Persisting neurones switch
to a ‘survivor’ phenotype and the expression of
hundreds of genes
8,9 is changed to compensate for the loss or
diminution of target-derived neurotrophic factors,
10 and in
order to regrow their axons across the site of the injury and
back into the periphery. Proximal changes, such as synaptic
reorganisation in the cortex
11–13 and spinal cord, occur
upstream of axotomised first-order motor and sensory neurones,
and may influence the functional outcome months or even years
later.
14–16 Distal to the injury, a series of molecular and cellular events,
some simultaneous, others consecutive, and collectively called
Wallerian degeneration, is triggered throughout the distal nerve
stump and within a small reactive zone at the tip of the proximal
stump (Fig. 2
).
17–19
T-cells, neutrophils and macrophages infiltrate the site of
an injury within two days;
40–42 the neutrophil response
is very limited in both time and extent. Within hours, endoneurial
levels of the early inflammatory cytokines, tumour necrosis
factor alpha (TNF-
) and interleukin (IL)-1
, secreted mostly
by Schwann cells, start to increase in the distal nerve stump.
Within days, this network has been amplified by cytokines, chemokines
and other bioactive molecules released by recruited macrophages,
mast cells and activated endothelial cells.
43–51 Some
of these molecules influence the behaviour of the Schwann cells
(e.g. macrophage derived IL-1 regulates nerve growth factor
(NGF) synthesis by Schwann cells)
52 and others may play a role
in the generation and/or maintenance of neuropathic pain.
Pathway selection.
One of the most important determinants of a satisfactory functional
outcome is the accuracy of target re-innervation. If axons degenerate
without rupture of the basal laminae which surround each Schwann
tube, e.g. in an ischaemic or compressive lesion, then the axon
sprouts are unlikely to be misrouted upon resolution of the
underlying pathology. That is not the case after traumatic injuries
in which a nerve is physically disrupted. Whether the resulting
proximal and distal nerve stumps are sutured without tension,
143–145 or are bridged by an intervening graft, the axon sprouts which
emerge from the proximal stump are bound to encounter unfamiliar
Schwann tubes. Most sprouts, once they have negotiated the site
of the suture, will remain within the endoneurium of the distal
stump or graft. Those nearest to the periphery of the proximal
stump may either escape with their Schwann cells into the epineurium
through breaches in the damaged perineurium, or they may grow
ectopically between the layers of the perineurium. In both situations
their behaviour may produce a painful neuroma.
http://web.jbjs.org.uk/cgi/content/full/87-B/10/1309
http://www.sympatix.fi/blog/?lang=en_
