Spinal Heme Oxygenase-1 (HO-1) Exerts Antinociceptive Effects Against Neuropathic Pain in a Mouse Model of L5 Spinal Nerve Ligation

Liu, Xiaoming; Zhang, Zhijun; Zhang, Cheng; Zhang, Jie; Xu, Shuping; Liu, Hongjun; Jia, Hong-Ti; Jin, Yi

doi:10.1111/pme.12906

Cited by 22 publications

(32 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A few recent studies have begun to investigate the physiology of viable human DRG neurons and have highlighted some similarities as well as some potentially important differences in how human DRG neurons respond to stimuli previously tested only in rodents [14; 29; 31; 52]. However, our study is the first to show that inflammation-induced sensitization of human nociceptors, a neural correlate of hyperalgesia, can be blocked by a candidate analgesic in vitro .…”

Section: Discussionmentioning

confidence: 72%

Group II mGluRs suppress hyperexcitability in mouse and human nociceptors

Davidson

Golden

Copits

et al. 2016

Pain

View full text Add to dashboard Cite

We introduce a strategy for preclinical research wherein promising targets for analgesia are tested in rodent and subsequently validated in human sensory neurons. Here, we evaluate group II metabotropic glutamate receptors, the activation of which is efficacious in rodent models of pain. Immunohistochemical analysis showed positive immunoreactivity for mGlu2 in rodent dorsal root ganglia (DRG), peripheral fibers in skin, and central labeling in spinal dorsal horn. We also found mGlu2-positive immunoreactivity in human neonatal and adult DRG. RNA-seq analysis of mouse and human DRG revealed a comparative expression profile between species for group II mGluRs and for opioid receptors. In rodent sensory neurons under basal conditions, activation of group II mGluRs with a selective group II agonist produced no changes to membrane excitability. However, membrane hyperexcitability in sensory neurons exposed to the inflammatory mediator prostaglandin E2 (PGE2) was prevented by (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC). In human sensory neurons from donors without history of chronic pain, we show that PGE2 produced hyperexcitability that was similarly blocked by group II mGluR activation. These results reveal a mechanism for peripheral analgesia likely shared by mouse and human and demonstrate a translational research strategy to improve preclinical validation of novel analgesics using cultured human sensory neurons.

show abstract

Section: Discussionmentioning

confidence: 72%

Group II mGluRs suppress hyperexcitability in mouse and human nociceptors

Davidson

Golden

Copits

et al. 2016

Pain

View full text Add to dashboard Cite

show abstract

“…Finally, an important role of HO-1 in reducing neuropathic pain has been recently pointed out, showing that HO-1 up-regulation could elicit potent analgesic effects in part due to the inhibition of spinal microglia activation, as shown in a mouse model of peripheral nerve injury [102] or favoring the antinociceptive effect of morphine in diabetic animals [103]. It has been also shown that the HO-1 dependent reduction of neuropathic pain is due to the specific modulation of MAPKs and Nrf2 and the reduction of oxidative stress and neuroinflammation in prefrontal cortex and hypothalamus [104].…”

Section: Ho-1 Protective Effects In Nervous Systemmentioning

confidence: 99%

Heme Oxygenase 1 in the Nervous System: Does It Favor Neuronal Cell Survival or Induce Neurodegeneration?

Nitti

Piras

Brondolo

et al. 2018

IJMS

123

107

View full text Add to dashboard Cite

Heme oxygenase 1 (HO-1) up-regulation is recognized as a pivotal mechanism of cell adaptation to stress. Under control of different transcription factors but with a prominent role played by Nrf2, HO-1 induction is crucial also in nervous system response to damage. However, several lines of evidence have highlighted that HO-1 expression is associated to neuronal damage and neurodegeneration especially in Alzheimer’s and Parkinson’s diseases. In this review, we summarize the current literature regarding the role of HO-1 in nervous system pointing out different molecular mechanisms possibly responsible for HO-1 up-regulation in nervous system homeostasis and neurodegeneration.

show abstract

“…The number of 6 animals per group was determined from a pilot study taking into account a value of α = 0.01 and β = 0.10. The doses and time points of CORM-2 chosen were selected from preliminary experiments shown to be effective in producing neuropathic pain relief [ 9 , 31 ] as well as from our previous pilot studies performed in the Stz-induced diabetic neuropathy mouse model.…”

Section: Methodsmentioning

confidence: 99%

Administration of CORM-2 inhibits diabetic neuropathy but does not reduce dyslipidemia in diabetic mice

et al. 2018

View full text Add to dashboard Cite

The antinociceptive effects of the carbon monoxide-releasing molecule tricarbonyldichlororuthenium (II) dimer (CORM-2) during chronic pain are well documented, but most of its possible side-effects remain poorly understood. In this work, we examine the impact of CORM-2 treatment on the lipoprotein profile and two main atheroprotective functions attributed to high-density lipoprotein (HDL) in a mouse model of type 1 diabetes while analyzing the effect of this drug on diabetic neuropathy. Streptozotocin (Stz)-induced diabetic mice treated with CORM-2 (Stz-CORM-2) or vehicle (Stz-vehicle) were used to evaluate the effect of this drug on the modulation of painful diabetic neuropathy using nociceptive behavioral tests. Plasma and tissue samples were used for chemical and functional analyses, as appropriate. Two main antiatherogenic properties of HDL, i.e., the ability of HDL to protect low-density lipoprotein (LDL) from oxidation and to promote reverse cholesterol transport from macrophages to the liver and feces in vivo (m-RCT), were also assessed. Stz-induced diabetic mice displayed hyperglycemia, dyslipidemia and pain hypersensitivity. The administration of 10 mg/kg CORM-2 during five consecutive days inhibited allodynia and hyperalgesia and significantly ameliorated spinal cord markers (Cybb and Bdkrb1expression) of neuropathic pain in Stz mice, but it did not reduce the combined dyslipidemia shown in Stz-treated mice. Its administration to Stz-treated mice led to a significant increase in the plasma levels of cholesterol (∼ 1.4-fold vs. Ctrl, ∼ 1.3- fold vs. Stz-vehicle; p < 0.05) and was attributed to significant elevations in both non-HDL (∼ 1.8-fold vs. Ctrl; ∼ 1.6-fold vs. Stz-vehicle; p < 0.05) and HDL cholesterol (∼ 1.3-fold vs. Ctrl, ∼ 1.2-fold vs. Stz-vehicle; p < 0.05). The increased HDL in plasma was not accompanied by a commensurate elevation in m-RCT in Stz-CORM-2 compared to Stz-vehicle mice; instead, it was worsened as revealed by decreased [3H]-tracer trafficking into the feces in vivo. Furthermore, the HDL-mediated protection against LDL oxidation ex vivo shown by the HDL isolated from Stz-CORM-2 mice did not differ from that obtained in Stz-vehicle mice. In conclusion, the antinociceptive effects produced by a high dose of CORM-2 were accompanied by antioxidative effects but were without favorable effects on the dyslipidemia manifested in diabetic mice.

show abstract

Spinal Heme Oxygenase-1 (HO-1) Exerts Antinociceptive Effects Against Neuropathic Pain in a Mouse Model of L5 Spinal Nerve Ligation

Abstract: HO-1 upregulation could elicit potent analgesic effects against neuropathic pain, which might partly be attributed to inhibition of spinal microglia activation. HO-1 signaling pathway may present a novel strategy for the treatment of neuropathic pain.

Cited by 22 publications

References 40 publications

Group II mGluRs suppress hyperexcitability in mouse and human nociceptors

Group II mGluRs suppress hyperexcitability in mouse and human nociceptors

Heme Oxygenase 1 in the Nervous System: Does It Favor Neuronal Cell Survival or Induce Neurodegeneration?

Administration of CORM-2 inhibits diabetic neuropathy but does not reduce dyslipidemia in diabetic mice

Contact Info

Product

Resources

About