Department of Clinical and Experimental Sciences, Division of Anatomy and Physiopathology, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
Interdipartimental University Center of Research "Adaption and Regeneration of Tissues and Organs-(ARTO)", University of Brescia, Viale Europa 11, 25123 Brescia, Italy.
Int J Mol Sci. 2017 Oct 14;18(10):2143. doi: 10.3390/ijms18102143.
Neuropathic pain is a severe condition with unsatisfactory treatments. Melatonin, an indolamine, seems to be a promising molecule suitable for this purpose due to its well-known anti-inflammatory, analgesic, and antioxidant effects, as well as its modulation of the nitroxidergic system. Nevertheless, the data on its mechanism of action and potentialities are currently insufficient in this pathology, especially at the peripheral level. Thus, this work evaluated the effect of a single administration of melatonin in an established mononeuropathy pain model that monitors the behaviour and the changes in the nitroxidergic system in dorsal root ganglia and skin, which are affected by nervous impairment. Experiments were carried out on Sprague Dawley rats subdivided into the sham operated (control) and the chronic constriction injured animals, a model of peripheral neuropathic pain on sciatic nerve. Single administrations of melatonin (5-10 mg/kg) or vehicle were injected intraperitoneally on the 14th day after surgery, when the mononeuropathy was established. The animals were behaviourally tested for thermal hyperalgesia. The dorsal root ganglia and the plantar skin of the hind-paws were removed and processed for the immunohistochemical detection of neuronal and inducible nitric oxide synthases. The behavioural results showed an increase of withdrawal latency during the plantar test as early as 30 min after melatonin administration. The immunohistochemical results indicated a modulation of the nitroxidergic system both at dorsal root ganglia and skin level, permitting speculate on a possible mechanism of action. We showed that melatonin may be a possible therapeutic strategy in neuropathic pain.
神经性疼痛是一种治疗效果不佳的严重疾病。褪黑素作为一种吲哚胺，由于其具有抗炎、镇痛和抗氧化作用，以及对硝化系统的调节作用，似乎是一种很有前途的适用于该疾病的分子。然而，目前在这种病理状态下，褪黑素的作用机制及其潜在用途的数据还不够充分，尤其是在外周水平。因此，本研究在一种已建立的单神经病疼痛模型中评估了褪黑素单次给药的效果，该模型监测行为以及背根神经节和皮肤中硝化系统的变化，这些变化受神经损伤的影响。实验在 Sprague Dawley 大鼠中进行，分为假手术（对照组）和慢性缩窄性损伤动物组，后者是一种坐骨神经周围神经病疼痛模型。在手术后第 14 天，即单神经病建立后，通过腹腔内注射褪黑素（5-10mg/kg）或载体进行单次给药。对动物进行足底热痛觉过敏行为测试。取出背根神经节和后爪足底皮肤，进行神经元和诱导型一氧化氮合酶的免疫组织化学检测。行为学结果显示，在接受褪黑素给药后 30 分钟内，足底测试中的缩足潜伏期增加。免疫组织化学结果表明，硝化系统在背根神经节和皮肤水平都得到了调节，这使得人们可以推测其可能的作用机制。我们表明，褪黑素可能是治疗神经性疼痛的一种潜在策略。
