PhD Thesis (Neuroscience) INSERM EMI 216, Clermont 1 University, 2006
Introduction: Wind-up is a frequency-dependent increase of neuronal response during
electrical repetitive noxious stimulation of receptive field. This phenomenon is generally expressed
in spinal and trigeminal WDR neurons. It partially depends on the activation
of NMDA and NK1 receptors.
In human, wind-up is related with the temporal summation and has consequences on the perception of pain. Its functional significance is not yet clearly established.
In sensory trigeminal complex of anaesthetized rat, we aim at:
1) analysing the characteristics and function of the wind-up of trigeminal WDR neurons.
2) identifying the neural networks underlying the wind-up and
3) establishing the role of rNMDA and rNK1 in this phenomenon. We use an electrophysiological approach with extracellular recordings in the Sp5O associated with microinjections in the Sp5C. Moreover a neuroanatomical study allowed identifying networks of interneurones conveying the message since the Sp5C towards the Sp5O. 1) the wind-up of WDR neurons of the Sp5O depends on the intensity of noxious stimulation and makes it possible to improve the coding capacities of short duration noxious stimuli. In addition, we show that wind-up involves a transitory modification (approximately 2min duration) of the WDR neurons excitability. The modification of excitability generated by the wind-up is responsible only for the facilitation responses evoked by C fibres. We suggest that the increase in the central excitability generated by the wind-up and central sensitization are different phenomena.
2) wind-up depends on the activation of the local rNMDA whereas it is submitted to an inhibition mediated by the rNMDA located in the superficial layers of the Sp5C. The trigeminal model enables to show that, even at the segmentary level, there is a permanent adjustment of the amplification of the painful message.
3) finally, the development of the wind-up also depends on the activation of the rNK1 located on interneurones localised of the lamina III of the Sp5C.
To conclude, it appears that wind-up is a segmentary phenomenon allowing the coding of short duration noxious stimulations and triggered by rNK1 and rNMDA polysynaptic ways.