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Analgesic effects of prostaglandin E2 receptor subtype EP1 receptor antagonist: experimental study of application of nucleus pulposus
- Source :
- Spine. 36(22)
- Publication Year :
- 2011
-
Abstract
- STUDY DESIGN The effect of an EP1 receptor antagonist on pain-related behavior induced by nucleus pulposus (NP) applied to the dorsal root ganglion (DRG) in rats was investigated. OBJECTIVE We investigated pain-related behavior, the amount of prostaglandin E2 (PGE2), and neural damage to the DRG after application of NP to the DRG after administration of an EP1 receptor antagonist. SUMMARY OF BACKGROUND DATA PGE2 induces mechanical allodynia and hyperalgesia, which are mediated by PGE2 receptors. EP1 is one of the PGE2 receptor subtypes. An EP1 antagonist reduces hyperalgesia, allodynia, and c-fos expression in the rat chronic nerve constriction model. METHODS Sprague-Dawley rats (n = 103) were used. Animals receiving NP were divided into three experimental groups (n = 12 in each group): saline, high-dose (5 mg/kg) EP1 receptor antagonist (RA), and low-dose (2.5 mg/kg) EP1-RA (orally once daily for 5 days). Animals in the sham group did not receive NP. Von Frey tests were used for pain-behavior testing. The amount of PGE2 in DRG and the number of activating transcription factor-3 (ATF3) immunoreactive positive cells were compared among groups. RESULTS The mechanical thresholds in the three groups decreased 7 days after surgery (just before treatment). The threshold in both the high- and low-dose EP1-RA groups increased at 11 days (5 days after treatment) and continued for 14 days. The thresholds in both the low- and high-dose EP1-RA groups increased significantly compared with the saline group (P < 0.05). The amount of PGE2 was significantly increased in the NP group compared with the sham and naive animals after application of NP. ATF3 expression was increased by NP but was not increased after administration of the EP1-RA. CONCLUSION An EP1 receptor antagonist improves pain-related behavior in the rat model and might be a potential agent to improve pain-related behavior in patients with lumbar disc herniation.
- Subjects :
- Pain Threshold
Time Factors
medicine.drug_class
Prostaglandin E2 receptor
Prostaglandin
Pharmacology
Dinoprostone
Rats, Sprague-Dawley
chemistry.chemical_compound
Ganglia, Spinal
medicine
Animals
Orthopedics and Sports Medicine
Prostaglandin E2
Receptor
Intervertebral Disc
Pain Measurement
Analgesics
Activating Transcription Factor 3
Lumbar Vertebrae
Behavior, Animal
business.industry
Antagonist
Receptor antagonist
Receptors, Prostaglandin E, EP1 Subtype
Rats
Disease Models, Animal
Allodynia
chemistry
Cinnamates
Hyperalgesia
lipids (amino acids, peptides, and proteins)
Female
Neurology (clinical)
medicine.symptom
business
Intervertebral Disc Displacement
medicine.drug
Subjects
Details
- ISSN :
- 15281159
- Volume :
- 36
- Issue :
- 22
- Database :
- OpenAIRE
- Journal :
- Spine
- Accession number :
- edsair.doi.dedup.....879536ccaf6ed56339c0d2db7a8f2a71