Minocycline attenuates mechanical allodynia and expression of spinal NMDA receptor 1 subunit in rat neuropathic pain mod
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ORIGINAL PAPER
Minocycline attenuates mechanical allodynia and expression of spinal NMDA receptor 1 subunit in rat neuropathic pain model Shaofeng Pu & Yongming Xu & Dongping Du & Meirong Yang & Xin Zhang & Junzhen Wu & Wei Jiang
Received: 14 November 2011 / Accepted: 17 October 2012 / Published online: 1 November 2012 # University of Navarra 2012
Abstract Recent studies have indicated that minocycline, a microglia inhibitor, could potentially be used as an antinociceptive agent in pain management, although the underlying mechanisms remain elusive. In this study, we investigated the extent to which minocycline could influence pain behavior in association with the expression of the N-methyl-D-aspartic acid receptor 1 (NMDAR1) in a rat L5 spinal nerve ligation (SNL) model. We observed that the intrathecal injection of minocycline significantly attenuated mechanical allodynia in a rat SNL model from day 1 postinjection and persisted for at least 18 days. We also observed that the expression of NMDAR1 was increased in the spinal dorsal horn at 8 days after SNL, which could be partly inhibited through the intrathecal injection of minocycline. These findings suggest that the attenuation of allodynia in the SNL model following minocycline administration might be associated with the inhibited expression of NMDAR1 and, therefore, might play an important role in the minocycline-mediated antinociception. Shaofeng Pu and Yongming Xu contributed equally to this work. S. Pu : Y. Xu : D. Du (*) : M. Yang : X. Zhang : J. Wu : W. Jiang Pain Management Center, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, 600 Yi Shan Road, Shanghai 200233, People’s Republic of China e-mail: [email protected]
Keywords Minocycline . NMDA receptor . Mechanical allodynia . Neuropathic pain
Introduction Neuropathic pain is often involved in disorders, such as trigeminal neuralgia [8], postherpetic neuralgia, and diabetic peripheral neuropathy [30]. It is characterized by spontaneous pain, hyperalgesia, and allodynia, which can persist long-term, even after the initial injury has healed. These symptoms are related to peripheral and central sensitization mechanisms. Little is known about the mechanisms underlying the development and maintenance of neuropathic pain, and therefore, most treatments show little or no effectiveness [27]. Minocycline, also known as minocycline hydrochloride, is widely used as a broad-spectrum tetracycline antibiotic. Recently, researchers have become increasingly interested in the potential neuroprotective and anti-inflammatory effects of minocycline against neurodegenerative disorders, including amyotrophic lateral sclerosis [15], Huntington’s disease [5], and Parkinson’s disease [13]. Studies using rat models of pain facilitation have shown that minocycline attenuates mechanical allodynia and proinflammatory cytokine expression [21]. It has been suggested that minocycline exerts antinociceptive effects independent of its anti-inflammatory properties [36].
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Recent studies have shown that the activatio
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