Molecular pain, 2017-01, Vol.13, p.1744806917719169
2017
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- Autor(en) / Beteiligte
- Titel
- Activation and expression of μ-calpain in dorsal root contributes to RTX-induced mechanical allodynia
- Ist Teil von
- Molecular pain, 2017-01, Vol.13, p.1744806917719169
- Ort / Verlag
- Los Angeles, CA: SAGE Publications
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Background Calpain is a calcium-dependent cysteine protease, and inhibition of calpain by pre-treatment with MDL28170 attenuated the rat mechanical allodynia in a variety of pain models. Postherpetic neuralgia (Shingles) is a neuropathic pain conditioned with the presence of profound mechanical allodynia. Systemic injection of resiniferatoxin can reproduce the clinical symptoms of postherpetic neuralgia. In this study, we determined to study whether activation of calpain contributes to cleave the myelin basic protein of dorsal root and is involved in resiniferatoxin-induced mechanical allodynia of postherpetic neuralgia animal model. Results Resiniferatoxin up-regulated the expression and activation of µ-calpain in dorsal root. The expression of µ-calpain was located in Schwann cell of dorsal root, and resiniferatoxin increased the expression of µ-calpain in Schwann cell in L4–L6 dorsal root at six weeks after injection. Resiniferatoxin also induced myelin basic protein degradation in L4–L6 dorsal root at six weeks after injection. Moreover, intraperitoneal injection of calpain inhibitor MDL28170 prevented the degradation of myelin basic protein and then reduced the sprouting of myelinated afferent fibers into spinal lamina II, thus relieving resiniferatoxin-induced mechanical allodynia. Conclusions Up-regulation and activation of µ-calpain located in Schwann cell may be the mechanism underlying resiniferatoxin-mediated proteolysis of myelin basic protein in dorsal root. Calpain inhibitor MDL28170 prevents resiniferatoxin-induced sprouting of myelinated afferent fibers and mechanical allodynia through inhibition of degradation of the myelin basic protein in dorsal root. Our results indicate that inhibition of pathological µ-calpain activation may present an interesting novel drug target in the treatment of postherpetic neuralgia.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1744-8069eISSN: 1744-8069DOI: 10.1177/1744806917719169Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5548329
- Format
- –
- Schlagworte
- Animal models, Animals, Biomarkers - metabolism, Calcium, Calpain, Calpain - metabolism, Cysteine proteinase, Degradation, Dipeptides - pharmacology, Diterpenes - administration & dosage, Dorsal roots, Enzyme Activation - drug effects, Fibers, Ganglia, Spinal - enzymology, Ganglia, Spinal - pathology, Herpes zoster, Hyperalgesia - enzymology, Hyperalgesia - pathology, Injection, Lumbar Vertebrae - pathology, Male, Myelin, Myelin basic protein, Myelin Basic Protein - metabolism, Myelin Sheath - metabolism, Neuralgia, Neurons, Afferent - drug effects, Neurons, Afferent - metabolism, Pain perception, Protein Isoforms - metabolism, Proteins, Proteolysis, Proteolysis - drug effects, Rats, Rats, Sprague-Dawley, Resiniferatoxin, Schwann Cells - drug effects, Schwann Cells - enzymology, Sensory neurons, Therapeutic targets, Up-Regulation - drug effects