Retracted: Comparison of Central versus Peripheral Delivery of Pregabalin in Neuropathic Pain States

Autor: Jose A. Martinez, William H. Frey, Leah R. Hanson, Cory Toth, Manami Kasamatsu, Alma Rosales-Hernandez
Rok vydání: 2012
Předmět:
Central Nervous System
Male
Nervous system
Neurology
Pregabalin
Pharmacology
Rats
Sprague-Dawley
Diabetic Neuropathies
Ganglia
Spinal
gamma-Aminobutyric Acid
Behavior
Animal
biology
Drug Administration Routes
Immunohistochemistry
medicine.anatomical_structure
Anesthesia
Peripheral nervous system
CACNA2D1
Neuropathic pain
Molecular Medicine
Microglia
Spinal Nerve Roots
medicine.drug
medicine.medical_specialty
Calcium Channels
L-Type
Nerve root
Blotting
Western
Central nervous system
Cellular and Molecular Neuroscience
Peripheral Nervous System
medicine
Animals
RNA
Messenger
Ligation
business.industry
Reproducibility of Results
medicine.disease
Spinal cord
Retraction
Rats
Disease Models
Animal
Spinal Nerves
Anesthesiology and Pain Medicine
Peripheral neuropathy
Gene Expression Regulation
biology.protein
Neuralgia
Calcium Channels
business
Neuroscience
Zdroj: Molecular Pain
ISSN: 1744-8069
Popis: Background: Although pregabalin therapy is beneficial for neuropathic pain (NeP) by targeting the CaVα2δ-1 subunit, its site of action is uncertain. Direct targeting of the central nervous system may be beneficial for the avoidance of systemic side effects. Results: We used intranasal, intrathecal, and near-nerve chamber forms of delivery of varying concentrations of pregabalin or saline delivered over 14 days in rat models of experimental diabetic peripheral neuropathy and spinal nerve ligation. As well, radiolabelled pregabalin was administered to determine localization with different deliveries. We evaluated tactile allodynia and thermal hyperalgesia at multiple time points, and then analyzed harvested nervous system tissues for molecular and immunohistochemical changes in CaVα2δ-1 protein expression. Both intrathecal and intranasal pregabalin administration at high concentrations relieved NeP behaviors, while near-nerve pregabalin delivery had no effect. NeP was associated with upregulation of CACNA2D1 mRNA and CaVα2δ-1 protein within peripheral nerve, dorsal root ganglia (DRG), and dorsal spinal cord, but not brain. Pregabalin's effect was limited to suppression of CaVα2δ-1 protein (but not CACNA2D1 mRNA) expression at the spinal dorsal horn in neuropathic pain states. Dorsal root ligation prevented CaVα2δ-1 protein trafficking anterograde from the dorsal root ganglia to the dorsal horn after neuropathic pain initiation. Conclusions: Either intranasal or intrathecal pregabalin relieves neuropathic pain behaviours, perhaps due to pregabalin's effect upon anterograde CaVα2δ-1 protein trafficking from the DRG to the dorsal horn. Intranasal delivery of agents such as pregabalin may be an attractive alternative to systemic therapy for management of neuropathic pain states.
Databáze: OpenAIRE
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