Biology Reference
In-Depth Information
site of SCI promotes axon regeneration and motor recovery (
Dergham et al.,
2002
). In rats, Y-27632 has been tested after intrathecal application by Alzet
minipump after T3/T4 hemisection and was found to promote regeneration
of CST fibers and to enhance the speed of recovery, but not overall BBB
outcome scores (
Fournier et al., 2003
). Another study in rats found that oral
application of Y-27632 over 10 days did not improve BBB scores signifi-
cantly (
Sung et al., 2003
). The differences in these studies highlight how
differences in dosing regimens, delivery, and analytical methods can lead
to different outcomes.
Chronic pain conditions such as hyperalgesia is a frequent complication
of SCI, and because the mechanisms are only poorly understood, it is not
known how regenerative strategies might cause maladaptive plasticity and
influence pain. A recent study with Y-27632 after dorsal rhizotomy studied
axon regeneration of serotonergic and monoaminergic axons, and the res-
olution of pain (
Ramer et al., 2004
). A model of evoked responses to cold
hyperalgesia was used to study pain recovery. Y-27632 was applied intrathe-
cally by Alzet minipump after cutting C4-T2 dorsal roots in rats. A quan-
titative immunocytochemical analysis showed that the axonal density
of serotonergic and tyrosine hydroxylase-positive axons increased in the
Y-27632-treated animals compared to intact and vehicle-treated animals.
Rhizotomy induced cold hyperalgesia, and inhibition of ROCK with
Y-27632 attenuated the pain response. In other studies, treatment with
Cethrin did not alter the allodynia response after contusion injury in rats
(
Lord-Fontaine et al., 2008
). These results are important because they
suggest that inducing regeneration by Rho or ROCK inhibition should
not increase neuropathic pain.
2.4. NSAIDs signal to Rho
Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used
worldwide, and a surprising finding from a study on amyloid regulation
in Alzheimer's disease was that some NSAIDs act as Rho inhibitors
(
Zhou et al., 2003
). Following the first report, the effect of NSAIDs on
SCI has been investigated (
Fu, Hue, & Li, 2007; Schwab et al., 2004;
Wang et al., 2009
). Ibuprofen and indomethacin, but not naproxen,
inhibit Rho and promote neurite outgrowth
in vitro
(
Fu et al., 2007
).
Subcutaneous administration of ibuprofen induces axon sprouting after
SCI and has a neuroprotective effect that correlate with improvements in
locomotion (
Wang et al., 2009
). Clinical trials in patients have not been
undertaken to see if they may be useful. SCI patients are not typically
