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| Author(s): |
Carina Cicconi Paccola
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina Veterinária e Zootecnia (FMVZ/SBD) |
| Defense date: | 2008-02-13 |
| Examining board members: |
Renata Giorgi;
Marucia Chacur;
Paulo César Maiorka
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| Advisor: | Renata Giorgi |
| Abstract | |
The synthetic peptide identical to the C-terminus of murine S100A9 protein (mS100A9p) has antinociceptive effect on different acute inflammatory pain models. In this study, the effect of mS100A9p was evaluated on neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve in rats, and the possible mechanisms involved in this effect were investigated. Hyperalgesia, allodynia, and spontaneous pain were assessed to evaluate nociception. Rats were treated with different doses of mS100A9p by intraplantar, oral, or intrathecal routes on day 14 after CCI, and nociception was evaluated 1 hour later. These three routes of administration blocked hyperalgesia, allodynia and spontaneous pain. The duration of mS100A9p effect depends on the route used and the phenomenon analyzed. Moreover, intraplantar injection of mS100A9p in the contralateral paw inhibited the hyperalgesia and allodynia induced by CCI. When mS100A9p was administered by intraplantar route on day 7 after CCI, it reversed the inflammatory hyperalgesia observed in this period. The mechanisms likely involved in the antinociceptive effect of mS100A9p were investigated by administration of antagonists of serotonin, norepinephrine, GABA (A and B) and opioid receptors. Only the GABAB receptor antagonist completely reversed the antinociceptive effect of mS100A9p on neuropathic pain on day 14 after CCI. Besides, the expression of Egr-1, Fos and TNFα proteins was evaluated in the spinal cord of rats submitted to CCI and treated with mS100A9p on days 7 or 14 after CCI. The expression of Egr-1 and Fos was increased in animals not treated or treated with vehicle on days 7 and 14 after CCI. On the other hand, mS100A9p inhibited the expression of these two proteins in the dorsal horn of spinal cord ipsilateral to CCI. The increase in TNFα expression was observed exclusively on day 7 after CCI. In the same time period, mS100A9p nhibited the expression of TNFα in the ventral horn of spinal cord of animals submitted to CCI. The results obtained herein demonstrate that the C-terminus of murine S100A9 protein inhibits the experimental neuropathic pain by a GABAB-dependent action, suggesting that this peptide promotes the activation of spinal inhibitory mechanisms leading to the reduction of activation of spinal neurons. Therefore, mS100A9p demonstrates a potential therapeutic use in persistent pain syndromes. (AU) | |