Noradrenergic fiber sprouting and altered transduction in neuropathic prefrontal cortex

Autor: Philippe Séguéla, Geraldine Longo, Alfredo Ribeiro-da-Silva, Maria Zamfir, Steven Cordeiro Matos
Rok vydání: 2017
Předmět:
0301 basic medicine
Male
medicine.medical_specialty
Histology
Patch-Clamp Techniques
Barium Compounds
Prefrontal Cortex
Dopamine beta-Hydroxylase
In Vitro Techniques
Membrane Potentials
03 medical and health sciences
Norepinephrine
0302 clinical medicine
Adrenergic Agents
Nerve Fibers
Chlorides
Neuromodulation
Internal medicine
HCN channel
medicine
Animals
Rats
Long-Evans
Prefrontal cortex
Visual Cortex
Neurons
biology
General Neuroscience
Chronic pain
Pain Perception
Nerve injury
medicine.disease
Electric Stimulation
Rats
Disease Models
Animal
030104 developmental biology
Peripheral neuropathy
Endocrinology
medicine.anatomical_structure
Hyperalgesia
Peripheral nerve injury
Neuropathic pain
biology.protein
Neuralgia
Anatomy
medicine.symptom
Psychology
Neuroscience
030217 neurology & neurosurgery
Zdroj: Brain structurefunction. 223(3)
ISSN: 1863-2661
Popis: Functional changes in hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels have been shown to contribute to medial prefrontal (mPFC) hyperexcitability after peripheral nerve injury. A reduction in the open probability of these neuronal channels might be relevant since this can enhance membrane input resistance and synaptic summation. However, the molecular mechanisms underlying neuropathy-associated alterations in HCN channel activity remain elusive. Using the spared nerve injury model of neuropathic pain in Long-Evans rats, we first discovered a significant increase in noradrenergic innervation within the mPFC of nerve-injured compared to control animals. Patch-clamp recordings in layer II/III pyramidal neurons of the mPFC revealed that adrenoceptors, primarily the α2 subtype, can modulate the voltage-dependent activation of HCN channels and the abnormal prefrontal excitability following peripheral neuropathy. Additionally, microinfusions of the α2 adrenoceptor agonist clonidine in the mPFC of neuropathic rats provided analgesic effects, indicating the behavioral significance for this noradrenergic pathway in manifestations of the chronic pain state. Taken together, our results provide insights into the role of cortical catecholaminergic neuromodulation in neuropathic pain and suggest that altered noradrenergic transduction may play a major role in the HCN channel dysfunction and pyramidal hyperactivity observed in several chronic pain conditions.
Databáze: OpenAIRE
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