Spinal Cord Transection-Induced Allodynia in Rats - Behavioral, Physiopathological and Pharmacological Characterization

Autor: Caroline Chevarin, Sandrine Barthélémy, Michel Hamon, Sylvie Bourgoin, Saïd M'Dahoma, Didier Orsal, Valérie Kayser, Farah Chali
Přispěvatelé: Neuropsychopharmacologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurobiologie des signaux intercellulaires (NSI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Psychiatrie et Neurosciences (U894), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), HAL UPMC, Gestionnaire, Unité de Neuropsychopharmacologie [CHU Pitié-Salpétriêre], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Psychiatrie et Neurosciences ( CPN - U894 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Laboratoire de neurobiologie des signaux intercellulaires, CNRS UMR 7101, Université Pierre et Marie Curie - Paris 6 ( UPMC )
Rok vydání: 2013
Předmět:
Male
Hot Temperature
Physiology
Pregabalin
lcsh:Medicine
Nervous System
Rats
Sprague-Dawley
Ganglia
Spinal
Medicine and Health Sciences
Medicine
lcsh:Science
Spinal cord injury
Pain Measurement
Mammals
Multidisciplinary
Morphine
Reverse Transcriptase Polymerase Chain Reaction
Animal Models
Tapentadol
Allodynia
medicine.anatomical_structure
Spinal Cord
Neurology
Hyperalgesia
Anesthesia
Vertebrates
Neuropathic pain
Cytokines
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Ketamine
Anatomy
medicine.symptom
Research Article
Nervous System Physiology
medicine.drug
Astrocyte
Gabapentin
Pain
Nerve Tissue Proteins
Research and Analysis Methods
Real-Time Polymerase Chain Reaction
Rodents
Model Organisms
Phenols
Pain Management
Animals
[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Spinal Cord Injuries
Analysis of Variance
Activating Transcription Factor 3
business.industry
lcsh:R
Organisms
Biology and Life Sciences
Correction
Spinal cord
medicine.disease
Rats
Neuroanatomy
[ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
lcsh:Q
business
Neuroscience
Zdroj: PLoS ONE
PLoS ONE, Public Library of Science, 2014, 9 (7), pp.e102027. ⟨10.1371/journal.pone.0102027⟩
PLoS ONE, 2014, 9 (7), pp.e102027. ⟨10.1371/journal.pone.0102027⟩
PLoS ONE, Vol 9, Iss 7, p e102027 (2014)
PLoS ONE, Public Library of Science, 2014, 9 (7), pp.e102027. 〈10.1371/journal.pone.0102027〉
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0102027⟩
Popis: International audience; In humans, spinal cord lesions induce not only major motor and neurovegetative deficits but also severe neuropathic pain which is mostly resistant to classical analgesics. Better treatments can be expected from precise characterization of underlying physiopathological mechanisms. This led us to thoroughly investigate (i) mechanical and thermal sensory alterations, (ii) responses to acute treatments with drugs having patent or potential anti-allodynic properties and (iii) the spinal/ganglion expression of transcripts encoding markers of neuronal injury, microglia and astrocyte activation in rats that underwent complete spinal cord transection (SCT). SCT was performed at thoracic T8–T9 level under deep isoflurane anaesthesia, and SCT rats were examined for up to two months post surgery. SCT induced a marked hyper-reflexia at hindpaws and strong mechanical and cold allodynia in a limited (6 cm 2) cutaneous territory just rostral to the lesion site. At this level, pressure threshold value to trigger nocifensive reactions to locally applied von Frey filaments was 100-fold lower in SCT-versus sham-operated rats. A marked up-regulation of mRNAs encoding ATF3 (neuronal injury) and glial activation markers (OX-42, GFAP, P264, P267, TLR4) was observed in spinal cord and/or dorsal root ganglia at T6-T11 levels from day 2 up to day 60 post surgery. Transcripts encoding the proinflammatory cytokines IL-1b, IL-6 and TNF-a were also markedly but differentially up-regulated at T6–T11 levels in SCT rats. Acute treatment with ketamine (50 mg/kg i.p.), morphine (3–10 mg/ kg s.c.) and tapentadol (10–20 mg/kg i.p.) significantly increased pressure threshold to trigger nocifensive reaction in the von Frey filaments test, whereas amitriptyline, pregabalin, gabapentin and clonazepam were ineffective. Because all SCT rats developed long lasting, reproducible and stable allodynia, which could be alleviated by drugs effective in humans, thoracic cord transection might be a reliable model for testing innovative therapies aimed at reducing spinal cord lesion-induced central neuropathic pain.
Databáze: OpenAIRE
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