In sum

1
Study 1 Unilateral T13/L1 avulsion produces
sustained mechanical allodynia and may activate
glia. Unilateral T13/L1 Avulsion induced reliable
mechanical allodynia by day 14. Ipsilateral
allodynia was maintained through the remainder of
the 30 day timecourse. Mild contralateral
allodynia was reliably observed on day 21, and
remained through the end of the experiment. We
are currently processing spinal cord tissue for
immunohistochemistry in order to assess changes
in glial activation.

Facial allodynia at 24 hours
In sum We have developed a model of spinal cord
injury involving T13/L1 avulsion. This procedure
induces a progressively developing mechanical
allodynia that lasts at least 1.5 months after
surgery. This procedure is clinically relevant
given that human avulsion injuries are associated
with a high rate of chronic pain. The advantages
of the model are numerous, including (a)
avoiding behavioral confounds that necessarily
occur with paralysis associated with prior spinal
cord injury models, and (b) lack of urinary
retention and associated health issues.
Mechanical allodynia (Bigbee et al., Exp.
Neurol., 2007) has previously been observed in
ventral root avulsion models, but this is the
first time a unilateral T13/L1 dorsal root
avulsion has been used to model exaggerated pain
associated with spinal cord injury. We show here
that the avulsion of T13 and L1 dorsal rootlets
induces bilateral mechanical allodynia in the
hind paws lasting upwards of 1.5 months. This
robust allodynia is sustained beyond that induced
by rhizotomy. We show that injury at the T13 and
L1 dorsal root entry zones results in exaggerated
pain in the hind paws, which are innervated
primarily by L5 and L6. That is, we are showing
pain below the level of injury. We are currently
developing methods by which to assess exaggerated
pain at levels between the injury and hind
paws. Consistent with peripheral nerve injury
models and other spinal cord injury models, our
initial observation is that our avulsion surgery
activates glia. Classically, astrocytes gradually
become activated and sustain that level of
activation over time, thereby maintaining the
exaggerated pain state. Astrocyte activation
appears to follow this pattern in our avulsion
model. Characterization of the microglial
activation profile in our avulsion model is in
progress.   This is the first time AV411 has
been shown to reverse mechanical allodynia in an
animal model of spinal cord injury. The reversal
of allodynia by AV411 strongly points to the
involvement of glial cells in the induction and
maintenance of exaggerated pain. Future studies
will elucidate these mechanisms in hopes that
AV411 could prove to be a novel treatment option
for patients suffering from exaggerated pain
associated with spinal cord injury.
Acknowledgements We would like to thank Ken
Lynch and Nicole Crysdale for their technical
assistance. This work is supported by Craig
Center for Spinal Cord Injury Research and NIH
grants DA01542 DA022042. Contact Information
ellisal_at_colorado.edu
IL1
TNF
IL1