Neuropharmacological studies on supraspinal modulation of visceral sensory transmission.
Doctoral thesis, UCL (University College London).
Pain from internal or cutaneous structures is an unpleasant and sensory emotional experience that accompanies disease or trauma, although there is a developing awareness towards treating pain independently as a syndrome itself rather than a by-product of illness. Pain from internal organs is one of the most common reasons for seeking medical attention, and there is accordingly growing interest in pre-clinical and clinical literature to investigate the peripheral and central mechanisms of nociceptive signalling. However, the wealth of knowledge of somatic pain signalling is contrasted by a great lack of understanding of the mechanisms in visceral nociception, which produces a great challenge in successfully treating visceral pain syndromes such as functional gut disorders. The central brainstem mechanisms mediating visceral nociceptive signalling are investigated here using electrophysiological and immunohistochemistry techniques in a model of acute visceral pain, which involves colorectal distension in normal rats and in rats with acute visceral hyperalgesia. Using pharmacological antagonism of spinal 5-HT3 receptors, a descending facilitatory serotonergic drive is shown to play a role in mediating evoked visceral pain responses monitored by electromyography. Single unit electrophysiological recordings in the serotonin-rich rostral ventromedial medulla (RVM) verify that the brainstem neuronal processing of somatic and visceral stimuli differs. Manipulation of pro-nociceptive RVM ON-cells coupled with immunohistochemistry and electrophysiology reveal an important role in regulating spinal excitability to visceral stimuli. Differential brainstem processing of noxious somatic and visceral stimuli may underlie the unique lack of state-dependent actions of the neuropathic pain drug, pregabalin, in this visceral pain model, as it produces analgesic effects in animals lacking pathophysiology and in the absence of pro-nociceptive brainstem neurones. These results illustrate differences in the central processing of visceral and somatic stimuli, yet a common role for descending modulation by brainstem activity in mediating evoked pain measures partly through serotonergic facilitations. A better understanding of the mechanisms of visceral nociception can advance translational research for producing effective analgesic treatments for the variety of visceral pain disorders.
|Title:||Neuropharmacological studies on supraspinal modulation of visceral sensory transmission|
|Additional information:||Permission for digitisation not received|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Neuroscience, Physiology and Pharmacology|
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