The Role of Spinal GABAB Receptors in Cancer-Induced Bone Pain in Rats

Zhou, Ya‐Qun; Chen, Shuping; Liu, Dai-Qiang; Manyande, Anne; Zhang, Wen; Yang, Shaobing; Xiong, Bingrui; Fu, Qiaochu; Song, Zhenpeng; Rittner, Heike L.; Ye, Dawei; Tian, Yuan

doi:10.1016/j.jpain.2017.02.438

Cited by 35 publications

(23 citation statements)

References 58 publications

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“…Taken together, these results provided strong evidence that the CaMKII/CREB signaling pathway may be a critical downstream pathway of CXCR4 under BCP situation, indicating that suppressing the activation of CaMKII/CREB signaling pathway may be an alternative therapeutic strategy for the management of BCP. In addition, our recent study also confirmed the role of CREB under BCP condition (Zhou et al, 2017).…”

Section: Camkii and Bone Cancer Painsupporting

confidence: 73%

Cellular and Molecular Mechanisms of Calcium/Calmodulin-Dependent Protein Kinase II in Chronic Pain

Zhou

Liu

Chen

et al. 2017

J Pharmacol Exp Ther

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Chronic pain, often defined as any pain lasting more than 3 months, is poorly managed because of its multifaceted and complex mechanisms. Calcium/calmodulin-dependent protein kinase II (CaMKII) is a multifunctional serine/threonine kinase that plays a fundamental role in synaptic plasticity, learning, and memory. Recent emerging evidence demonstrates increased expression and activity of CaMKII in the spinal cord and dorsal root ganglia of various chronic pain models. Moreover, our previous studies also find that inhibiting CaMKII could attenuate inflammatory pain and neuropathic pain. In this review, we provide evidence for the involvement of CaMKII in the initiation and development of chronic pain, including neuropathic pain, bone cancer pain, and inflammatory pain. Novel CaMKII inhibitors with potent inhibitory effect and high specificity may be alternative therapeutic strategies for the management of chronic pain in the future.

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Section: Camkii and Bone Cancer Painsupporting

confidence: 73%

Cellular and Molecular Mechanisms of Calcium/Calmodulin-Dependent Protein Kinase II in Chronic Pain

Zhou

Liu

Chen

et al. 2017

J Pharmacol Exp Ther

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“…Suspensions of tumor cells (4 × 10 7 cells/mL) in phosphate buffer saline (PBS) were prepared for injection using a hemocytometer. The model of CIBP was performed as described previously [15] , [16] . In brief, the right leg was disinfected after anesthetized with pentobarbital sodium (50 mg/kg, intraperitoneal, i.p.).…”

Section: Methodsmentioning

confidence: 99%

“…The sections were then captured using a fluorescence microscope (DM2500, Leica, Germany). The Iba1-immunolabeled surface areas were measured in laminae I-IV of the spinal cord dorsal horn using Image Pro Plus software as described previously [15] . Quantification of the immunoreactivity was accomplished by calculating the percentages of immunostaining ([positive immunofluorescent surface area]/[total measured picture area] × 100).…”

Section: Methodsmentioning

confidence: 99%

Reactive oxygen species scavengers ameliorate mechanical allodynia in a rat model of cancer-induced bone pain

et al. 2018

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Cancer-induced bone pain (CIBP) is a frequent complication in patients suffering from bone metastases. Previous studies have demonstrated a pivotal role of reactive oxygen species (ROS) in inflammatory and neuropathic pain, and ROS scavengers exhibited potent antinociceptive effect. However, the role of spinal ROS remains unclear. In this study, we investigated the analgesic effect of two ROS scavengers in a well-established CIBP model. Our results found that intraperitoneal injection of N-tert-Butyl-α-phenylnitrone (PBN, 50 and 100 mg/kg) and 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol, 100 and 200 mg/kg) significantly suppressed the established mechanical allodynia in CIBP rats. Moreover, repeated injection of PBN and Tempol showed cumulative analgesic effect without tolerance. However, early treatment with PBN and Tempol failed to prevent the development of CIBP. Naive rats received repetitive injection of PBN and Tempol showed no significant change regarding the nociceptive responses. Finally, PBN and Tempol treatment notably suppressed the activation of spinal microglia in CIBP rats. In conclusion, ROS scavengers attenuated established CIBP by suppressing the activation of microglia in the spinal cord.

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“…For drug administration, intrathecal (i.t.) catheters were implanted using a lumbar approach, as described previously ( Zhou et al, 2017 ). Briefly, animals were anesthetized with intraperitoneal injection (i.p.)…”

Section: Methodsmentioning

confidence: 99%

Endoplasmic Reticulum Stress in Spinal Cord Contributes to the Development of Morphine Tolerance

Liu

Zhou

Peng

et al. 2018

Front. Mol. Neurosci.

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Morphine tolerance remains an intractable problem, which hinders its prolonged use in clinical practice. Endoplasmic reticulum (ER) stress has been proved to play a fundamental role in the pathogenesis of Alzheimer’s disease, diabetes, atherosclerosis, cancer, etc. In this study, we provide the first direct evidence that ER stress may be a significant driver of morphine tolerance. Binding immunoglobulin protein (BiP), the ER stress marker, was significantly upregulated in neurons in spinal dorsal horn in rats being treated with morphine for 7 days. Additionally, chronic morphine treatment resulted in the activation of three arms of unfolded protein response (UPR): inositol-requiring enzyme 1/X-box binding protein 1 (IRE1/XBP1), protein kinase RNA-like ER kinase/eukaryotic initiation factor 2 subunit alpha (PERK/eIF2α), and activating transcription factor 6 (ATF6). More importantly, inhibiting either one of the three cascades could attenuate the development of morphine tolerance. Taken together, our results suggest that ER stress in spinal cord might contribute to the development of morphine tolerance. These findings implicate a potential clinical strategy for preventing morphine tolerance and may contribute to expanding the morphine usage in clinic.

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The Role of Spinal GABAB Receptors in Cancer-Induced Bone Pain in Rats

Cited by 35 publications

References 58 publications

Cellular and Molecular Mechanisms of Calcium/Calmodulin-Dependent Protein Kinase II in Chronic Pain

Cellular and Molecular Mechanisms of Calcium/Calmodulin-Dependent Protein Kinase II in Chronic Pain

Reactive oxygen species scavengers ameliorate mechanical allodynia in a rat model of cancer-induced bone pain

Endoplasmic Reticulum Stress in Spinal Cord Contributes to the Development of Morphine Tolerance

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