01 June 2012
Osthole, a herbal compound, alleviates nucleus pulposus-evoked nociceptive responses through the suppression of overexpression of acid-sensing ion channel 3 (ASIC3) in rat dorsal root ganglion
Qiu-Lan HeABCDEF, Yuling ChenABCDEF, Jian QinABCD, Sui-Lin MoABCDE, Ming WeiABCD, Jin-Jun ZhangABCD, Mei-Na LiABCD, Xue-Nong ZouDE, Shu-Feng ZhouABCDEF, Xiao-Wu ChenABCD, Lai-Bao SunABCDEFGDOI: 10.12659/MSM.882899
Med Sci Monit 2012; 18(6): BR229-236
Abstract
Background: Osthole (Ost), a natural coumarin derivative, has been shown to inhibit many pro-inflammatory mediators and block voltage-gated Na+ channels. During inflammation, acidosis is an important pain inducer which activates nociceptors by gating depolarizing cationic channels, such as acid-sensing ion channel 3 (ASIC3). The aim of this study was to examine the effects of Ost on nucleus pulposus-evoked nociceptive responses and ASIC3 over-expression in the rat dorsal root ganglion, and to investigate the possible mechanism.
Material/Methods: Radicular pain was generated with application of nucleus pulposus (NP) to nerve root. Mechanical allodynia was evaluated using von Frey filaments with logarithmically incremental rigidity to calculate the 50% probability thresholds for mechanical paw withdrawal. ASIC3 protein expression in dorsal root ganglions (DRGs) was assessed with Western blot and immunohistochemistry. Membrane potential (MP) shift of DRG neurons induced by ASIC3-sensitive acid (pH6.5) was determined by DiBAC4 (3) fluorescence intensity (F.I.).
Results: The NP-evoked mechanical hyperalgesia model showed allodynia for 3 weeks, and ASIC3 expression was up-regulated in DRG neurons, reaching peak on Day 7. Epidural administration of Ost induced a remarkable and prolonged antinociceptive effect, accompanied by an inhibition of over-expressed ASIC3 protein and of abnormal shift of MP. Amiloride (Ami), an antagonist of ASIC3, strengthened the antinociceptive effect of Ost.
Conclusions: Up-regulation of ASIC3 expression may be associated with NP-evoked mechanical hyperalgesia. A single epidural injection of Ost decreased ASIC3 expression in DGR neurons and the pain in the NP-evoked mechanical hyperalgesia model. Osthole may be of great benefit for preventing chronic pain status often seen in lumbar disc herniation (LDH).
Keywords: Nociception - drug effects, Pain - physiopathology, Neurons - pathology, Nerve Tissue Proteins - metabolism, Membrane Potentials - drug effects, Intervertebral Disc - pathology, Hyperalgesia - physiopathology, Hydrogen-Ion Concentration - drug effects, Ganglia, Spinal - pathology, Fluorescent Antibody Technique, Coumarins - therapeutic use, Blotting, Western, Analgesics - pharmacology, Acid Sensing Ion Channels, Pain Threshold - drug effects, Phytotherapy, Plant Preparations - therapeutic use, Sodium Channels - metabolism
Editorial
01 January 2023 : Editorial
Editorial: Current Status of Two Adjuvanted Malaria Vaccines and the World Health Organization (WHO) Strategy to Eradicate Malaria by 2030DOI: 10.12659/MSM.939357
Med Sci Monit 2023; 29:e939357
SARS-CoV-2/COVID-19
26 January 2023 : Editorial
Editorial: The XBB.1.5 (‘Kraken’) Subvariant of Omicron SARS-CoV-2 and its Rapid Global SpreadMed Sci Monit In Press; DOI: 10.12659/MSM.939580
19 January 2023 : Clinical Research
Evaluation of Health-Related Quality of Life and Mental Health in 729 Medical Students in Indonesia During ...Med Sci Monit In Press; DOI: 10.12659/MSM.938892
19 January 2023 : Clinical Research
Determining the Impact of the COVID-19 Pandemic on Dental Care in the Serbian Adult Population: An Online Q...Med Sci Monit 2023; 29:e939238
27 December 2022 : Clinical Research
Effect of Physiotherapy to Correct Rounded Shoulder Posture in 30 Patients During the COVID-19 Pandemic in ...Med Sci Monit 2022; 28:e938926
In Press
27 Jan 2023 : Database Analysis
Association Between Neutrophil-Lymphocyte Ratio and All-Cause Mortality in Critically Ill Patients with Chr...Med Sci Monit In Press; DOI: 10.12659/MSM.938554
27 Jan 2023 : Clinical Research
Proposal for a Simple Equation for Limb Muscle Weight CalculationMed Sci Monit In Press; DOI: 10.12659/MSM.938606
26 Jan 2023 : Editorial
Editorial: The XBB.1.5 (‘Kraken’) Subvariant of Omicron SARS-CoV-2 and its Rapid Global SpreadMed Sci Monit In Press; DOI: 10.12659/MSM.939580
20 Jan 2023 : Clinical Research
A Study of 42 Partially Edentulous Patients with Single-Crown Restorations and Implants to Compare Bone Los...Med Sci Monit In Press; DOI: 10.12659/MSM.939225
Most Viewed Current Articles
13 Nov 2021 : Clinical Research
Acceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...DOI :10.12659/MSM.932788
Med Sci Monit 2021; 27:e932788
30 Dec 2021 : Clinical Research
Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...DOI :10.12659/MSM.935379
Med Sci Monit 2021; 27:e935379
08 Mar 2022 : Review article
A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...DOI :10.12659/MSM.936292
Med Sci Monit 2022; 28:e936292
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952