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Uncontrolled pain continues
to be a problem for patients. Pain management after surgery is one aspect
of difficult to control acute pain. Because
most pain models have not translated well to human postoperative pain,
we have developed rodent models of postoperative pain undertaking a
translational approach to acute pain mechanisms. Thus far, the model
appears to translate the human acute pain condition well. We have performed
highly complementary behavioral, pharmacologic, neurochemical, and electrophysiological
laboratory investigations of acute postoperative pain in the rodent.
Our focus is on mechanisms for peripheral and central sensitization
caused by incisions. For example, the receptive fields of dorsal horn
neurons develop exaggerated responses to mechanical stimuli after plantar
incision. We have also established that the pharmacology of acute postoperative
pain is unique and have identified novel therapies using spinal injections
for its relief that can now be tested in humans.
Our more recent efforts have
been aimed toward determining the role of particular pain transmitting
substances like lactic acid and nerve growth factor in our experimental
incisions. We are using a varitey of techniques to assay these pain
mediators that may activate or sensitize nociceptors in several tissues.
Primary afferent fiber recordings using in vitro skin nerve preparations
indicate unique mechanisms for primary afferent sensitization. Mediators
measured in vivo that may contribute to sensitization will be studied
in vitro. Further studies using knockout mice will examine pain related
behaviors and sensitization using in vitro recording techniques.
Representative Publications:
Wu, C., Boustany, L., Liang, H., Brennan, T.J.: Nerve Growth Factor Expression after Plantar Incision in the Rat. Anesthesiology 107:128–135, 2007.
Kim, T.J., Freml, L., Park, S.S., Brennan, T.J.: Lactate Concentrations in Incisions Indicate Ischemic-Like Conditions May Contribute to Postoperative Pain. J Pain 8:59-66, 2007.
Lee, H-J, Pogatzki-Zahn, E.M., Brennan, T.J.: The Effect of the AMPA/Kainate Receptor Antagonist LY293558 in a Rat Model of Postoperative Pain. J Pain 7:768-777, 2006.
Zahn, P.K., Pogatzki-Zhan, E.M., Brennan,
T.J.: Spinal administration of MK-801 and NBQX demonstrates NMDA-independent dorsal
horn sensitization in incisional pain. Pain 114(3):499-510, 2005.
Additional
publications
Center and Program affiliations:
The
Medical Scientist Training Program
Interdisciplinary
Graduate Program in Neuroscience |
