Cooper Andrew H, Hanmer Jenna M, Chapman Victoria, Hathway Gareth J
School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, United Kingdom. Dr. Cooper is now with the Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, United Kingdom.
Versus Arthritis Pain Centre, University of Nottingham, Nottingham, United Kingdom.
Pain Rep. 2020 Nov 27;5(6):e872. doi: 10.1097/PR9.0000000000000872. eCollection 2020 Nov-Dec.
Inflammation during the neonatal period can exacerbate pain severity following reinjury in adulthood. This is driven by alterations in the postnatal development of spinal and supraspinal nociceptive circuitry. However, the contribution of alterations in peripheral nociceptor function remains underexplored.
We examined whether neonatal complete Freund's adjuvant (CFA)-induced inflammation induced or altered adult development of hyperalgesic priming (inflammation-induced plasticity in nonpeptidergic C fibres) or altered postnatal reorganization of calcitonin gene-related peptide (CGRP)-expressing and isolectin B4 (IB4)-binding C fibres in the spinal dorsal horn (DH).
After intraplantar injection of CFA at postnatal day (P) 1, we assessed mechanical thresholds in adult (P60) rats before and after intraplantar carrageenan. One week later, intraplantar PGE-induced hypersensitivity persisting for 4 hours was deemed indicative of hyperalgesic priming. CGRP expression and IB4 binding were examined in adult rat DH after CFA.
P1 CFA did not alter baseline adult mechanical thresholds, nor did it change the extent or duration of carrageenan-induced hypersensitivity. However, this was slower to resolve in female than in male rats. Rats that previously received carrageenan but not saline were primed, but P1 hind paw CFA did not induce or alter hyperalgesic priming responses to PGE. In addition, CFA on P1 or P10 did not alter intensity or patterns of CGRP or IB4 staining in the adult DH.
Complete Freund's adjuvant-induced inflammation during a critical period of vulnerability to injury during early postnatal development does not induce or exacerbate hyperalgesic priming or alter the broad distribution of CGRP-expressing or IB4-binding afferent terminals in the adult dorsal horn.
新生儿期的炎症会加剧成年后再次受伤时的疼痛严重程度。这是由脊髓和脊髓上伤害性感受回路产后发育的改变所驱动的。然而，外周伤害感受器功能改变的作用仍未得到充分研究。
我们研究了新生儿期完全弗氏佐剂（CFA）诱导的炎症是否会诱导或改变成年期痛觉过敏启动（非肽能C纤维中的炎症诱导可塑性）的发展，或者改变脊髓背角（DH）中降钙素基因相关肽（CGRP）表达和异凝集素B4（IB4）结合C纤维的产后重组。
在出生后第1天（P1）足底注射CFA后，我们评估成年（P60）大鼠在足底注射角叉菜胶前后的机械阈值。一周后，足底注射前列腺素E（PGE）诱导的持续4小时的超敏反应被视为痛觉过敏启动的指标。在CFA处理后，检测成年大鼠DH中的CGRP表达和IB4结合情况。
P1期CFA并未改变成年大鼠的基线机械阈值，也未改变角叉菜胶诱导的超敏反应的程度或持续时间。然而，雌性大鼠的这种反应消退比雄性大鼠慢。先前接受角叉菜胶而非生理盐水注射的大鼠出现了启动现象，但P1期后爪CFA并未诱导或改变对PGE的痛觉过敏启动反应。此外，P1或P10期的CFA并未改变成年DH中CGRP或IB4染色的强度或模式。
在出生后早期发育中易受损伤的关键时期，完全弗氏佐剂诱导的炎症不会诱导或加剧痛觉过敏启动，也不会改变成年背角中表达CGRP或结合IB4的传入终末的广泛分布。
