Minocycline and fluorocitrate suppress spinal nociceptive signaling in intrathecal IL‐1β–induced thermal hyperalgesic rats |
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Authors: | Chun‐Sung Sung Chen‐Hwan Cherng Zhi‐Hong Wen Wen‐Kuei Chang Shi‐Ying Huang Shinn‐Long Lin Kwok‐Hon Chan Chih‐Shung Wong |
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Affiliation: | 1. Department of Anesthesiology, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China;2. School of Medicine, National Yang‐Ming University, Taipei, Taiwan, Republic of China;3. Department of Anesthesiology, Tri‐Service General Hospital and National Defense Medical Center, Taipei, Taiwan, Republic of China;4. Department of Marine Biotechnology and Resources, Asia‐Pacific Ocean Research Center, National Sun Yat‐Sen University, Kaohsiung, Taiwan, Republic of China;5. Department of Anesthesiology, Cathay General Hospital, Taipei, Taiwan, Republic of China |
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Abstract: | We previously demonstrated that intrathecal IL‐1β caused thermal hyperalgesia in rats. This study was conducted to examine the effects and cellular mechanisms of glial inhibitors on IL‐1β–induced nociception in rats. The effects of minocycline (20 μg), fluorocitrate (1 nmol), and SB203580 (5 μg) on IL‐1β (100 ng) treatment in rats were measured by nociceptive behaviors, western blotting of p38 mitogen‐activated protein kinase (MAPK) and inducible nitric oxide synthase (iNOS) expression, cerebrospinal fluid nitric oxide (NO) levels, and immunohistochemical analyses. The results demonstrated that intrathecal IL‐1β activated microglia and astrocytes, but not neurons, in the dorsal horn of the lumbar spinal cord, as evidenced by morphological changes and increased immunoreactivity, phosphorylated p38 (P‐p38) MAPK, and iNOS expression; the activation of microglia and astrocytes peaked at 30 min and lasted for 6 h. The immunoreactivities of microglia and astrocytes were significantly increased at 30 min (6.6‐ and 2.7‐fold, respectively) and 6 h (3.3‐ and 4.0‐fold, respectively) following IL‐1β injection, as compared with saline controls at 30 min (all P < 0.01). IL‐1β induced P‐p38 MAPK and iNOS expression predominantly in microglia and less in astrocytes. Minocycline, fluorocitrate, or SB203580 pretreatment suppressed this IL‐1β–upregulated P‐p38 MAPK mainly in microglia and iNOS mainly in astrocytes; minocycline exhibited the most potent effect. Minocycline and fluorocitrate pretreatment abrogated IL‐1β–induced NO release and thermal hyperalgesia in rats. In conclusion, minocycline, fluorocitrate, and SB203580 effectively suppressed the IL‐1β–induced central sensitization and hyperalgesia in rats. © 2012 Wiley Periodicals, Inc. |
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Keywords: | interleukin‐1β spinal cord microglia astrocyte MAPK iNOS |
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