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Role of Voltage Gated Ca2+ Channels in Rat Visceral Hypersensitivity Change Induced by 2, 4, 6-Trinitrobenzene Sulfonic Acid
- Source :
- Molecular Pain
- Publisher :
- SAGE Publications
-
Abstract
- Background Visceral pain is common symptom involved in many gastrointestinal disorders such as inflammatory bowel disease. The underlying molecular mechanisms remain elusive. We investigated the molecular mechanisms and the role for voltage gated calcium channel (VGCC) in the pathogenesis in a rat model of 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) induced visceral inflammatory hypersensitivity. Results Using Agilent cDNA arrays, we found 172 genes changed significantly in dorsal root ganglia (DRG) of TNBS treated rats. Among these changed genes, Cav1.2 and Cav2.3 were significantly up-regulated. Then the RT-PCR and Western blot further confirmed the up-regulation of Cav1.2 and Cav2.3. The whole cell patch clamp recording of acutely dissociated colonic specific DRG neurons showed that the peak IBa density was significantly increased in colonic neurons of TNBS treated rats compared with control rats (−127.82 ± 20.82 pA/pF Vs −91.67 ± 19.02 pA/pF, n = 9, *P < 0.05). To distinguish the different type of calcium currents with the corresponding selective channel blockers, we found that L-type (−38.56 ± 3.97 pA/pF Vs −25.75 ± 3.35 pA/pF, n = 9, * P < 0.05) and R-type (−13.31 ± 1.36 pA/pF Vs −8.60 ± 1.25 pA/pF, n = 9, * P < 0.05) calcium current density were significantly increased in colonic DRG neurons of TNBS treated rats compared with control rats. In addition, pharmacological blockade with L-type antagonist (nimodipine) and R-type antagonist (SNX-482) with intrathecal injection attenuates visceral pain in TNBS induced inflammatory visceral hypersensitivity. Conclusion Cav1.2 and Cav2.3 in colonic primary sensory neurons play an important role in visceral inflammatory hyperalgesia, which maybe the potential therapeutic targets.
- Subjects :
- Male
Pathology
medicine.medical_specialty
Calcium Channels, L-Type
Colon
Blotting, Western
chemistry.chemical_element
Spider Venoms
Calcium Channels, R-Type
Pharmacology
Calcium
Real-Time Polymerase Chain Reaction
Rats, Sprague-Dawley
Cellular and Molecular Neuroscience
Visceral sensory
Ganglia, Spinal
medicine
Hypersensitivity
Animals
Channel blocker
Patch clamp
Dorsal root ganglia
Nimodipine
Cation Transport Proteins
Injections, Spinal
Voltage gated calcium channels
Voltage-dependent calcium channel
Chemistry
Gene Expression Profiling
Research
Antagonist
Visceral pain
Carbocyanines
TNBS
Rats
Protein Subunits
Viscera
Anesthesiology and Pain Medicine
Trinitrobenzenesulfonic Acid
Hyperalgesia
Molecular Medicine
[Ca2+]i
medicine.symptom
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 17448069
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Molecular Pain
- Accession number :
- edsair.doi.dedup.....78f043c7c5e722ef8f6f04f4b41f9991
- Full Text :
- https://doi.org/10.1186/1744-8069-9-15