Jerome Coste website

PhD Thesis (Neuroscience) INSERM EMI 216, Clermont 1 University, 2006 | + | PhD manuscript

Function and mechanisms of the wind-up in nociceptive trigeminal neurons

role of NMDA receptors and NK1 receptors. ≡

Introduction - Material and methods

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.

Results - Discussion

1^stpart: Wind-up caracteristics of wide dynamic range (WDR) neurons
2^ndpart: rNMDA and Wind-Up modulation
3^rdpart: rNK1 and Wind-Up modulation

Conclusion - Bibliography

Publications

2008

Coste J.Link to the article
Coste J. et al., Pain 2008
Article , Voisin DL., Miraucourt LS., Dallel R., Luccarini P. (2008) Dorsal horn NK1-expressing neurons control windup of downstream trigeminal nociceptive neurons. Pain 137(2), 340-51 [HAL Open Access: HAL
_hal-01543208

Link to HAL database] _(3/3)

Coste J.Link to the article
Coste J. et al., Cephalalgia 2008
Article , Voisin DL., Luccarini P., Dallel R. (2008) A role for wind-up in trigeminal sensory processing: intensity coding of nociceptive stimuli in the rat. Cephalalgia 28(6), 631-9 [HAL Open Access: HAL
_hal-01543129

Link to HAL database] _(2/3)

2004

Woda A.Link to the article
Woda A. et al., European Journal of Neuroscience 2004
Article , Blanc O., Voisin DL., Coste J., Molat JL., Luccarini P. (2004) Bidirectional modulation of windup by NMDA receptors in the rat spinal trigeminal nucleus. European Journal of Neuroscience 19(8), 2009-16 [HAL Open Access: HAL
_hal-01543022

Link to HAL database] _(1/3)

PhD THESIS (french version only)