Neuropsychiatry Laboratory

Lab head: Maxwell Bennett
Location: M02 - Mallet Street Campus

Lab members: M Bennett (head)

The cellular origins of central pain sensitisation II: astrocytes, microglia and cytokines

Primary supervisor: Maxwell Bennett

Cytokines can have a powerful effect onboth transmitter release as well as on the distribution and density of transmitter receptors at synapses. For example, TNFa up-regulates AMPA receptors at glutamatergic synapses and ILib depresses transmitter release. Microglia at synapses are a principal source of both TNFa and ILib and glutamate greatly enhances the release of ILib from these glial cells. In project P3 above, we discussed the role of the astrocyte - microglia network in enhancing glutamate release from nociceptor terminals and of ATP accumulation at the synapses formed by these terminals. Given that microglia migrate to sources of high ATP, these cells can release TNFa in the glutamate -ATP rich environment. This cytokine enhances nociceptor transmission through up-regulating AMPA receptors, greatly increasing the transmission in the pain pathway. The mechanisms involved in the release of both pro-inflammatory and anti-inflammatory cytokines and their actions on nociceptor transmission will be studied in this project with the aim of identifying the appropriate sites of blockade to relieve the sensitising effects of cytokines in pain transmission.

References
D. Stellwagen & R. Malenka (2006) Nature 440(2082): 1054-1059.
F. Bianco, N. Solari et al. (2005) Journal of Immunology 174(11): 7268-7277.
D. Taylor et al. (2005) Journal of Neuroscience 25(11): 2952-2964.


Discipline: Physiology
Contact: Email Maxwell Bennett