In a different line of work, we have developed a new animal pain
model in based on the administration of an antibody to the GD2
which is part of an immunotherapy being used to treat pediatric
neuroblastoma. In children and rats the antibody causes a relatively
resistant, whole body pain. In rats, we went on to demonstrate with
single fiber recording that isolated peripheral nerve fibers develop
spontaneous activity and lowered mechanical thresholds following
exposure to the antibody, these effects are reversed by low dose
lidocaine. Both rats and children have pain relief with lidocaine
and with gabapentin. We are now looking at a new antibody with a point
that is less effective in activating complement, in rats this agent
also causes substantially less pain behavior.
Experiments are underway to determine is activation of the
complement cascade is in fact the major source of the pain in these
animals. Pain behavior
and axonal electrophysiological changes are mimicked by local
administration of the pro-inflammatory cytokine TNFα to the nerve trunk
or the dorsal root
ganglia (DGR). We have gone on to show that TNFα is a major
contributor to neuropathic pain both at the level of the DRG and the
spinal cord, in part,
through its activation of the MAP kinase p38. We are presently
examining activators in between TNF and p38, at both of these loci, to
help delineate the
signal transduction process by which injury leads to MAP kinase
activation, to determine if the pathway differs according to cell type
and to help discern
better pharmacological targets for pain control.
Sorkin, L.S., et al., Spinal adenosine agonist reduces c-fos and
astrocyte activation in dorsal horn of rats with adjuvant-induced
arthritis. Neurosci Lett, 2003. 340(2): p. 119-22.
Schafers, M., et al., Increased sensitivity of injured and
adjacent uninjured rat primary sensory neurons to exogenous tumor
necrosis factor-alpha after spinal nerve ligation. J Neurosci, 2003.
23(7): p. 3028-38.
Schafers, M., et al., Tumor necrosis factor-alpha induces
mechanical allodynia after spinal nerve ligation by activation of p38
MAPK in primary sensory neurons. J Neurosci, 2003. 23(7): p. 2517-21.
Jones, T.L. and L.S. Sorkin, Calcium-permeable
receptors mediate development, but not maintenance, of secondary
allodynia evoked by first-degree burn in the rat. J Pharmacol Exp Ther,
2004. 310(1): p. 223-9.
Svensson, C.I., et al., Spinal blockade of TNF blocks spinal nerve
ligation-induced increases in spinal P-p38. Neurosci Lett, 2005.
379(3): p. 209-13.
Jones, T.L. and L.S. Sorkin, Activated PKA and PKC, but not
CaMKIIalpha, are required for AMPA/Kainate-mediated pain behavior in the
thermal stimulus model. Pain, 2005. 117(3): p. 259-70.
- B.S. in Psychobiology(1975) and Ph.D.in Psychobiology (1983), University of Michigan
- Post-doctoral fellowships
- Bill Willis, University of Texas Medical Branch (UTMB), Galveston
- Fernando Cervero, Bristol University, United Kingdom
- Research Associate at UTMB (1987-91)
- Assistant Professor, then Professor in Anesthesiology and member of the Neurosciences Group (1991- present)
Dr. Sorkin is a past member of the board of directors of the
American Pain Society and the research committee of the International
for the Study of Pain. She currently serves on the editorial board
for the journals Pain and The Journal of Pain and is the pain mechanisms
section editor for the journal, Neuroscience.