Retracted: Comparison of central versus peripheral delivery of pregabalin in neuropathic pain states

Molecular Pain

Cory C Toth³  William H Frey²  Leah R Hanson¹  Alma Rosales-Hernandez³  Manami Kasamatsu³  Jose A Martinez³ 

[1] Alzheimer's Research Center, Regions Hospital, and HealthPartners Research Foundation, St. Paul, MN, USA;Department of Pharmaceutics, University of Minnesota, Minneapolis, MN, USA;Department of Clinical Neurosciences and the University of Calgary, Calgary, AB, Canada

关键词: spinal nerve ligation;    diabetic peripheral neuropathy;    pregabalin;    neuropathic pain;   

Others  :  865563
DOI  :  10.1186/1744-8069-8-3

 received in 2011-05-27, accepted in 2012-01-11,  发布年份 2012

【 摘 要 】

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.

【 授权许可】

   
2012 Martinez et al; licensee BioMed Central Ltd.

【 图 表 】

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