Scientists in new pain pathway discovery that could help arthritis sufferers
Scientists at King’s College, London have discovered a new and potentially major pain signalling pathway in inflammatory arthritis that may open up new possibilities for pain relief.
Recent research at the Wolfson Centre for Age Related Diseases (CARD), King’s College, London, indicates the existence of a novel pathway in arthritis pain perception that is located in the spinal cord and may be blocked by drug therapy.
Now a new three-year Arthritis Research Campaign grant of £172, 916 has been awarded to the KCL team to pursue this promising line of research.
Dr Marzia Malcangio, Senior Lecturer in Cellular Biology, emphasised the need for new research approaches: “The chronic pain that accompanies rheumatoid and osteoarthritis requires careful clinical management - effective pain control is difficult to achieve but can dramatically improve the quality of life for arthritis patients,” she explained.
“Although non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics offer effective pain relief for many people, they are not without side-effects, and the withdrawal of the Cox-2 selective inhibitors removed an promising alternative pain relief option. Consequently, there is a pressing need for preclinical studies to identify new targets for analgesic therapies in this disease area.”
In joint pain, messages are sent from the inflamed joint via the nervous system to the spinal cord and then up to the higher brain centres that register pain. This research has established that in inflammatory arthritis, specialised cells in the spinal cord, called microglial cells, act as a pain relay centre, receiving input from the peripheral nerves and directing pain messages back to spinal cord neurons on their way up to the brain.
“How the nerve endings convey their pain signals across to the microglial cells is unclear,” said Dr Malcangio. “We have established a pain relay theory that has already been tested in experimental models. A molecule known as cathepsin S is released from the spinal cells and stimulates the nerve endings to produce another molecule, called fractalkine, which feeds back on the spinal cells and activates them to signal to the brain. Administering these molecules increases pain perception associated with inflammation, but blocking them prevents pain signalling.”
Further research to establish the detailed role of these molecules in models of inflammatory pain is now ongoing. Advanced behavioural and molecular biology techniques will be employed using CatS inhibitors and FKN antibodies to test the pain relay model. Determining the underlying molecular mechanisms controlling arthritic pain will lead to improved understanding of the immune component of arthritic pain and help to identify novel targets for analgesic therapies.
