Biphasic effects of chronic intrathecal gabapentin administration on the expression of protein kinase C gamma in the spinal cord of neuropathic pain rats

Yeh, Chin Yi; Chung, Shih Chieh; Tseng, Fan Ling; Tsai, Yu Chuan; Liu, Yen Chin

doi:10.1016/j.aat.2011.11.006

Cited by 14 publications

(13 citation statements)

References 24 publications

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“…GBP can potently block TSP-induced formation of excitatory synapses (Dolphin, 2013; Eroglu et al, 2009; Hendrich et al, 2008). Additionally, GBP can modulate PKC signaling in the spinal cord dorsal horn (Yeh et al, 2011; Zhang et al, 2015) and regulate NMDA receptor function via PKC (Gu and Huang, 2001). Furthermore, activation of PKC can accelerate SERCA Ca 2+ uptake into ER (Usachev et al, 2006).…”

Section: Resultsmentioning

confidence: 99%

“…By binding with α 2 δ 1 calcium subunit, TSP4 modulates SERCA and PMCA through a PKC dependent pathway that links activation of α 2 δ 1 Ca 2+ subunit and inhibition of SERCA function. Additional evidence of this role of PKC comes from a report that shows GBP regulation of PKC signaling in the spinal cord of rats underlying neuropathic pain (Yeh et al, 2011). …”

Section: Discussionmentioning

confidence: 99%

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Increased thrombospondin-4 after nerve injury mediates disruption of intracellular calcium signaling in primary sensory neurons

Guo

Zhang

et al. 2017

Neuropharmacology

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Painful nerve injury disrupts Ca2+ signaling in primary sensory neurons by elevating plasma membrane Ca2+-ATPase (PMCA) function and depressing sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) function, which decreases endoplasmic reticulum (ER) Ca2+ stores and stimulates store-operated Ca2+ entry (SOCE). The extracellular matrix glycoprotein thrombospondin-4 (TSP4), which is increased after painful nerve injury, decreases Ca2+ current (ICa) through high-voltage–activated Ca2+ channels and increases ICa through low-voltage–activated Ca2+ channels in dorsal root ganglion neurons, which are events similar to the effect of nerve injury. We therefore examined whether TSP4 plays a critical role in injury-induced disruption of intracellular Ca2+ signaling. We found that TSP4 increases PMCA activity, inhibits SERCA, depletes ER Ca2+ stores, and enhances store-operated Ca2+ influx. Injury-induced changes of SERCA and PMCA function are attenuated in TSP4 knock-out mice. Effects of TSP4 on intracellular Ca2+ signaling are attenuated in voltage-gated Ca2+ channel α2δ1 subunit (Cavα2δ1) conditional knock-out mice and are also Protein Kinase C (PKC) signaling dependent. These findings suggest that TSP4 elevation may contribute to the pathogenesis of chronic pain following nerve injury by disrupting intracellular Ca2+ signaling via interacting with the Cavα2δ1 and the subsequent PKC signaling pathway. Controlling TSP4 mediated intracellular Ca2+ signaling in peripheral sensory neurons may be a target for analgesic drug development for neuropathic pain.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Increased thrombospondin-4 after nerve injury mediates disruption of intracellular calcium signaling in primary sensory neurons

Guo

Zhang

et al. 2017

Neuropharmacology

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“…Gabapentin is also used as an anti-convulsant drug and is now widely becoming accepted as an alternative treatment for various types of neuropathic and inflammatory pain (Boroujerdi et al 2011; Thomas and Farquhar-Smith 2011; Yeh et al 2011). Gabapentin also has a well-established role in the attenuation of morphine tolerance.…”

Section: Introductionmentioning

confidence: 99%

Gabapentin Enhances the Morphine Anti-Nociceptive Effect in Neuropathic Pain via the Interleukin-10-Heme Oxygenase-1 Signalling Pathway in Rats

et al. 2014

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In the present study, we investigated the anti-inflammatory mechanisms by which gabapentin enhances morphine anti-nociceptive effect in neuropathic pain in rats and the interaction between the anti-nociceptive effects of gabapentin on morphine and the interleukin (IL)-10-heme-oxygenase (HO)-1 signal pathway in a rat model of neuropathic pain. The neuropathic pain model was induced via a left L5/6 spinal nerve ligation (SNL) in rats. The anti-nociceptive effect of gabapentin and IL-10 on morphine was examined over a 7-day period, and the effects of the anti-IL-10 and HO-1 inhibitor zinc protoporphyrin (ZnPP) on gabapentin/morphine co-injection were assessed. Drug administration was given over 7 days, and on day 8, both anti-inflammatory cytokine IL-10, a stress-induced protein HO-1 and pro-inflammatory cytokines IL-1β, IL-6 and TNF-α were measured. Gabapentin attenuated morphine tolerance over 7 days of co-administration, and reduced the expression of pro-inflammatory cytokines but increased IL-10 and HO-1 expression. The effect of gabapentin on morphine was partially blocked using the anti-IL-10 antibody or the HO-1 inhibitor zinc protoporphyrin. Our findings indicated that the anti-nociceptive effects of gabapentin on morphine might be caused by activation of the IL-10-HO-1 signalling pathway, which resulted in the inhibition of the expression of pro-inflammatory cytokines in neuropathic pain in the rat spinal cord.

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“…(ii) Other ion channels and receptors: GBP has been shown to inhibit transient receptor potential A1 channels and N‐methyl‐D‐aspartate receptors . (iii) Metabolic effects: these include enhancement of GABA synthesis from L‐glutamate , inhibition of protein kinase C and decreased expression and phosphorylation of CaMKII .…”

Section: Discussionmentioning

confidence: 99%

Gabapentin, an Analgesic Used Against Cancer‐Associated Neuropathic Pain: Effects on Prostate Cancer Progression in an In Vivo Rat Model

Bugan

Karagoz

Altun

et al. 2015

Basic Clin Pharma Tox

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A major problem associated with clinical management of cancer is controlling the accompanying pain, and various analgesics are in common use for this purpose. Recent evidence suggests that some of the targets of analgesics, such as ion channels and receptors, may also be involved in the cancer process, thereby raising the possibility that such use of some analgesics may impact upon cancer itself. The main aim of this study was to determine whether gabapentin, a common adjuvant analgesic in current use against cancer-associated neuropathic pain, would affect tumour development and progression in vivo. The Dunning rat model of prostate cancer was used. Strongly metastatic Mat-LyLu cells were implanted subcutaneously into syngeneic Copenhagen rats which were then treated every other day with 4.6-16.8 lg/kg gabapentin by gavage. Primary tumourigenesis was monitored daily. Lung metastases were counted and measured after killing the rats 21 days later. Gabapentin had no effect on primary tumourigenesis but produced dose-dependent effects on lung metastasis. Whilst 4.6 lg/kg had no effect, 9.1 lg/kg gabapentin decreased the number of lung metastases significantly by 64%. In contrast, 16.8 lg/kg gabapentin promoted metastasis significantly by 112% and showed a strong tendency to shorten mean survival time. It is concluded that gabapentin prescribed to cancer patients against pain could impact upon the cancer process itself.

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Biphasic effects of chronic intrathecal gabapentin administration on the expression of protein kinase C gamma in the spinal cord of neuropathic pain rats

Cited by 14 publications

References 24 publications

Increased thrombospondin-4 after nerve injury mediates disruption of intracellular calcium signaling in primary sensory neurons

Increased thrombospondin-4 after nerve injury mediates disruption of intracellular calcium signaling in primary sensory neurons

Gabapentin Enhances the Morphine Anti-Nociceptive Effect in Neuropathic Pain via the Interleukin-10-Heme Oxygenase-1 Signalling Pathway in Rats

Gabapentin, an Analgesic Used Against Cancer‐Associated Neuropathic Pain: Effects on Prostate Cancer Progression in an In Vivo Rat Model

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