Identification of discrete sites of action of chronic treatment with desipramine in a model of neuropathic pain.

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 0028-3908

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Abstract

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.

Item Type: Article
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 Experimental Medicine
Brighton and Sussex Medical School > Division of Medical Education
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: 22 Sep 2017 11:51
URI: http://sro.sussex.ac.uk/id/eprint/7155
Google Scholar:7 Citations
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