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Monoaminergic control of the central processing of sensory stimuli in a rat model of osteoarthritis

Burnham, LJ; (2012) Monoaminergic control of the central processing of sensory stimuli in a rat model of osteoarthritis. Doctoral thesis , UCL (University College London).

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Abstract

The main symptom of osteoarthritis (OA) is chronic pain. In many cases, this pain can be explained by stimulation of sensitised nociceptors in the joint, however changes in central nociceptive processing may also feature. These studies used single-unit recordings in the deep dorsal-horn and behavioural analysis to examine whether central sensitisation and changes in descending serotonergic (5-HT) and noradrenergic (NA) inhibition are features of the monosodium iodoacetate model of OA pain. Central sensitisation was indicated by the presence of both behavioural and spinal neuronal hypersensitivity in both an early- and a late-phase of the model .The early-phase was characterised by an increased descending noradrenergic inhibition, indicated by excitatory effects from the α2-adrenoceptor antagonist atipamezole on evoked neuronal activity, which was lost in the late-phase of the model. In the late-phase, excitatory effects of the 5-HT7 receptor antagonist SB-269970 suggested an increased descending serotonergic inhibition. In each phase, systemic injection of the 5-HT/NA reuptake inhibitor milnacipran reduced behavioural and neuronal measures of central sensitisation. In naïve animals and the early-phase of the model, these effects were mediated by NA acting at spinal α2 adrenoceptors. In the late-phase, spinal α2 adrenoceptors did not contribute to the effects of milnacipran, and 5-HT acting at spinal 5-HT7 receptors was better able to explain some of this neuronal inhibition. These studies suggest central sensitisation and altered descending monoaminergic inhibition of nociceptive processing are present in this model of OA pain. Such alterations in CNS function accord with signs of central sensitisation and dysregulated descending inhibition seen in clinical studies and might foreshadow the development of pain in OA. Additionally, the use of milnacipran, whose mechanism of action comes via a modulation of descending monoaminergic inhibition, may control centrally-mediated OA pain, though the mechanisms by which it acts appears dependent on basal activity in these pathways.

Type: Thesis (Doctoral)
Title: Monoaminergic control of the central processing of sensory stimuli in a rat model of osteoarthritis
Language: English
Keywords: Osteoarthritis, pain, nociception, descending controls, monoamines, monosodium iodoacetate model, 5-ht, noradrenenaline, electrophysiology, dorsal horn
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
URI: http://discovery.ucl.ac.uk/id/eprint/1378605
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