Karam, S.M.; (2007) Morphine modulation of excitatory transmission in the rat spinal cord. Doctoral thesis , University of London.

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Abstract

The transmission of painful messages from the periphery involves complex interactions between excitatory and inhibitory neurotransmitter systems in the spinal dorsal horn. The balance between these receptor events determines the level of pain transmission. Within the spinal cord, neuronal sensitization plays a key role in altering the ascending messages to the brain. Morphine, widely used in pain control, acts on inhibitory mu opioid receptors located both on small diameter primary afferent fibres and postsynaptic sites. The aim of my studies was to determine how various excitatory transmitter systems at spinal levels are modulated by morphine in rats. The activation of the receptor for substance P, the NK-1 receptor, and the NMDA receptor for glutamate, on dorsal horn neurons are thought to contribute to wind-up pain and central sensitisation underlying a number of abnormal clinical pain states. Using in vivo electrophysiological studies and behavioural measures, I have studied the relations between peripheral inputs and central sensitisation using NK-1 and NMDA receptor agonists and further used a surgical neuropathic model and investigated the actions of morphine on the neuronal activity and pain behaviours. I have also investigated NMDA receptors located on peripheral endings of sensory nerves, and found a lack of functional effects of these receptors in pathophysiological states. Finally, the role of the excitatory 5HT3 receptor was assessed using the antagonist ondansetron in the neuropathic pain model, as was the combination of morphine and ondansetron which was more effective in inhibiting some of the pain behaviour seen in neuropathic pain than ondansetron alone. The actions of morphine, at a non-sedating dose, could overcome central sensitisation, the actions of ondansetron confirm the role of descending facilitations after nerve injury and the results demonstrate how the balance between excitation and inhibition can alter the level of pain and its control.

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