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Sigma-1 receptors are essential for capsaicin-induced mechanical hypersensitivity: studies with selective sigma-1 ligands and sigma-1 knockout mice
- Source :
- PainReferences. 143(3)
- Publication Year :
- 2008
-
Abstract
- We evaluated the role of sigma(1) receptors on capsaicin-induced mechanical hypersensitivity and on nociceptive pain induced by punctate mechanical stimuli, using wild-type and sigma(1) receptor knockout (sigma(1)-KO) mice and selective sigma(1) receptor-acting drugs. Mutation in sigma(1)-KO mice was confirmed by PCR analysis of genomic DNA and, at the protein level, by [(3)H](+)-pentazocine binding assays. Both wild-type and sigma(1)-KO mice not treated with capsaicin showed similar responses to different intensities of mechanical stimuli (0.05-8 g force), ranging from innocuous to noxious, applied to the hind paw. This indicates that sigma(1) gene inactivation does not modify the perception of punctate mechanical stimuli. The intraplantar (i.pl.) administration of capsaicin induced dose-dependent mechanical allodynia in wild-type mice (markedly reducing both the threshold force necessary to induce paw withdrawal and the latency to paw withdrawal induced by a given force). In contrast, capsaicin was completely unable to induce mechanical hypersensitivity in sigma(1)-KO mice. The high-affinity and selective sigma(1) antagonists BD-1063, BD-1047 and NE-100, administered subcutaneously (s.c.), dose-dependently inhibited mechanical allodynia induced by capsaicin (1 microg,i.pl.), yielding ED(50) (mg/kg) values of 15.80+/-0.93, 29.31+/-1.65 and 40.74+/-7.20, respectively. The effects of the sigma(1) antagonists were reversed by the sigma(1) agonist PRE-084 (32 mg/kg, s.c.). None of the drugs tested modified the responses induced by a painful mechanical punctate stimulus (4 g force) in nonsensitized animals. These results suggest that sigma(1) receptors are essential for capsaicin-induced mechanical hypersensitivity, but are not involved in mechanical nociceptive pain.
- Subjects :
- Agonist
Pain Threshold
Sensory Receptor Cells
medicine.drug_class
Morpholines
Pharmacology
Anisoles
Polymerase Chain Reaction
Piperazines
chemistry.chemical_compound
Mice
Physical Stimulation
medicine
Noxious stimulus
Reaction Time
Animals
Receptors, sigma
Pain Measurement
Mice, Knockout
Sigma-1 receptor
Propylamines
Chemistry
Nociceptors
DNA
Ethylenediamines
Anesthesiology and Pain Medicine
Allodynia
Nociception
Neurology
Spinal Cord
Capsaicin
Hyperalgesia
Anesthesia
Sensory System Agents
Nociceptor
Female
Neurology (clinical)
medicine.symptom
Subjects
Details
- ISSN :
- 18726623
- Volume :
- 143
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- PainReferences
- Accession number :
- edsair.doi.dedup.....dc3f78b8cf1f8e9022356e4eb45af837