Neuropsychiatry Laboratory

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

Lab members: M Bennett (head)

The cellular origins of neuropathic pain: glial cells, macrophages and cytokines

Primary supervisor: Maxwell Bennett

The fundamental problem in ameliorating neuropathic pain is to block the spontaneous action potential firing, which originates primarily from nociceptor nerve endings in the neuroma formed at the site of nerve lesion. Nociceptors have specific classes of Na+ channels which are modified following a lesion, with tetrodotoxin-sensitive channels up-regulated and insensitive ones down-regulated. The question arises as to what are the mechanisms at the lesion site that engage this transformation in Na+ channel types. There is a proliferation of glial cells (Schwann cells) and macrophages at the neuroma, which are known to release certain species of cytokines, growth factors and transmitter substances. These must engage a retrograde transport system in the injured axons, so as to signal to the nociceptor neuron's nucleus the changes in Na+ channel expression with a concomitant orthograde redistribution of these channels to the site of the neuroma. The capacity to block specific and unique components of these processes lies at the heart of achieving specific oral analgesics without gross side-effects. Of special interest in this regard is the action of lidocaine and of P2x7 receptor antagonists. This project, which is at present the subject of experimentation in our laboratory, involves a comprehensive consideration of these pathways and mechanisms.

Wall & Malzack (2005) Text Book of Pain, 5th edn, Chapter 58.
I. Nagg & C. Woolf (1996) Pain 64(1): 59-70.
M. Araujo, C. Sinnott et al., (2003) Pain 103(1-2): 21-29.
R. Amir, C. Argoff et al., (2006) Journal of Pain 7 (5 Suppl, 3): S1-S29.
G. Liu, E. Werry & M.R. Bennett (2006) Europ J Neurosci 21(1): 151-160.
G. Liu & M.R. Bennett (2003) NeuroReport 14(16): 2078-2083.

Discipline: Physiology