Centre d'Evaluation et de Traitement de la Douleur, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
Centre National de la Recherche Scientifique, Université de Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, Strasbourg, France.
Eur J Pain. 2022 Jan;26(1):43-60. doi: 10.1002/ejp.1846. Epub 2021 Aug 9.
Neuropathic pain arises as a direct consequence of a lesion or disease affecting the somatosensory system. A number of preclinical studies have provided evidence for the involvement of cytokines, predominantly secreted by a variety of immune cells and by glial cells from the nervous system, in neuropathic pain conditions. Clinical trials and the use of anti-cytokine drugs in different neuropathic aetiologies support the relevance of cytokines as treatment targets. However, the use of such drugs, in particularly biotherapies, can provoke notable adverse effects. Moreover, it is challenging to select one given cytokine as a target, among the various neuropathic pain conditions. It could thus be of interest to target other proteins, such as growth factors, in order to act more widely on the neuroinflammation network. Thus, platelet-rich plasma (PRP), an autologous blood concentrate, is known to contain a natural concentration of growth factors and immune system messengers and is widely used in the clinical setting for tissue regeneration and repair.
In the present review, we critically assess the current knowledge on cytokines in neuropathic pain by taking into consideration both human studies and animal models.
This analysis of the literature highlights the pathophysiological importance of cytokines. We particularly highlight the concept of time- and tissue-dependent cytokine activation during neuropathic pain conditions.
Thus, direct or indirect cytokines modulation with biotherapies or growth factors appears relevant. In addition, we discuss the therapeutic potential of localized injection of PRP as neuropathic pain treatment by pointing out the possible link between cytokines and the action of PRP.
Preclinical and clinical studies highlight the idea of a cytokine imbalance in the development and maintenance of neuropathic pain. Clinical trials with anticytokine drugs are encouraging but are limited by a 'cytokine candidate approach' and adverse effect of biotherapies. PRP, containing various growth factors, is a new therapeutic used in regenerative medicine. Growth factors can be also considered as modulators of cytokine balance. Here, we emphasize a potential therapeutic effect of PRP on cytokine imbalance in neuropathic pain. We also underline the clinical interest of the use of PRP, not only for its therapeutic effect but also for its safety of use.
神经病理性疼痛是由于躯体感觉系统的损伤或疾病直接引起的。许多临床前研究已经证明细胞因子的参与,这些细胞因子主要由各种免疫细胞和神经系统的神经胶质细胞分泌,与神经病理性疼痛状况有关。临床试验和在不同神经病理性病因中使用抗细胞因子药物支持细胞因子作为治疗靶点的相关性。然而,此类药物(特别是生物疗法)的使用会引起明显的不良反应。此外,在各种神经病理性疼痛情况下,选择一种特定的细胞因子作为靶点是具有挑战性的。因此,针对其他蛋白质(如生长因子)可能会更广泛地作用于神经炎症网络,从而引起关注。因此,富含血小板的血浆(PRP)是一种自体血液浓缩物,已知含有天然浓度的生长因子和免疫系统信使,并且广泛用于临床环境中的组织再生和修复。
在本综述中,我们通过考虑人类研究和动物模型,批判性地评估了细胞因子在神经病理性疼痛中的当前知识。
对文献的分析强调了细胞因子在病理生理学中的重要性。我们特别强调了在神经病理性疼痛情况下细胞因子激活的时间和组织依赖性概念。
因此,生物疗法或生长因子的直接或间接细胞因子调节似乎是相关的。此外,我们通过指出细胞因子与 PRP 作用之间的可能联系,讨论了局部注射 PRP 作为神经病理性疼痛治疗的治疗潜力。
临床前和临床研究强调了细胞因子失衡在神经病理性疼痛的发展和维持中的作用。抗细胞因子药物的临床试验令人鼓舞,但受到“细胞因子候选方法”和生物疗法不良反应的限制。富含各种生长因子的 PRP 是一种用于再生医学的新型治疗方法。生长因子也可以被认为是细胞因子平衡的调节剂。在这里,我们强调了 PRP 在神经病理性疼痛中细胞因子失衡的潜在治疗作用。我们还强调了 PRP 在临床应用中的兴趣,不仅因其治疗效果,还因其使用安全性。