Department of Physiology and Pharmacology, University of Calgary, 3330 Hospital Drive NW, Calgary, Canada.
J Pharm Pharm Sci. 2013;16(2):313-20. doi: 10.18433/j3w02s.
Pediatric spinal cord injury (SCI) often leads to increased nociceptive input resulting in aberrant motor output like tremor and spasticity. Acute plasticity within spinal pain and motor networks following pediatric SCI may result in long-term sensorimotor disabilities. Despite this, pediatric SCI remains poorly understood. Part of the problem lies in the paucity of detailed studies aimed at defining sensorimotor control by nociceptors during development. This review provides an overview of work that highlights afferent control of sensorimotor networks by defined nociceptors in the developing spinal cord. Here, we focus on the well established and widely used neonatal sensorimotor model called sacrocaudal afferent (SCA) pathway. Until recently, the identity of specific subclasses of nociceptive afferents in the SCA pathway controlling developing sensorimotor networks was unknown. We highlight here the use of members of the Transient Receptor Potential (TRP) ion channels and mouse genetics to identify specific subsets of nociceptive afferents in the SCA pathway. In addition, we highlight the use of mouse genetics to map sensorimotor networks during development and potential future applications. A neonatal spinal cord model of central neuropathic pain via a defined set of nociceptors is presented as a probe into potential therapeutic avenues in neonatal SCI. Finally, knowledge translation from neonatal basic research to the pediatric population in the clinic is described. In conclusion, studies in neonatal models may lead to therapeutic strategies and pharmaceuticals for chronic pain and motor dysfunction after SCI during development.
儿科脊髓损伤 (SCI) 常导致伤害性传入增加,从而导致异常的运动输出,如震颤和痉挛。儿科 SCI 后脊髓疼痛和运动网络的急性可塑性可能导致长期感觉运动功能障碍。尽管如此,儿科 SCI 仍未得到充分理解。部分问题在于缺乏旨在定义发育过程中伤害感受器对感觉运动控制的详细研究。这篇综述概述了强调发育中脊髓中特定伤害感受器对感觉运动网络传入控制的工作。在这里,我们专注于已建立且广泛使用的称为骶尾传入 (SCA) 途径的新生儿感觉运动模型。直到最近,控制发育中感觉运动网络的 SCA 途径中特定伤害性传入的特定子类的身份仍然未知。我们在这里强调使用瞬时受体电位 (TRP) 离子通道和小鼠遗传学来鉴定 SCA 途径中特定的伤害性传入子集。此外,我们强调使用小鼠遗传学来映射发育过程中的感觉运动网络及其潜在的未来应用。通过一组特定的伤害感受器,提出了一种新生儿中枢性神经病理性疼痛的脊髓模型,作为探索新生儿 SCI 中潜在治疗途径的探针。最后,描述了从新生儿基础研究到临床儿科人群的知识转化。总之,新生儿模型的研究可能会为发育过程中 SCI 后慢性疼痛和运动功能障碍的治疗策略和药物治疗提供依据。