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Int. J. Mol. Sci. 2017, 18(10), 2143; https://doi.org/10.3390/ijms18102143

Single Administration of Melatonin Modulates the Nitroxidergic System at the Peripheral Level and Reduces Thermal Nociceptive Hypersensitivity in Neuropathic Rats

1
Department of Clinical and Experimental Sciences, Division of Anatomy and Physiopathology, University of Brescia, Viale Europa 11, 25123 Brescia, Italy
2
Interdipartimental University Center of Research “Adaption and Regeneration of Tissues and Organs—(ARTO)”, University of Brescia, Viale Europa 11, 25123 Brescia, Italy
3
Department of Cell Systems and Anatomy, The University of Texas Health Science Center, San Antonio, TX 78229, USA
*
Author to whom correspondence should be addressed.
Received: 15 September 2017 / Revised: 5 October 2017 / Accepted: 12 October 2017 / Published: 14 October 2017
(This article belongs to the Special Issue Melatonin and Its Analogues: Experimental and Clinical Aspects)
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Abstract

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. View Full-Text
Keywords: melatonin; neuropathic pain; rats; nitroxidergic system; skin; dorsal root ganglia melatonin; neuropathic pain; rats; nitroxidergic system; skin; dorsal root ganglia
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Borsani, E.; Buffoli, B.; Bonazza, V.; Reiter, R.J.; Rezzani, R.; Rodella, L.F. Single Administration of Melatonin Modulates the Nitroxidergic System at the Peripheral Level and Reduces Thermal Nociceptive Hypersensitivity in Neuropathic Rats. Int. J. Mol. Sci. 2017, 18, 2143.

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