Lucarini Elena, Micheli Laura, Martelli Alma, Testai Lara, Calderone Vincenzo, Ghelardini Carla, Di Cesare Mannelli Lorenzo
Pharmacology and Toxicology Section, Department of Neuroscience, Psychology, Drug Research, and Child Health (Neurofarba), University of Florence, Florence, Italy,
Department of Pharmacy, University of Pisa, Pisa, Italy.
J Pain Res. 2018 Nov 19;11:2905-2913. doi: 10.2147/JPR.S161882. eCollection 2018.
Current pharmacotherapy for persistent pain related to neuropathy or articular diseases is unsatisfactory, due to the large number of unresponsive patients and side effects. Isothiocyanates (ITCs) are a class of natural or synthetic compounds characterized by the general formula R-NCS. ITCs show antihyperalgesic effects in models of central and peripheral nervous tissue injury and anti-inflammatory properties. The pharmacodynamics are strictly related to the release of the gasotransmitter hydrogen sulfide (HS) from their moiety. In particular, phenyl ITC (PITC) and 3-carboxyphenyl ITC (3C-PITC) exhibit interesting slow HS-release properties suitable for treating painful pathology. The aim of the present work was to evaluate the efficacy of PITC and 3C-PITC against mechanical hyperalgesia and spontaneous pain induced by nerve injury and osteoarthritis.
Nerve injury and osteoarthritis were induced in rats by ligation of the sciatic nerve (chronic constriction injury) and intra-articular injection of monoiodoacetate, respectively. Behavioral tests were performed 14 days after damage induction.
Single subcutaneous administrations of PITC, 3C-PITC (4.43 and 13.31 µmol kg, respectively) were able to completely reverse hypersensitivity to noxious stimuli in both models of neuropathic and osteoarticular pain. The effect of ITCs was compared with that of NaHS, the prototypical HS donor, showing similar efficacy and higher potency. ITCs and NaHS also reduced spontaneous pain.
ITCs offer a promising novel approach to counteract persistent, drug-resistant painful pathology.
由于大量患者无反应以及存在副作用，目前用于治疗与神经病变或关节疾病相关的持续性疼痛的药物疗法并不令人满意。异硫氰酸酯（ITC）是一类通式为R-NCS的天然或合成化合物。ITC在中枢和外周神经组织损伤模型中显示出抗痛觉过敏作用以及抗炎特性。其药效学与从其部分释放气体递质硫化氢（HS）密切相关。特别是苯基异硫氰酸酯（PITC）和3-羧基苯基异硫氰酸酯（3C-PITC）表现出有趣的缓慢HS释放特性，适用于治疗疼痛性病理状况。本研究的目的是评估PITC和3C-PITC对神经损伤和骨关节炎诱导的机械性痛觉过敏和自发性疼痛的疗效。
分别通过结扎坐骨神经（慢性压迫性损伤）和关节内注射一碘乙酸在大鼠中诱导神经损伤和骨关节炎。在损伤诱导后14天进行行为测试。
单次皮下给予PITC、3C-PITC（分别为4.43和13.31 μmol/kg）能够完全逆转神经性和骨关节炎性疼痛两种模型中对有害刺激的超敏反应。将ITC的作用与典型的HS供体NaHS的作用进行比较，显示出相似的疗效和更高的效力。ITC和NaHS也减轻了自发性疼痛。
ITC为对抗持续性、耐药性疼痛性病理状况提供了一种有前景的新方法。
