Is functional state of spinal microglia involved in the anti-allodynic and anti-hyperalgesic effects of electroacupuncture in rat model of monoarthritis?

Sun, Shan; Mao-Ying, Qi-Liang; Cao, Hong; Li, Tingting; Han, Mei; Pan, Haili; Wang, Yanqing; Zhao, Zhi-Qi; Zhang, Yu‐Qiu

doi:10.1016/j.nbd.2007.02.007

Cited by 89 publications

(88 citation statements)

References 49 publications

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“…We herein showed for the first time that inhibition of CatB activity, either through genetic deletion or via a pharmacological inhibitor significantly reduced the CFA-induced long-lasting tactile allodynia without affecting the CFA-induced paw inflammation. In agreement with the significant reduction of CFA-induced pain hypersensitivity, the production of both mIL-1␤ and mIL-18 was significantly reduced in the spinal microglia of CatBϪ/Ϫ mice, indicating that inflammatory pain is dependent on the production of spinal mIL-1␤ and mIL-18, as has been suggested in previous studies (Guo et al, 2007;Shan et al, 2007;Verri et al, 2007;Fiorentino et al, 2008). Furthermore, a significant reduction of COX-2 was also observed in the spinal dorsal horn neurons of CFA-injected CatBϪ/Ϫ mice.…”

Section: Discussionsupporting

confidence: 89%

“…It has been considered that the microglial hyperactivation is involved in CFA-induced pain hypersensitivity, because treatment with minocycline completely prevented the development of CFA-induced allodynia (Shan et al, 2007). However, little information has been available about the endogenous activators of microglia in the spinal cord during inflammatory pain.…”

Section: Discussionmentioning

confidence: 99%

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Microglial Cathepsin B Contributes to the Initiation of Peripheral Inflammation-Induced Chronic Pain

Sun

Hayashi

et al. 2012

J. Neurosci.

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Interleukin (IL)-1␤ and IL-18 play critical roles in the induction of chronic pain hypersensitivity. Their inactive forms are activated by caspase-1. However, little is known about the mechanism underlying the activation of pro-caspase-1. There is increasing evidence that cathepsin B (CatB), a typical lysosomal cysteine protease, is involved in the pro-caspase-1 activation and the subsequent maturation of IL-1␤ and IL-18. In this context, CatB is considered to be an important molecular target to control chronic pain. However, no information is currently available about the role of CatB in chronic pain hypersensitivity. We herein show that CatB deficiency or the intrathecal administration of CA-074Me, a specific CatB inhibitor, significantly inhibited the induction of complete Freund's adjuvant-induced tactile allodynia in mice without affecting peripheral inflammation. In contrast, CatB deficiency did not affect the nerve injury-induced tactile allodynia. Furthermore, CatB deficiency or CA-074Me treatment significantly inhibited the maturation and secretion of IL-1␤ and IL-18 by cultured microglia following treatment with the neuroactive glycoprotein chromogranin A (CGA), but not with ATP. Moreover, the IL-1␤ expression in spinal microglia and the induction of tactile allodynia following the intrathecal administration of CGA depended on CatB, whereas those induced by the intrathecal administration of ATP or lysophosphatidic acid were CatB independent. These results strongly suggest that CatB is an essential enzyme for the induction of chronic inflammatory pain through its activation of pro-caspase-1, which subsequently induces the maturation and secretion of IL-1␤ and IL-18 by spinal microglia. Therefore, CatB-specific inhibitors may represent a useful new strategy for treating inflammation-associated pain.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Microglial Cathepsin B Contributes to the Initiation of Peripheral Inflammation-Induced Chronic Pain

Sun

Hayashi

et al. 2012

J. Neurosci.

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“…Previous study shows that electroacupuncture (EA) significantly increases paw withdrawal latency (PWL) and inhibits intra-plantar CFA-induced up-regulation of glial fibrillary acidic protein, a marker of astrocytes [12]. EA also markedly inhibits intra-articular CFA-induced up-regulation of IL-1β, IL-6, and TNFα in the spinal cord [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Electroacupuncture Inhibits Spinal Interleukin-17A to Alleviate Inflammatory Pain in a Rat Model

Meng¹,

Lao²,

Shen³

et al. 2013

TOPAINJ

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Although acupuncture analgesia has been reported in clinical trials, its mechanisms have been unclear. It was recently reported that spinal astrocytes-produced interleukin-17A (IL-17A) facilitates inflammatory pain. Hypothesizing that electroacupuncture (EA) would suppress inflammation-enhanced IL-17A synthesis to inhibit pain, we induced hyperalgesia, as measured by decreased paw withdrawal latency (PWL) to a noxious thermal stimulus, by subcutaneously injecting complete Freund's adjuvant (CFA, 0.08 ml, 40 µg Mycobacterium tuberculosis) into the hind paws of rats, or intrathecal (i.t.) IL-17A (400 ng in 10 µl) into the lumbar spinal cord. We then gave EA at acupoint GB30 for two 20-min periods, once immediately after CFA or IL-17A administration and again 2 h post-injection. For sham control, EA needles were inserted into GB30 without stimulation. PWL was measured before and 2.5 and 24 h after injection. Spinal IL-17A, IL-17 receptor A (IL-17RA), and phosphorylated NR1, an essential subunit of the N-methyl D-aspartate receptor (NMDAR), were determined 24 h post-CFA or -IL-17A using immunohistochemistry and western blot. Compared to sham control, EA inhibited CFA-caused thermal hyperalgesia 2.5 and 24 h post-CFA and concurrently suppressed inflammation-enhanced IL-17A and IL-17RA synthesis and NR1 phosphorylation in the ipsilateral spinal cord. EA inhibited IL-17A-produced thermal hyperalgesia, IL-17RA synthesis and NR1 phosphorylation. Our data suggest that EA inhibits inflammatory pain by blocking spinal IL-17A synthesis. Since previous study shows that IL-17A is located in astrocytes and IL-17RA and NR1 are in neurons, the data suggest that EA alleviates pain by modulating glia-neuronal interactions that involve IL-17A, IL-17RA, and NR1 phosphorylation.

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“…Recent evidence (Lin et al, 2007;Nakagawa et al, 2007;Shan et al, 2007) suggests that glial cells involved in mediating inflammatory and injury processes are resident within the spinal cord and include both astroglia and microglia, the latter of which has been implicated directly in the initiation of pain. Microglia are known to produce a number of substances and cytokines (McMahon et al, 2005) that can influence the excitability of neurons, including tumor necrosis factor-a (TNF-a), interleukin-b (IL-b; Ferrari et al, 1997), ATP, and brain-derived neurotrophic factor (BDNF; Coull et al, 2005).…”

mentioning

confidence: 99%

Minocycline‐induced reduction of brain‐derived neurotrophic factor expression in relation to cancer‐induced bone pain in rats

Wang

Yang

et al. 2011

J of Neuroscience Research

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Previous studies have suggested that the release of brain-derived neurotrophic factor (BDNF) from microglia in spinal cord is necessary for maintaining pain hypersensitivity after nerve injury. However, little is known about its role in cancer-induced bone pain (CIBP), which is in some ways unique. This study demonstrates a critical role of minocycline (a potent inhibitor of microglial activation)-modulated BDNF in the induction and maintenance of behavioral hypersensitivity in a rat model of CIBP. We assessed mechanical threshold and spontaneous pain of CIBP rats. Moreover, minocycline was administered intrathecally from day 4 to day 6 (early stage) or from day 10 to day 12 (later stage), after carcinoma cell inoculation. Real-time PCR, Western blots, and double immunofluorescence were used to detect the expression of OX-42 (marker of activated microglia), phosphorylated p38-MAPK (p-p38), and BDNF. We found that intrathecal minocycline could prevent CIBP at an early stage of tumor growth (from day 4 to day 6). However, at the late stage (from day 10 to day 12), intrathecal minocycline had no effect. Moreover, the expression of OX-42 and BDNF under CIBP, peaking on day 6, were all reduced after minocycline injection from day 4 to day 6. The ability of minocycline-induced reduction of BDNF in the induction of behavioral hypersensitivity could provide an opportunity for alleviating CIBP.

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Is functional state of spinal microglia involved in the anti-allodynic and anti-hyperalgesic effects of electroacupuncture in rat model of monoarthritis?

Cited by 89 publications

References 49 publications

Microglial Cathepsin B Contributes to the Initiation of Peripheral Inflammation-Induced Chronic Pain

Microglial Cathepsin B Contributes to the Initiation of Peripheral Inflammation-Induced Chronic Pain

Electroacupuncture Inhibits Spinal Interleukin-17A to Alleviate Inflammatory Pain in a Rat Model

Minocycline‐induced reduction of brain‐derived neurotrophic factor expression in relation to cancer‐induced bone pain in rats

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