Article

Characterization of NF-kB-mediated inhibition of catechol-O-methyltransferase.

Center for Neurosensory Disorders, School of Dentistry, University of North Carolina, Chapel Hill, NC 27599-7455, USA.
Molecular Pain (Impact Factor: 3.53). 02/2009; 5:13. DOI: 10.1186/1744-8069-5-13
Source: PubMed

ABSTRACT Catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines, has recently been implicated in the modulation of pain. Specifically, low COMT activity is associated with heightened pain perception and development of musculoskeletal pain in humans as well as increased experimental pain sensitivity in rodents.
We report that the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) downregulates COMT mRNA and protein in astrocytes. Examination of the distal COMT promoter (P2-COMT) reveals a putative binding site for nuclear factor kappaB (NF-kappaB), the pivotal regulator of inflammation and the target of TNFalpha. Cell culture assays and functional deletion analyses of the cloned P2-COMT promoter demonstrate that TNFalpha inhibits P2-COMT activity in astrocytes by inducing NF-kappaB complex recruitment to the specific kappaB binding site.
Collectively, our findings provide the first evidence for NF-kappaB-mediated inhibition of COMT expression in the central nervous system, suggesting that COMT contributes to the pathogenesis of inflammatory pain states.

0 Bookmarks
 · 
127 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Neuropathic pain responds poorly to drug treatments, and partial relief is achieved in only about half of the patients. Puerarin, the main constituent of Puerariae Lobatae Radix, has been used extensively in China to treat hypertension and tumor. The current study examined the effects of puerarin on neuropathic pain using two most commonly used animal models: chronic constriction injury (CCI) and diabetic neuropathy. We found that consecutive intrathecal administration of puerarin (4-100 nM) for 7 days inhibited the mechanical and thermal nociceptive response induced by CCI and diabetes without interfering with the normal pain response. Meanwhile, in both models puerarin inhibited the activation of microglia and astroglia in the spinal dorsal horn. Puerarin also reduced the upregulated levels of nuclear factor-κB (NF-κB) and other proinflammatory cytokines, such as IL-6, IL-1β, and TNF-α, in the spinal cord. In summary, puerarin alleviated CCI- and diabetes-induced neuropathic pain, and its effectiveness might be due to the inhibition of neuroinflammation in the spinal cord. The anti-inflammation effect of puerarin might be related to the suppression of spinal NF-κB activation and/or cytokines upregulation. We conclude that puerarin has a significant effect on alleviating neuropathic pain and thus may serve as a therapeutic approach for neuropathic pain.
    Mediators of Inflammation 01/2014; 2014:485927. · 2.42 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To assess the effect of bone marrow mononuclear cells (BMMNCs) transplantation in the expression of nuclear factor-κB (NF-κB) in spinal cord injury (SCI) in rats. BMMNCs were isolated from tibia and femur by a density gradient centrifugation. After establishment of acute transection SCI, rats were divided into experiment (BMMNCs), experiment control (0.1 M PBS infused) and sham surgery groups (laminectomy without any SCI). Locomotor function was assessed weekly for 5 weeks post-injury using BBB locomotor score and urinary bladder function daily for 4 weeks post-injury. Activity of NF-κB in spinal cord was assessed by immunohistochemistry and reverse transcriptase polymerase chain reaction. At each time point post-injury, sham surgery group had significantly higher Basso, Beattie, Bresnahan locomotor and urinary bladder function scores than experiment and experiment control group (p<0.05). At subsequent time interval there were gradual improvement in both experiment and experiment control group, but experiment group had higher score in comparison to experiment control group (p<0.05). Comparisons were also made for expression of activated NF-κB positive cells and level of NF-κB messenger RNA in spinal cord at various time points between the groups. Activated NF-κB immunoreactivity and level of NF-κB mRNA expression were significantly higher in control group in comparison to experiment and sham surgery group (p<0.05). BMMNCs transplantation attenuates the expression of NF-κB in injured spinal cord tissue and thus helps in recovery of neurological function in rat models with SCI.
    Journal of Korean Neurosurgical Society 11/2014; 56(5):375-82. · 0.52 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Neuropathic pain is a major health issue that represents considerable social and economic burden worldwidely. In this study, we investigated the potential of catalpol, an iridoid glucoside of Rehmannia glutinosa Steud, to alleviate neuropathic pain. The potential analgesic effects of catalpol were evaluated by chronic constriction injury (CCI) and lumbar 5 spinal nerve ligation (L5 SNL) model. In addition, we explored whether catalpol altered the degree of microglia activation and neuroinflammation in rat spinal cord after CCI induction. Repeated administration of catalpol (1, 5, 25, and 125 mg/kg) reversed mechanical allodynia induced by CCI and L5 SNL in a dose-dependent manner in rats. Levels of activated microglia, activated NF-κB, and proinflammatory cytokines (IL-1β, IL-6, TNF-α) in lumber spinal cord were elevated in rats following CCI induction, and catalpol significantly inhibited these effects. Our results demonstrated that catalpol produces significant antinociceptive action in rodent behavioral models of neuropathic pain and that this effect is associated with modulation of neuroinflammation in spinal cord.
    Cell Biochemistry and Biophysics 07/2014; · 2.38 Impact Factor

Full-text (3 Sources)

Download
33 Downloads
Available from
Jun 2, 2014