The London Pain Consortium: Key discoveries

LPC-affiliated researchers have been instrumental in several new discoveries that have rapidly advanced pain research.

Research by Professor John Wood's laboratory at University College London identified a crucial protein in peripheral pain-sensing receptors that helps to explain the cause of an inherited chronic pain disorder, erythromalgia, which creates a constant and painful burning sensation.

Mouse studies by Dr Mohammad Nassar in 2004 - then a London Pain Consortium postdoctoral student at Professor Wood's laboratory - revealed that the sodium channel Nav1.7 was essential for many aspects of the pain system: one mutation caused hyperactivity, where even the slightest stimulation led to enhanced pain, while a knockout of the Nav1.7 gene produced mice unable to feel pain at all.

The findings guided clinical researchers to the same mutation in humans, which also tied in with patient studies being conducted by Dr David Bennett at King's College London.

Mother and daughter, Janet and Lucy, have experienced chronic pain in their feet most of their adult lives. In this film, they describe their pain, the ordeal of daily life, and we join them as they visit the clinic of Dr David Bennett.

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The discovery of Nav1.7, and the fact that humans without the gene are otherwise normal, has provided a promising target for future analgesic drugs free from side effects. In addition, the tools developed during the discovery have helped pain researchers in the LPC and the wider scientific community - particularly a line of transgenic 'knockout mice' that enable scientists to delete specific genes in damage- sensing neurons, helping them to understand which are key to pain signalling.

Elsewhere, the research of Professor Steve McMahon and Dr David Bennett at King's College London has revealed insights into the fundamental role of nerve growth factor as an important pain mediator. This has led to several clinical trials of new analgesic drugs targeting this mechanism, three of which have shown promising results in patients so far.

Professor McMahon has also developed animal models of pain and a wide variety of techniques with which to study them, including electrophysiological, behavioural, anatomical and histochemical methods. His laboratory is studying models of pain associated with diseases such as cancer and osteoarthritis. Meanwhile, Professor Irene Tracey at the Oxford Centre for Functional MRI of the Brain (part of the LPC) is conducting brain-imaging studies to try to understand the experience of pain in people with and without chronic pain conditions.

References

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