While regeneration of some nerves has been known for a long time to be possible, particularly in pathways associated with touch and movement, it is clear that many injuries to the nervous system are followed by incomplete recovery or even increasing disability over time.
Some of these long term effects are due to the loss of access to growth factors called neurotrophins that provide essential support for adult nerve cells. We recently discovered that immune responses can be triggered by injury leading to inflammation around the damaged nerve cells. Control of inflammation may therefore allow the remaining nerve cells to survive until treatments that enable them to regenerate can be developed.
Many injured nerve cells that fail to regenerate to their original targets die. Their loss is associated with inflammation that may trigger abnormal activity in pain pathways, or can make the skin more sensitive so that stimuli like light touch produce pain. In addition, nerve cell death can lead to reorganization of the remaining connections in the brain and spinal cord. Some of the remaining nerves grow abnormally because of the accumulation of chemicals that are usually cleared by the missing pathways. These changes can be associated with the generation of stabbing or burning pain or exaggerated responses to stimulation that is normally not painful.
We are studying the changes in the nervous system that follow injury to or disease of peripheral nerves and the spinal cord. We focus on the recruitment and activation of immune cells to sites remote from the injury and the consequences for other nerve pathways. This involves quantifying the extent of nerve cell death after experimental injuries. Whether the immune cells are beneficial or detrimental is not known, but we are currently testing the link between immune cell activation and the progressive death of injured nerve cells. We are also analysing how diabetes stresses some types of nerve cell so that they die. Understanding how injury affects nerve cells helps us to understand how the normal nervous system is maintained throughout life.
We have identified (1) sites where abnormal growth of sympathetic and sensory axons after peripheral nerve injury may underlie neuropathic pain, (2) the recruitment of T-lymphocytes into sensory ganglia and the spinal cord after peripheral nerve injury, (3) an association between the mobilization of T-lymphocytes and microglia and the potential generation of neuropathic pain, (4) atrophy of disused but intact peripheral nerve fibres below a spinal cord injury, (5) greatly increased vascular responses to nerve activity below a spinal cord injury that could account for the symptoms of "autonomic dysreflexia?.