Molecular and behavioral exploration of orofacial hypersensitivity in a model of oxaliplatin-chemotherapy induced acute neuropathy Laura POUPON, 1 ère année de thèse U1107 – Pharmacologie fondamentale et clinique de la douleur Directeur : Pr. A. Eschalier 9ème Symposium National du Réseau Recherche sur la Douleur 22 et 23 mars 2013
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Laura POUPON, 1 ère année de thèse U1107 – Pharmacologie fondamentale et clinique de la douleur
Molecular and behavioral exploration of orofacial hypersensitivity in a model of oxaliplatin-chemotherapy induced acute neuropathy. 9ème Symposium National du Réseau Recherche sur la Douleur 22 et 23 mars 2013. Laura POUPON, 1 ère année de thèse - PowerPoint PPT Presentation
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Molecular and behavioral exploration of orofacial hypersensitivity in a model of oxaliplatin-chemotherapy
induced acute neuropathy
Laura POUPON, 1ère année de thèseU1107 – Pharmacologie fondamentale et clinique de la douleur
Directeur : Pr. A. Eschalier
9ème Symposium National du Réseau Recherche sur la Douleur22 et 23 mars 2013
Oxaliplatin chemotherapy-induced neuropathy
Therapeutic effects
Adverse effects
Used in colorectal cancer chemotherapy
Inhibits DNA replication by platinum adduct formation
90% of patients develop acute neuropathy
Cold hypersensitivity
Numbness at both extracephalic and cephalic territories
Dose reduction to limit neuropathic symptoms
Cephalic territory
Extracephalic territory
Oxaliplatin (Eloxatin®)
Platinum-based antineoplasic
DRG
Cold hyperalgesia
Mechanical hypersensitivity
Existing extracephalic results in mice
Mice modelClinical symptoms
Descoeur et al., 2011
Mice ion channels transcriptional expression
Existing extracephalic results in mice
DRG
Descoeur et al., 2011
Correlation between oxaliplatin-induced cold hypersensitivity and remodelling of ion channel expression in nociceptors
Clinical symptoms
DRG
Differences between cephalic and extracephalic sensory systems
TG
C-fibers
Sensory systems
A-fibers
Caudalis
Cephalic
?
DRG
Extracephalic
Aim of the study
• Development of adapted orofacial behavioral tests
• Assessment of ion channel transcriptional plasticity at the TG level
• Genetic or pharmacological validation of ion channels as targets of interest ?
Are there behavioral and molecular differences between the cephalic and the extracephalic territories in a murine model of oxaliplatin chemotherapy-induced neuropathy
?
Material & Methods
Mice model
Single i.p. injection of oxaliplatin (6mg/kg)
Peak pain behavior at D4
Daily measures of pain scores from D0 to D4
Day
D0 D1 D2 D3 D4
Behavioral tests
Caudalis -TG
HIC(pERK)
qPCR(ion channels)
Oral cold perception in WT mice
J-3 J0 J1 J2 J3 J40
1
2
3
4
5
* *
Wat
er c
onsu
mpti
on (m
L)
Oxaliplatin
Vehicle pERK
Cold water aversion test
Vehicle Oxaliplatin 6 mg/kg
Oral cold Hypersensitivity
D4 - Caudalis
D0 D1 D2 D3 D4
3h3h 3h 3h 3h 3h
4 - 6°C
30 min0
50
100
150
200
250VehOxa
Cutaneous cold and Mechanical perception in WT mice