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

journal contribution
posted on 2023-06-07, 16:03 authored by K. L. Jones, D. P. Finn, Ricardo Governo, M. J. Prior, P. G. Morris, D. A. Kendall, C. A. Marsden, V. Chapman
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.

History

Publication status

  • Published

Journal

Neuropharmacology

ISSN

0028-3908

Publisher

Elsevier

Issue

2

Volume

56

Page range

405-413

Department affiliated with

  • Clinical and Experimental Medicine Publications

Notes

IDS Number: 408SC

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2011-08-24

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