Dos Reis Renata Cristiane, Kopruszinski Caroline Machado, Nones Carina Fernanda Mattedi, Aguiar Débora Assunção, Chichorro Juliana Geremias
Department of Pharmacology, Biological Sciences Sector, Federal University of Parana, Curitiba, PR, Brazil.
Behav Pharmacol. 2020 Feb;31(1):27-33. doi: 10.1097/FBP.0000000000000503.
It has been proposed that neurotrophin-3 acts in a manner that is opposed to nerve growth factor, especially in the modulation of heat hyperalgesia. Injury to the constriction of the infraorbital nerve (CION) is a well-established model of trigeminal neuropathic pain that leads to robust heat, cold, and mechanical hyperalgesia. Here, we assessed the effect of local neurotrophin-3 treatment on CION-induced hyperalgesia, and we examined some mechanisms related to the effect of neurotrophin-3. Neurotrophin-3 (1 µg/50 µl) injected into the upper lip of CION rats caused a significant and long-lasting reduction of CION-induced heat hyperalgesia, but failed to affect cold and mechanical hyperalgesia. Increased levels of neurotrophin-3 were detected in the injured nerve at the time point that represents the peak of heat hyperalgesia. The anti-hyperalgesic effect of neurotrophin-3 was markedly reduced in the presence of an antagonist of TrkA receptors (K-252a, 1 μg/50 μl). Moreover, association of lower doses of neurotrophin-3 with an antibody anti-nerve growth factor resulted in a synergistic anti-hyperalgesic effect in CION rats. Local injection of nerve growth factor (3 µg/50 µl) or the TRPV1 agonist capsaicin (1 μg/50 μl), but not neurotrophin-3 injection (1 µg/50 µl), resulted in long-lasting facial heat hyperalgesia, which was both significantly reduced by previous neurotrophin-3 local treatment. In conclusion, we suggest that neurotrophin-3 is a potent modulator of facial heat hyperalgesia, which may exert an inhibitory influence on the trkA pathway. Neurotrophin-3 treatment may represent a promising approach, especially in pain conditions associated with increased levels of nerve growth factor.
有人提出，神经营养因子-3的作用方式与神经生长因子相反，尤其是在热痛觉过敏的调节方面。眶下神经缩窄损伤（CION）是一种公认的三叉神经病理性疼痛模型，可导致强烈的热、冷和机械性痛觉过敏。在此，我们评估了局部给予神经营养因子-3对CION诱导的痛觉过敏的影响，并研究了与神经营养因子-3作用相关的一些机制。向CION大鼠的上唇注射神经营养因子-3（1μg/50μl）可显著且持久地减轻CION诱导的热痛觉过敏，但对冷痛觉过敏和机械性痛觉过敏无影响。在代表热痛觉过敏峰值的时间点，损伤神经中检测到神经营养因子-3水平升高。在存在TrkA受体拮抗剂（K-252a，1μg/50μl）的情况下，神经营养因子-3的抗痛觉过敏作用明显减弱。此外，较低剂量的神经营养因子-3与抗神经生长因子抗体联合使用，在CION大鼠中产生了协同抗痛觉过敏作用。局部注射神经生长因子（3μg/50μl）或TRPV1激动剂辣椒素（1μg/50μl），但不是注射神经营养因子-3（1μg/50μl），会导致持久的面部热痛觉过敏，而先前的神经营养因子-3局部治疗可显著减轻这种过敏。总之，我们认为神经营养因子-3是面部热痛觉过敏的有效调节剂，可能对trkA通路产生抑制作用。神经营养因子-3治疗可能是一种有前景的方法，尤其是在与神经生长因子水平升高相关的疼痛状况中。
