produced a dose-dependent reversal of mechanical nociceptive thresholds ipsilateral to the nerve injury such that thresholds return to control levels at the highest doses of 20 mg/Kg. We report a novel consequence of early life nerve injury whereby mechanical hypersensitivity only emerges later in life. This delayed adolescent onset in mechanical pain thresholds is accompanied by neuroimmune activation and NMDA dependent central sensitization of spinal nociceptive circuits. This delayed onset in mechanical pain sensitivity may provide clues to understand the long term effects of early injury such as late onset phantom pain and the emergence of complex adolescent chronic pain syndromes.
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影响因子：
5
作者：
Fadel, S;Sarzotti, M
通讯作者：
Sarzotti, M
影响因子：
2
作者：
Huang, Han-Wei;Wang, Wen-Chi;Lin, Chou-Ching K.
通讯作者：
Lin, Chou-Ching K.
DOI：
10.1523/jneurosci.4569-09.2009
发表时间：
2009-11-18
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Costigan M;Moss A;Latremoliere A;Johnston C;Verma-Gandhu M;Herbert TA;Barrett L;Brenner GJ;Vardeh D;Woolf CJ;Fitzgerald M
通讯作者：
Fitzgerald M
影响因子：
7.4
作者：
Gao, X;Kim, HK;Chung, K
通讯作者：
Chung, K
影响因子：
7.4
作者：
Bourquin, Anne-Frederique;Sueveges, Maria;Decosterd, Isabelle
通讯作者：
Decosterd, Isabelle