Neuropsychiatry Laboratory

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

Lab members: M Bennett (head)

The cellular origins of central pain sensitisation I: the astrocyte - microglia network

Primary supervisor: Maxwell Bennett

The spontaneous action potential firing in nociceptor neurons generated at the site of a neuroma after a lesion causes neuropathic pain. However, after the lesion has healed on-going pain is often still experienced. There is evidence that an astrocyte - microglia cell network in the dorsal horn, at the site of nociceptor synapses, could mediate this process of sensitisation. Nociceptor nerve terminals, firing spontaneous bursts, release both glutamate and substance P which we have shown trigger the release of large amounts of ATP from astrocytes. In addition, microglia migrate to the site of such terminals, where they are in turn triggered to release ATP in response to glutamate release from the terminals. The very large ATP concentrations that ensue are such as to be able to activate P2x7 receptor-forming pores in the microglia, leading to the unregulated release of ATP and cytokines. This ATP/cytokine soup can then activate P2x receptors on the nociceptor terminals to greatly enhance the release of glutamate and ATP under even mild impulse traffic. The resulting positive feedback network ensures an increase in nociceptor transmission in the pain pathway that becomes independent of any elevated action potential firing in the terminals. The experimental and theoretical aspects of this pain sensitisation will be examined in this project.

M. Tsuda, K, Inoue,& M. Slater (2005) Trends in Neurosciences 28(2): 101-107.
A. Abdipranoto, G. Liu, E. Werry & M.R. Bennett (2003) NeuroReport 14(17): 2177-2181.
G. Liu, A. Kalous, E. Werry & M.R. Bennett (2006) Molecular Pharmacology (Epub).
E. Werry, G. Liu & M.R. Bennett (2006) Journal of Neurochemistry (Epub).

Discipline: Physiology