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Peripheral delta opioid receptors mediate duloxetine antiallodynic effect in a mouse model of neuropathic pain
- Source :
- European Journal of Neuroscience, European Journal of Neuroscience, Wiley, 2018, 48 (5), pp.2231-2246. ⟨10.1111/ejn.14093⟩
- Publication Year :
- 2018
- Publisher :
- HAL CCSD, 2018.
-
Abstract
- International audience; Peripheral delta opioid (DOP) receptors are essential for the antiallodynic effect of the tricyclic antidepressant nortriptyline. However, the population of DOP-expressing cells affected in neuropathic conditions or underlying the antiallodynic activity of antidepressants remains unknown. Using a mouse line in which DOP receptors were selectively ablated in cells expressing Nav1.8 sodium channels (DOP cKO), we established that these DOP peripheral receptors were mandatory for duloxetine to alleviate mechanical allodynia in a neuropathic pain model based on sciatic nerve cuffing. We then examined the impact of nerve cuffing and duloxetine treatment on DOP-positive populations using a knock-in mouse line expressing a fluorescent version of the DOP receptor fused with the enhanced green fluorescent protein (DOPeGFP). Eight weeks postsurgery, we observed a reduced proportion of DOPeGFP-positive small peptidergic sensory neurons (calcitonin gene-related peptide (CGRP) positive) in dorsal root ganglia and a lower density of DOPeGFP-positive free nerve endings in the skin. These changes were not present in nerve-injured mice chronically treated with oral duloxetine. In addition, increased DOPeGFP translocation to the plasma membrane was observed in neuropathic conditions but not in duloxetine-treated neuropathic mice, which may represent an additional level of control of the neuronal activity by DOP receptors. Our results therefore established a parallel between changes in the expression profile of peripheral DOP receptors and mechanical allodynia induced by sciatic nerve cuffing.
- Subjects :
- Male
0301 basic medicine
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Population
Mice, Transgenic
Nortriptyline
Antidepressive Agents, Tricyclic
Pharmacology
Calcitonin gene-related peptide
Duloxetine Hydrochloride
03 medical and health sciences
0302 clinical medicine
Ganglia, Spinal
Receptors, Opioid, delta
medicine
Animals
Receptor
education
Pain Measurement
education.field_of_study
Chemistry
General Neuroscience
Sciatic Nerve
Disease Models, Animal
030104 developmental biology
Opioid
Hyperalgesia
Peripheral nerve injury
Neuropathic pain
Neuralgia
Female
Sciatic nerve
Free nerve ending
030217 neurology & neurosurgery
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 0953816X and 14609568
- Database :
- OpenAIRE
- Journal :
- European Journal of Neuroscience, European Journal of Neuroscience, Wiley, 2018, 48 (5), pp.2231-2246. ⟨10.1111/ejn.14093⟩
- Accession number :
- edsair.doi.dedup.....17d778ab02f23a520b75a39b4978d9ab