Jones, K. L., Finn, D. P., Governo, R. J. M., Prior, M. J., Morris, P. G., Kendall, D. A., Marsden, C. A. and Chapman, V. (2009) Identification of discrete sites of action of chronic treatment with desipramine in a model of neuropathic pain. Neuropharmacology, 56 (2). pp. 405-413. ISSN 0028-3908Full text not available from this repository.
Tricyclic antidepressants (TCAs) are an important analgesic treatment for neuropathic pain, though the neural substrates mediating these effects are poorly understood. We have used an integrative approach combining behavioural pharmacology with functional magnetic resonance imaging (fMRI) to investigate the effects of chronic treatment with the TCA desipramine, on touch-evoked pain (mechanical allodynia) and brain regional activity in the selective spinal nerve ligation (SNL) model of neuropathic pain. SNL and sham-operated rats received once daily i.p. administration of 10 mg/kg DMI, or saline, for 14 days. Withdrawal responses to the application of a normally non-noxious (10 g) stimulus were recorded in SNL and sham-operated rats over this period. On the final day of the study, SNL and sham-operated rats received a final challenge dose of DMI (10 mg/kg i.p.) during fMRI scanning. Chronic administration of desipramine (DMI) significantly attenuated mechancial allodynia in SNL rats. DMI challenge in chronic DMI-treated neuropathic rats produced significantly greater activation of the deep mesencephalic nucleus, primary somatosensory cortex, insular cortex, medial globus pallidus, inferior colliculus, perirhinal cortex and cerebellum compared to sham-operated rats and saline controls. By contrast, the spatial pattern of brain regional activation by chronic DMI treatment in sham controls encompassed a number of other areas including those associated with learning and memory processes. These novel findings identify key brain regions implicated in the analgesic and mood altering effects associated with chronic treatment with DMI.
|Additional Information:||IDS Number: 408SC|
|Keywords:||POSITRON EMISSION TOMOGRAPHY; EXTRACELLULAR NORADRENALINE; PERIPHERAL MONONEUROPATHY; CENTRAL SENSITIZATION; THERMAL-STIMULATION; BRAIN ACTIVATION; HEAT STIMULI; NOXIOUS HEAT; RAT-BRAIN; ANTIDEPRESSANTS|
|Schools and Departments:||Brighton and Sussex Medical School > Clinical and Laboratory Investigation|
|Subjects:||R Medicine > RC Internal medicine
R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry > RC0346 Neurology. Diseases of the nervous system Including speech disorders
R Medicine > RM Therapeutics. Pharmacology
|Depositing User:||Tracey O'Gorman|
|Date Deposited:||24 Aug 2011 14:47|
|Last Modified:||17 Jun 2013 15:40|
|Google Scholar:||7 Citations|