Timothy J. Brennan, MD, PhD

Portrait
Professor of Anesthesia - Acute Pain and Regional Anesthesia
Professor of Pharmacology

Contact Information

Primary Office: 6418 JCP
200 Hawkins Drive
Iowa City, IA 52242
319-356-2633

Lab: 3000 ML
25 South Grand Avenue
Iowa City, IA 52242
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Education

BS, Natural Science, St. John's University
PhD, Pharmacology, University of Texas Health Center
MD, Medicine, University of Oklahoma Health and Science Center

Postdoctoral Fellow, Physiology, University of Oklahoma Health Sciences Center
Internship, Medicine, University of Oklahoma Health Sciences Center
Resident, Anesthesiology, University of Virginia Health Sciences Center

Education/Training Program Affiliations

Interdisciplinary Graduate Program in Neuroscience, Interdisciplinary Graduate Program in Translational Biomedicine, Medical Scientist Training Program

Research Summary

Our goal has been to improve the management of postoperative pain in surgical patients. We recognized that there was a significant gap between basic science pain research and clinical acute postoperative pain management that should be explored. We examine how surgical incisions cause pain using preclinical animal models. Having developed a model for measuring pain behaviors caused by incision in rats, we examine the key process producing clinical pain states- sensory neuron sensitization; the conversion of normal, non-painful sensory stimuli to pain eliciting responses. We utilize in vivo and in vitro neurophysiologic methods to examine the sensitization process and the resulting behavioral phenomena at the level of the primary afferent neuron, as well as the spinal cord dorsal horn. Extracellular in vivo dorsal horn cells are recorded in anesthetized rats and combined with behavioral pharmacology. The results of the spinal cord dorsal horn experiments describe why the AMPA-kainate receptor system is critical for expression of pain behaviors after incision. An area of research to develop in the future is the clinical use of spinal and epidural non-NMDA receptor antagonists for use in humans and clinical pain states. Our second area of emphasis is the peripheral sensitization process caused by incision. In vivo single fiber primary afferent recordings continue to be utilized. Recordings of pain transmitting fibers will be studied in vitro using organ sensory nerve preparations like skin nerve and muscle nerve studies. We will attempt to develop these preparations in mouse tissues to take advantage of knockout animals.

Publications

Bayman, E. O., Brennan, T. J. (2018). In reply. (Vols. 128). (1), pp. 225. Anesthesiology. PMID: 29232230.

Eisenach, J. C., Brennan, T. J. (2018). Pain after surgery. Pain, 159(6), 1010-1011. PMID: 29768304.

Bayman, E. O., Parekh, K. R., Keech, J. C. & Brennan, T. J. (2018). Predictors of Moderate-to-Severe Acute Pain after Video-Assisted Thoracoscopic Surgery.

Kent, M. L., Tighe, P. J., Belfer, I., Brennan, T. J., Bruehl, S., Brummett, C. M., Buckenmaier, 3rd, C. C., Buvanendran, A., Cohen, R. I., Desjardins, P., Edwards, D., Fillingim, R., Gewandter, J., Gordon, D. B., Hurley, R. W., Kehlet, H., Loeser, J. D., Mackey, S., McLean, S. A., Polomano, R., Rahman, S., Raja, S., Rowbotham, M., Suresh, S., Schachtel, B., Schreiber, K., Schumacher, M., Stacey, B., Stanos, S., Todd, K., Turk, D. C., Weisman, S. J., Wu, C., Carr, D. B., Dworkin, R. H. & Terman, G. (2017). The ACTTION-APS-AAPM Pain Taxonomy (AAAPT) multidimensional approach to classifying acute pain conditions. Pain Medicine, 18(5), 947-58. PMID: 28482098.

Bayman, E. O., Lennertz, R. & Brennan, T. J. (2017). Pain-related limitations in daily activities following thoracic surgery in a United States population. Pain Physician, 20(3), E367-E378. PMID: 28339436.

Kent, M. L., Tighe, P. J., Belfer, I., Brennan, T. J., Bruehl, S., Brummett, C. M., Buckenmaier, 3rd, C. C., Buvanendran, A., Cohen, R. I., Desjardins, P., Edwards, D., Fillingim, R., Gewandter, J., Gordon, D. B., Hurley, R. W., Kehlet, H., Loeser, J. D., Mackey, S., McLean, S. A., Polomano, R., Rahman, S., Raja, S., Rowbotham, M., Suresh, S., Schachtel, B., Schreiber, K., Schumacher, M., Stacey, B., Stanos, S., Todd, K., Turk, D. C., Weisman, S. J., Wu, C., Carr, D. B., Dworkin, R. H. & Terman, G. (2017). The ACTTION-APS-AAPM Pain Taxonomy (AAAPT) multidimensional approach to classifying acute pain conditions. The Journal of Pain, 18(5), 479-89. PMID: 28495013.

Bayman, E. O., Parekh, K. R., Keech, J., Selte, A. & Brennan, T. J. (2017). A prospective study of chronic pain after thoracic surgery. Anesthesiology, 126(5), 938-51. PMID: 28248713.

Sugiyama, D., Kang, S. & Brennan, T. J. (2017). Muscle reactive oxygen species (ROS) contribute to post-incisional guarding via the TRPA1 receptor. PloS One, 12(1), e0170410. PMID: 28103292.

Bayman, E. O., Parekh, K. R., Keech, J. & Brennan, T. J. (2017). Response to "VATS vs. thoracotomy regarding postoperative chronic pain". (Vols. 9). (12), pp. E1151-3. Journal of thoracic disease. PMID: 29313852.

Bayman, E. O., Parekh, K. R., Keech, J. & Brennan, T. J. (2017). A prospective study of predictors of chronic pain after thoracic surgery.

Bayman, E. O., Parekh, K. R., Keech, J. & Brennan, T. J. (2017). Response to "Editorial on pain following thoracic surgery". (Vols. 9). (12), pp. E1154-5. Journal of thoracic disease. PMID: 29313846.

Bayman, E. O., Parekh, K. R., Keech, J. & Brennan, T. J. (2017). Association of preoperative expected pain with acute pain after video-assisted thorascopic surgery.

Sugiyama, D., Kang, S., Arpey, N., Arunakul, P., Usachev, Y. M. & Brennan, T. J. (2017). Hydrogen peroxide induces muscle nociception via transient receptor potential ankyrin 1 receptors. Anesthesiology, 127(4), 695-708. PMID: 28640016.

Chou, R., Gordon, D. B., de Leon-Casasola, O. A., Rosenberg, J. M., Bickler, S., Brennan, T. J., Carter, T., Cassidy, C. L., Chittenden, E. H., Degenhardt, E., Griffith, S., Manworren, R., McCarberg, B., Montgomery, R., Murphy, J., Perkal, M. F., Suresh, S., Sluka, K., Strassels, S., Thirlby, R., Viscusi, E., Walco, G. A., Warner, L., Weisman, S. J. & Wu, C. L. (2016). Management of postoperative pain: a clinical practice guideline from the American Pain Society, the American Society of Regional Anesthesia and Pain Medicine, and the American Society of Anesthesiologists' Committee on Regional Anesthesia, Executive Committee, and Administrative Council. The Journal of Pain, 17(2), 131-57. PMID: 26827847.

Gordon, D. B., de Leon-Casasola, O. A., Wu, C. L., Sluka, K. A., Brennan, T. J. & Chou, R. (2016). Research gaps in practice guidelines for acute postoperative pain management in adults: findings from a review of the evidence for an American Pain Society Clinical Practice Guideline. The Journal of Pain, 17(2), 158-66. PMID: 26719073.

Reddy, C. G., Dalm, B. D., Flouty, O. E., Gillies, G. T., Howard, 3rd, M. A. & Brennan, T. J. (2016). Comparison of conventional and kilohertz frequency epidural stimulation in patients undergoing trialing for spinal cord stimulation: clinical considerations. World Neurosurgery, 88, 586-91. PMID: 26585728.

(2016). The Danish questionnaire for pain after thoracic surgery in a United States population.

Brennan, T. J., Lennertz, R. C. & Kang, S. (2016). Are opioid-tolerant patients resistant to local anesthetic nerve blockade?: we need more information. Anesthesiology, 125(4), 625-6. PMID: 27428824.

Miller, J. W., Reddy, C. G., Wilson, S., Abode-Iyamah, K. O., DeVries-Watson, N. A., Fredericks, D. C., Gillies, G. T., Johnson, M. D., Brennan, T. J. & Howard III, M. A. (2016). Spinal cord stimulation in sheep models of chronic neuropathic pain and spinal cord injury-induced spasticity.

Wibbenmeyer, L., Eid, A., Kluesner, K., Heard, J., Zimmerman, B., Kealey, G. P. & Brennan, T. J. (2015). An evaluation of factors related to postoperative pain control in burn patients. Journal of Burn Care & Research, 36(5), 580-6. PMID: 26335109.

Dalm, B. D., Reddy, C. G., Howard, M. A., Kang, S. & Brennan, T. J. (2015). Conditioned place preference and spontaneous dorsal horn neuron activity in chronic constriction injury model in rats. Pain, 156(12), 2562-71. PMID: 26584420.

Marian, A. A., Ranganath, Y., Bayman, E. O., Senasu, J. & Brennan, T. J. (2015). A comparison of 2 ultrasound-guided approaches to the saphenous nerve block: adductor canal versus distal transsartorial: a prospective, randomized, blinded, noninferiority trial. Regional Anesthesia and Pain Medicine, 40(5), 623-30. PMID: 26110441.

Miller, J. W., Reddy, C. G., Wilson, S., Dalm, B. D., Safayi, S., Shivapour, S. K., Adobe-Iyamah, K., Viljoen, S., Fredericks, D. C., Gibson-Corley, K. N., Grosland, N. M., Jerath, N. U., Stoner, K., Reale, R., Oya, H., Jeffery, N. D., Brennan, T. J., Gillies, G. T. & Howard III, M. A. (2015). Spinal cord stimulation in an ovine model of neuorpathic pain measured through Von Frey filaments, gait analysis, and dorsal horn recordings.

Vaid-Pinyard, S., Masters, J. & Brennan, T. J. (2015). The novel use of bilateral popliteal sciatic catheters for analgesia to facilitate healing from nonfreezing cold-induced injury (immersion foot).

Miller, J. W., Reddy, C. G., Wilson, S., Dalm, B. D., Safayi, S., Adobe-Iyamah, K., Shivapour, S. K., Viljoen, S., Fredericks, D. C., Gibson-Corley, K. N., Grosland, N. M., Jerath, N. U., Stoner, K., Reale, R., Oya, H., Jeffery, N. D., Brennan, T. J., Gillies, G. T. & Howard III, M. A. (2015). Spinal cord stimulation in an ovine model of neuorpathic pain measured through Von Frey filaments, gait analysis, and dorsal horn recordings.

Sugiyama, D., Kang, S., Gu, H. & Brennan, T. J. (2015). Possible contribution of TRPA1 to capsaicin-induced analgesia in deep tissue pain.

Kang, S., Sugiyama, D., Gu, H. & Brennan, T. J. (2015). Hydrogen peroxide (H2O2) induces pain via TRPA1 receptors in deep tissue.

Brennan, T. J., Kang, S. (2014). Is second pain worse than the first?. (Vols. 155). (1), pp. 2-3. Pain. PMID: 24141225.

Brennan, T. J. (2014). Effects of Damage to Skin on Nociceptive Pathways. In O. Walder-Smith , L. Arendt-Nielsen , D. Yarnitsky , K. C. Vissers (Eds.) Postoperative Pain, Science and Clinical Practice. Washington, DC: IASP Press.

Xu, J., Brennan, T. J. (2014). Incision-Induced Nociceptive Effects in Deep Tissue. In T. Graven-Nielsen , L. Arendt-Nielsen (Eds.) Musculoskeletal Pain: Basic Mechanisms and Implications. Washington, DC: IASP Press.

Mamet, J., Klukinov, M., Yaksh, T. L., Malkmus, S. A., Williams, S., Harris, S., Manning, D. C., Taylor, B. K., Donahue, R. R., Porreca, F., Xie, J. Y., Oyarzo, J., Brennan, T. J., Subieta, A., Schmidt, W. K. & Yeomans, D. C. (2014). Single intrathecal administration of the transcription factor decoy AYX1 prevents acute and chronic pain after incisional, inflammatory, or neuropathic injury. Pain, 155(2), 322-33. PMID: 24145208.

Dalm, B. D., Viljoen, S. V., Dahdaleh, N. S., Reddy, C. G., Brennan, T. J., Oya, H., Wilson, S., Safayi, S., Jeffrey, N. D., Gillies, G. T. & Howard III, M. A. (2014). Revisiting intradural spinal cord stimulation: an introduction to a novel intradural spinal cord stimulation device. Innovative Neurosurgery, 2(1-4), 13-20. DOI: 10.1515/ins-2014-0005.

Bayman, E. O., Brennan, T. J. (2014). Incidence and severity of chronic pain at 3 and 6 months after thoracotomy: meta-analysis. The Journal of Pain, 15(9), 887-97. PMID: 24968967.

Kehlet, H., Edwards, R. R. & Brennan, T. J. (2014). Persistent Postoperative Pain: Pathogenic Mechanisms and Preventive Strategies. In S. N. Raja , C. L. Sommer (Eds.) Pain 2014 Refresher Courses: 15th World Congress on Pain. Washington, DC: IASP Press.

Kang, S., Chae, W. & Brennan, T. J. (2014). A rat model of phrenic motor inhibition after upper abdominal surgery.

Bayman, E. O., Brennan, T. J. (2014). No change on the incidence of chronic pain after thoracotomy for three decades.

Kang, S., Sugiyama, D. & Brennan, T. J. (2014). Effect of Damage to Skin on Nociceptive Pathways. In O. Wilder-Smith , L. Arendt-Nielsen & D. Yarnitsky , K. C. Vissers (Eds.) Postoperative Pain – Science and Clinical Practice. (2), pp. 5-16. Seattle, WA: International Association for the Study of Pain (IASP) Press.

Shutov, L. P., Warwick, C. A., Gupte, R. P., Shepherd, A. J., Brennan, T. J., Clark, D. D., Mohapatra, D. P. & Usachev, Y. M. (2013). Complement C5a produces nociceptive sensitization via TRPV1 in mouse.

Kang, S., Brennan, T. J. (2013). Plantar Incision Model: a Preclinical Model of Postoperative Pain. In H. Handwerker , L. Arendt-Nielsen (Eds.) Pain Models: Translational Relevance and Applications. Washington, DC: IASP Press.

Ueda, K., Shields, B. E. & Brennan, T. J. (2013). Transesophageal echocardiography: a novel technique for guidance and placement of an epidural catheter in infants. Anesthesiology, 118(1), 219-22. PMID: 23165474.

Kido, K., Gautam, M., Benson, C. J., Gu, H. & Brennan, T. J. (2013). Effect of deep tissue incision on pH responses of afferent fibers and dorsal root ganglia innervating muscle. Anesthesiology, 119(5), 1186-97. PMID: 23732174.

Dalm, B. D., Brennan, T. J., Elahi, F., Howard III, M. A. & Reddy, C. G. (2013). Successful conservative management of an intrathecal catheter-associated inflammatory mass. The Spine Journal, 13(11), 1708-9. PMID: 24176809.

Kang, S., Lee, D., Theusch, B. E., Arpey, C. J. & Brennan, T. J. (2013). Wound hypoxia in deep tissue after incision in rats. Wound Repair and Regeneration, 21(5), 730-9. PMID: 23926943.

Yalamuri, S. M., Brennan, T. J. & Spofford, C. M. (2013). Neuropeptide Y is analgesic in rats after plantar incision. European Journal of Pharmacology, 698(1-3), 206-12. PMID: 23123350.

Flouty, O., Oya, H., Kawasaki, H., Wilson, S., Reddy, C. G., Jeffery, N. D., Brennan, T. J., Gibson-Corley, K. N., Utz, M., Gillies, G. T. & Howard III, M. A. (2012). A new device concept for directly modulating spinal cord pathways: initial in vivo experimental results. Physiological Measurement, 33(12), 2003-15. PMID: 23151433.

Buys, M. J., Brennan, T. J. (2012). A novel fracture pain model in the rat.

Wilson, S., Howard, M. A., Rossen, J. D., Brennan, T. J., Dalm, B. D., Dahdaleh, N. S., Utz, M. & Gillies, G. T. (2012). Pulsatile spinal cord surrogate for intradural neuromodulation studies. Journal of Medical Engineering & Technology, 36(1), 22-5. PMID: 22188575.

Spofford, C. M., Brennan, T. J. (2012). Gene expression in skin, muscle, and dorsal root ganglion after plantar incision in the rat. Anesthesiology, 117(1), 161-72. PMID: 22617252.

Arunakul, P., Brennan, T. J. (2012). Nerve blockade using capsaicin and local anesthetic reduces pain behaviors caused by plantar incision.

Dudley-Cash, A. I., Brennan, T. J. (2012). The effect of low concentration capsaicin infiltration on acute pain from incision.

Kang, S., Jang, J. H., Price, M. P., Gautam, M., Benson, C. J., Gong, H., Welsh, M. J. & Brennan, T. J. (2012). Simultaneous disruption of mouse ASIC1a, ASIC2 and ASIC3 genes enhances cutaneous mechanosensitivity. PloS One, 7(4), e35225. PMID: 22506072.

Arunakul, P., Brennan, T. J. (2012). Combined capsaicin and local anesthetic nerve blockade inhibits postoperative pain behaviors in rat plantar incision model.

Brennan, T. J. (2011). Pathophysiology of postoperative pain. (Vols. 152). (3 Suppl), pp. S33-40. Pain. PMID: 21232860.

Manion, S. C., Brennan, T. J. (2011). Thoracic epidural analgesia and acute pain management. (Vols. 115). (1), pp. 181-8. Anesthesiology. PMID: 21606825.

Spofford, C. M., Mohan, S., Kang, S., Jang, J. H. & Brennan, T. J. (2011). Evaluation of leukemia inhibitory factor (LIF) in a rat model of postoperative pain. The Journal of Pain, 12(7), 819-32. PMID: 21729793.

Howard III, M. A., Utz, M., Brennan, T. J., Dalm, B. D., Viljoen, S., Kanwal, J. K. & Gillies, G. T. (2011). Biophysical attributes of an in vitro spinal cord surrogate for use in developing an intradural neuromodulation system. Journal of Applied Physics, 110, 074701. DOI: 10.1063/1.3642976.

Brennan, T. J., Kang, S. & Xu, J. (2011). The Neurobiology of Incisional Pain. In G. A. Mashour , R. Lydic (Eds.) Neuroscientific Foundations of Anesthesiology. pp. 141-52. New York, NY: Oxford University Press.

Xu, J., Brennan, T. J. (2011). The pathophysiology of acute pain: animal models. (Vols. 24). (5), pp. 508-14. Current Opinion in Anaesthesiology. PMID: 21841478.

Jang, J. H., Liang, D., Kido, K., Sun, Y., Clark, D. J. & Brennan, T. J. (2011). Increased local concentration of complement C5a contributes to incisional pain in mice. Journal of Neuroinflammation, 8, 80. PMID: 21736743.

Howard III, M. A., Utz, M., Brennan, T. J., Dalm, B. D., Viljoen, S., Jeffery, N. D. & Gillies, G. T. (2011). Intradural approach to selective stimulation in the spinal cord for treatment of intractable pain: design principles and wireless protocol. Journal of Applied Physiology, 110, 044702. DOI: 10.1063/1.3626469.

Dudley-Cash, A. I., Subieta, A. R. & Brennan, T. J. (2011). The differential effect of low dose capsaicin infiltration on incisional pain.

Kido, K., Brennan, T. J. (2011). The effect of amiloride on pH response of incised muscle afferents.

Spofford, C. M., Brennan, T. J. (2011). Evaluation of a new model of postoperative pain.

Arunakul, P., Brennan, T. J. (2011). Effect of capsaicin and local anesthetic nerve blockade on pain behaviors caused by plantar incision.

Kang, S., Jang, J. H., Subieta, A. R., Price, M. P., Welsh, M. J. & Brennan, T. J. (2011). A role of ASICs in guarding pain behaviors and C-fiber chemosensitivity in postoperative pain.

Yalamuri, S. M., Brennan, T. J. & Spofford, C. M. (2011). Intrathecal administration of neuropeptide Y is analgesic after plantar incision.

Kang, S., Wu, C., Banik, R. K. & Brennan, T. J. (2010). Effect of capsaicin treatment on nociceptors in rat glabrous skin one day after plantar incision. Pain, 148(1), 128-40. PMID: 19948377.

Pulley, S. C., Spofford, C. M. & Brennan, T. J. (2010). Continuous cervical paravertebral catheter knot. Journal of Clinical Anesthesia, 22(2), 135-8. PMID: 20304358.

Jang, J. H., Clark, D. J., Li, X., Yorek, M. S., Usachev, Y. M. & Brennan, T. J. (2010). Nociceptive sensitization by complement C5a and C3a in mouse. Pain, 148(2), 343-52. PMID: 20031321.

Brennan, T. J. (2010). Acute pain: pathophysiology and clinical implications. M. Rosenblatt (Eds.) (Vols. 38). pp. 8-14. Schaumburg, IL: American Society of Anesthesiologists. DOI: 10.1097/ASA.0b013e3181e9561f.

Xu, J., Gu, H. & Brennan, T. J. (2010). Increased sensitivity of group III and group IV afferents from incised muscle in vitro. Pain, 151(3), 744-55. PMID: 20888124.

Gu, H., Brennan, T. J. (2010). Skin plus deep tissue incision enhances dorsal horn neuron activity during rat plantar muscle contraction.

Kang, S., Lee, D., Theusch, B. E. & Brennan, T. J. (2010). Tissue hypoxia in subcutaneous and deep muscle tissues after incision in rats.

Jang, J. H., Kido, K. & Brennan, T. J. (2010). Activation and sensitization of nociceptors by complement C5a in incised mouse skin.

Xu, J., Brennan, T. J. (2010). Guarding pain and spontaneous activity of nociceptors after skin versus skin plus deep tissue incision. Anesthesiology, 112(1), 153-64. PMID: 19996955.

Spofford, C. M., Mohan, S., Kang, S., Jang, J. & Brennan, T. J. (2010). Characterization of Leukemia Inhibitory Factor (LIF) after plantar incision.

Xu, J., Gu, H. & Brennan, T. J. (2010). Sensitization of group III and IV afferents from incised muscle in vitro.

Wu, C., Xu, J., Kang, S., Spofford, C. M. & Brennan, T. J. (2010). Animal Models of Postoperative Pain. In C. Ma , J. Zhang (Eds.) Animal Models of Pain. pp. 181-200. Springer.

Kumar, A. B., Brennan, T. J. (2009). Pain assessment, sedation, and analgesic administration in the intensive care unit. (Vols. 111). (6), pp. 1187-8. Anesthesiology. PMID: 19934859.

Spofford, C. M., Brennan, T. J. (2009). P2X4 Receptor incision in skin and muscle after plantar incision in the rat.

Xu, J., Brennan, T. J. (2009). Incision increases spontaneous activity, chemosensitivity, mechanical, and heat response of muscle nociceptors in vitro.

Spofford, C. M., Ashmawi, H., Subieta, A., Buevich, F., Moses, A., Baker, M. & Brennan, T. J. (2009). Ketoprofen produces modality-specific inhibition of pain behaviors in rats after plantar incision. Anesthesia and Analgesia, 109(6), 1992-9. PMID: 19923531.

Jang, J. H., Kang, S., Price, M. P., Welsh, M. H. & Brennan, T. J. (2009). Response of cutaneous mechanosensitive afferents to the combination of acid/lactate/ATP in ASIC triple KO mouse in vitro.

Brennan, T. J., Gu, H. (2009). Skin plus deep tissue incision enhanced dorsal horn activity during the rat plantar muscle static contraction.

Spofford, C. M., Brennan, T. J. (2009). Gene regulation in muscle after plantar incision.

Mohan, S., Spofford, C. M. & Brennan, T. J. (2009). Expression profile of leukemia inhibitory factor (LIF) and leukemia inhibitory factor receptor in a rat model of postoperative pain.

Kang, S., Brennan, T. J. (2009). Changes in tissue oxygen tension after incision in the rat.

Spofford, C. M., Brennan, T. J. (2009). Plantar incision differentially regulates gene expression in rat muscle.

Udeh, C., Brennan, T. J. (2009). Perioperative medicine in the United States. Perioperative Medizin, 1(4), 211-6. DOI: 10.1016/j.periop.2009.05.001.

Hamalainen, M. M., Subieta, A., Arpey, C. & Brennan, T. J. (2009). Differential effect of capsaicin treatment on pain-related behaviors after plantar incision. The Journal of Pain, 10(6), 637-45. PMID: 19386553.

Banik, R. K., Brennan, T. J. (2009). TrpV1 mediates spontaneous firing and heat sensitization of cutaneous primary afferents after plantar incision. Pain, 141(1-2), 41-51. PMID: 19010598.

Wu, C., Erickson, M. A., Xu, J., Wild, K. D. & Brennan, T. J. (2009). Expression profile of nerve growth factor after muscle incision in the rat. Anesthesiology, 110(1), 140-9. PMID: 19104181.

Borgeat, A., Brennan, T. J., Eisenach, J. C., Hemmings, H. C., Isono, S., Kersten, J. R., Kochs, E., Riou, B. & Warner, D. S. (2009). 2009 in Review: Advancing medicine in anesthesiology. Anesthesiology, 111, 1192-6. DOI: 10.1097/ALN.0b013e3181c1879b.

Brennan, T. J. (2009). Incisional/Postoperative Pain. In M. D. Binder , N. Hirokawa , U. Windhorst (Eds.) Encyclopedia of Neuroscience. pp. 1941-5. Springer. DOI: 10.1007/978-3-540-29678-2_2405.

Xu, J., Richebe, P. & Brennan, T. J. (2009). Separate groups of dorsal horn neurons transmit spontaneous activity and mechanosensitivity one day after plantar incision. European Journal of Pain, 13(8), 820-8. PMID: 19081275.

Xu, J., Brennan, T. J. (2009). Comparison of skin incision vs. skin plus deep tissue incision on ongoing pain and spontaneous activity in dorsal horn neurons. Pain, 144(3), 329-39. PMID: 19527922.

Kang, S., Brennan, T. J. (2009). Chemosensitivity and mechanosensitivity of nociceptors from incised rat hindpaw skin. Anesthesiology, 111(1), 155-64. PMID: 19512876.

Shontz, R., Karuparthy, V., Temple, R. & Brennan, T. J. (2009). Prevalence and risk factors predisposing to coagulopathy in patients receiving epidural analgesia for hepatic surgery. Regional Anesthesia and Pain Medicine, 34(4), 308-11. PMID: 19574863.

Wu, C., Erickson, M., Xu, J., Wild, K. D. & Brennan, T. J. (2008). Role of muscle NGF in incisional pain.

Brennan, T. J., Gavaa, N. & Wu, C. (2008). Effect of AMG0347, a Transient Receptor Potential Type V1 receptor antagonist, and morphine on pain behavior after plantar incision.

Eisenach, J. C., Borgeat, A., Bosnjak, Z. J., Brennan, T. J., Kersten, J. R., Kochs, E., Lerman, J., Warner, D. S. & Wiener-Kronish, J. P. (2008). 2008 in Review: Advancing medicine in anesthesiology. Anesthesiology, 109(6), 962-72. PMID: 19034092.

Xu, L., Price, M., Banik, R., Subieta, A. R., Welsh, M. & Brennan, T. J. (2008). Mechanical responses of cutaneous afferents in ASIC triple KO mice.

Kang, S., Brennan, T. J. (2008). In vitro acid sensitivity of nociceptors from incised rat hindpaw skin.

Xu, J., Brennan, T. J. (2008). In vitro characterization of group III and IV primary afferents from incised muscle.

Jang, J. H., Brennan, T. J. (2008). Complement C5a activates and sensitizes cutaneous nociceptors in mouse hairy skin.

Spofford, C. M., Brennan, T. J. (2008). Gene upregulation in rat skin, muscle, and dorsal root ganglion after plantar incision.

Xu, L., Price, M. J., Banik, R. K., Welsh, M. & Brennan, T. J. (2008). Mechanical responses of cutaneous afferents in ASIC triple KO mice.

Brennan, T. J., Spofford, C. M. (2008). Differential effect of ketoprofen on pain behavior after plantar incision.

Cameron, D. M., Brennan, T. J. & Gebhart, G. F. (2008). Hind paw incision in the rat produces long-lasting colon hypersensitivity. The Journal of Pain, 9(3), 246-53. PMID: 18088562.

Wu, C., Gavva, N. R. & Brennan, T. J. (2008). Effect of AMG0347, a transient receptor potential type V1 receptor antagonist, and morphine on pain behavior after plantar incision. Anesthesiology, 108(6), 1100-8. PMID: 18497612.

Eisenach, J. C., Borgeat, A., Bosnjak, Z. J., Brennan, T. J., Kersten, J. R., Kochs, E. F. & Wiener-Kronish, J. P. (2008). 2007 in Review: A dozen steps forward in Anesthesiology. Anesthesiology, 108(1), 149-55. PMID: 18156893.

Gordon, D., Inturrisi, C. E., Greensmith, J. E., Brennan, T. J., Goble, L. & Kerns, R. D. (2008). Perioperative pain management in the opioid-tolerant individual. The Journal of Pain, 9(5), 383-7. PMID: 18337186.

Banik, R. K., Brennan, T. J. (2008). Sensitization of primary afferents to mechanical and heat stimuli after incision in a novel in vitro mouse glabrous skin-nerve preparation. Pain, 138(2), 380-91. PMID: 18316159.

Brennan, T. J., Xu, J. & Subieta, A. R. (2007). In vivo dorsal horn neuron activity in skin versus skin plus deep tissue incision in the rat hindpaw.

Xu, J., Subieta, A. R. & Brennan, T. J. (2007). In vivo nociceptor activity and pain behaviors in skin versus skin plus deep tissue incision in the rat hindpaw.

Kang, S., Banik, R. K. & Brennan, T. J. (2007). Effect of subcutaneous capsaicin on mechanosensitive afferents in rat glabrous skin one day after plantar incision.

Wu, C., Kang, S. & Brennan, T. J. (2007). Differential effect of subcutaneous capsaicin injection on pain behaviors and afferent fiber immunoreactivity after plantar incision.

Eisenach, J. C., Brennan, T. J. (2007). Anesthesiology and the press. (Vols. 107). (1), pp. 8. Anesthesiology. PMID: 17585209.

Jin, H. C., Keller, A. J., Jung, J. K., Subieta, A. & Brennan, T. J. (2007). Epidural tezampanel, an AMPA/kainate receptor antagonist, produces postoperative analgesia in rats. Anesthesia and Analgesia, 105(4), 1152-9, table of contents. PMID: 17898404.

Wu, C., Boustany, L., Liang, H. & Brennan, T. J. (2007). Nerve growth factor expression after plantar incision in the rat. Anesthesiology, 107(1), 128-35. PMID: 17585224.

Pogatzki-Zahn, E. M., Zahn, P. K. & Brennan, T. J. (2007). Postoperative pain--clinical implications of basic research. Best Practice & Research: Clinical Anaesthesiology, 21(1), 3-13. PMID: 17489216.

Costa-Bartlett, V., Price, M. P., Hattori, T., Burnes, L. A., Subieta, A. R., Brennan, T. J., Sluka, K. A., Benson, C. J. & Welsh, M. J. (2007). ASIC3 overexpression enhances thermal sensitivity in transgenic mice.

Kim, T. J., Freml, L., Park, S. S. & Brennan, T. J. (2007). Lactate concentrations in incisions indicate ischemic-like conditions may contribute to postoperative pain. The Journal of Pain, 8(1), 59-66. PMID: 16949881.

Xu, L., Wu, C., Xu, T. & Brennan, T. J. (2007). NGF expression in muscle after plantar incision.

Banik, R. K., Woo, Y. C., Park, S. S. & Brennan, T. J. (2006). Strain and sex influence on pain sensitivity after plantar incision in the mouse. Anesthesiology, 105(6), 1246-53. PMID: 17122588.

Whyte, D. G., Brennan, T. J. & Johnson, A. K. (2006). Thermoregulatory behavior is disrupted in rats with lesions of the anteroventral third ventricular area (AV3V). Physiology & Behavior, 87(3), 493-9. PMID: 16487986.

Ness, T. J., Brennan, T. J. (2006). Chapter 22: Sensory Systems. In H. C. Hemmings JR , P. M. Hopkins (Eds.) Foundations of Anesthesia. (2), pp. 257-266. Elsevier. DOI: 10.1016/B978-0-323-03707-5.50028-0.

Lee, H., Pogatzki-Zahn, E. M. & Brennan, T. J. (2006). The effect of the AMPA/kainate receptor antagonist LY293558 in a rat model of postoperative pain. The Journal of Pain, 7(10), 768-77. PMID: 17018337.

Jin, H. C., Brennan, T. J. (2006). Epidural NGX 424, an AMPA-kainate receptor antagonist produces analgesia in rats after plantar incision.

Wu, C., Subieta, A. R. & Brennan, T. J. (2006). Effect of capsaicin intradermal pre-injection on skin incision pain in rats.

Zahn, P. K., Pogatzki-Zahn, E. M. & Brennan, T. J. (2005). Spinal administration of MK-801 and NBQX demonstrates NMDA-independent dorsal horn sensitization in incisional pain. Pain, 114(3), 499-510. PMID: 15777875.

Brennan, T. J., Zahn, P. K. & Pogatzki-Zahn, E. M. (2005). Mechanisms of incisional pain. Anesthesiology Clinics of North America, 23(1), 1-20. PMID: 15763408.

Richebé, P., Rathmell, J. P. & Brennan, T. J. (2005). Immediate early genes after pulsed radiofrequency treatment: neurobiology in need of clinical trials. (Vols. 102). (1), pp. 1-3. Anesthesiology. PMID: 15618777.

Banik, R. K., Subieta, A. R., Wu, C. & Brennan, T. J. (2005). Increased nerve growth factor after rat plantar incision contributes to guarding behavior and heat hyperalgesia. Pain, 117(1-2), 68-76. PMID: 16061324.

Brennan, T. J., Kehlet, H. (2005). Preventive analgesia to reduce wound hyperalgesia and persistent postsurgical pain: not an easy path. (Vols. 103). (4), pp. 681-3. Anesthesiology. PMID: 16192759.

Brennan, T. J. (2005). Incisional sensitivity and pain measurements: dissecting mechanisms for postoperative pain. (Vols. 103). (1), pp. 3-4. Anesthesiology. PMID: 15983447.

Banik, R. K., Brennan, T. J. (2004). Spontaneous discharge and increased heat sensitivity of rat C-fiber nociceptors are present in vitro after plantar incision. Pain, 112(1-2), 204-13. PMID: 15494202.

Page, A. J., Brierley, S. M., Martin, C. M., Martinez-Salgado, C., Wemmie, J. A., Brennan, T. J., Symonds, E., Omari, T., Lewin, G. R., Welsh, M. J. & Blackshaw, L. A. (2004). The ion channel ASIC1 contributes to visceral but not cutaneous mechanoreceptor function. Gastroenterology, 127(6), 1739-47. PMID: 15578512.

Leonard, P. A., Arunkumar, R. & Brennan, T. J. (2004). Bradykinin antagonists have no analgesic effect on incisional pain. Anesthesia and Analgesia, 99(4), 1166-72, table of contents. PMID: 15385370.

Brennan, T. J. (2004). Chapter 5: A rat model of postoperative pain. pp. Unit 5.34. Current Protocols in Pharmacology. PMID: 22294121.

Woo, Y. C., Park, S. S., Subieta, A. R. & Brennan, T. J. (2004). Changes in tissue pH and temperature after incision indicate acidosis may contribute to postoperative pain. Anesthesiology, 101(2), 468-75. PMID: 15277931.

Zahn, P. K., Subieta, A., Park, S. S. & Brennan, T. J. (2004). Effect of blockade of nerve growth factor and tumor necrosis factor on pain behaviors after plantar incision. The Journal of Pain, 5(3), 157-63. PMID: 15106128.

Pogatzki, E. M., Niemeier, J. S., Sorkin, L. S. & Brennan, T. J. (2003). Spinal glutamate receptor antagonists differentiate primary and secondary mechanical hyperalgesia caused by incision. Pain, 105(1-2), 97-107. PMID: 14499425.

Berde, C. B., Brennan, T. J. & Raja, S. N. (2003). Opioids: more to learn, improvements to be made. (Vols. 98). (6), pp. 1309-12. Anesthesiology. PMID: 12766636.

Pogatzki, E. M., Niemeier, J. S. & Brennan, T. J. (2002). Persistent secondary hyperalgesia after gastrocnemius incision in the rat. European Journal of Pain, 6(4), 295-305. PMID: 12161095.

Hämäläinen, M. M., Gebhart, G. F. & Brennan, T. J. (2002). Acute effect of an incision on mechanosensitive afferents in the plantar rat hindpaw. Journal of Neurophysiology, 87(2), 712-20. PMID: 11826040.

Pogatzki, E. M., Gebhart, G. F. & Brennan, T. J. (2002). Characterization of Adelta- and C-fibers innervating the plantar rat hindpaw one day after an incision. Journal of Neurophysiology, 87(2), 721-31. PMID: 11826041.

Brennan, T. J. (2002). Frontiers in translational research: the etiology of incisional and postoperative pain. (Vols. 97). (3), pp. 535-7. Anesthesiology. PMID: 12218516.

Zahn, P. K., Sluka, K. A. & Brennan, T. J. (2002). Excitatory amino acid release in the spinal cord caused by plantar incision in the rat. Pain, 100(1-2), 65-76. PMID: 12435460.

Pogatzki, E. M., Urban, M. O., Brennan, T. J. & Gebhart, G. F. (2002). Role of the rostral medial medulla in the development of primary and secondary hyperalgesia after incision in the rat. Anesthesiology, 96(5), 1153-60. PMID: 11981156.

Jarvis, M. F., Burgard, E. C., McGaraughty, S., Honore, P., Lynch, K., Brennan, T. J., Subieta, A., Van Biesen, T., Cartmell, J., Bianchi, B., Niforatos, W., Kage, K., Yu, H., Mikusa, J., Wismer, C. T., Zhu, C. Z., Chu, K., Lee, C. H., Stewart, A. O., Polakowski, J., Cox, B. F., Kowaluk, E., Williams, M., Sullivan, J. & Faltynek, C. (2002). A-317491, a novel potent and selective non-nucleotide antagonist of P2X3 and P2X2/3 receptors, reduces chronic inflammatory and neuropathic pain in the rat. Proceedings of the National Academy of Sciences of the United States of America, 99(26), 17179-84. PMID: 12482951.

Zahn, P. K., Pogatzki, E. M. & Brennan, T. J. (2002). Mechanisms for pain caused by incisions. Regional Aesthesia and Pain Medicine, 27(5), 514-6. PMID: 12373702.

Pogatzki, E. M., Vandermeulen, E. P. & Brennan, T. J. (2002). Effect of plantar local anesthetic injection on dorsal horn neuron activity and pain behaviors caused by incision. Pain, 97(1-2), 151-61. PMID: 12031788.

Von Bergen, N. H., Subieta, A. & Brennan, T. J. (2002). Effect of intrathecal non-NMDA EAA receptor antagonist LY293558 in rats: a new class of drugs for spinal anesthesia. Anesthesiology, 97(1), 177-82. PMID: 12131120.

Price, M. P., McIlwrath, S. L., Xie, J., Cheng, C., Qiao, J., Tarr, D. E., Sluka, K. A., Brennan, T. J., Lewin, G. R. & Welsh, M. J. (2001). The DRASIC cation channel contributes to the detection of cutaneous touch and acid stimuli in mice. Neuron, 32(6), 1071-83. PMID: 11754838.

Pogatzki, E. M., Zahn, P. K. & Brennan, T. J. (2000). Lumbar catheterization of the subarachnoid space with a 32-gauge polyurethane catheter in the rat. European Journal of Pain, 4(1), 111-3. PMID: 10833561.

Zahn, P. K., Brennan, T. J. (2000). Preemptive analgesia: moving beyond conventional strategies and confusing terminology. The Journal of Pain, 1(2), 77-84. DOI: 10.1016/S1526-5900(00)90090-7.

Brennan, T. J., Zahn, P. K. (2000). Effect of intrathecal ACEA-1021 in a rat model for postoperative pain. The Journal of Pain, 1(4), 279-84. PMID: 14622611.

Brennan, T. J., Taylor, B. K. (2000). Analgesic treatment before incision compared with treatment after incision provides no improvement in postoperative pain relief. The Journal of Pain, 1(2), 96-8. DOI: 10.1016/S1526-5900(00)90094-4.

Vandermeulen, E. P., Brennan, T. J. (2000). Alterations in ascending dorsal horn neurons by a surgical incision in the rat foot. Anesthesiology, 93(5), 1294-302; discussion 6A. PMID: 11046219.

Price, M. P., Lewin, G. R., McIlwrath, S. L., Cheng, C., Xie, J., Heppenstall, P. A., Stucky, C. L., Mannsfeldt, A. G., Brennan, T. J., Drummond, H. A., Qiao, J., Benson, C. J., Tarr, D. E., Hrstka, R. F., Yang, B., Williamson, R. A. & Welsh, M. J. (2000). The mammalian sodium channel BNC1 is required for normal touch sensation. (Vols. 407). (6807), pp. 1007-11. Nature. PMID: 11069180.

Pogatzki, E. M., Zahn, P. K. & Brennan, T. J. (2000). Effect of pretreatment with intrathecal excitatory amino acid receptor antagonists on the development of pain behavior caused by plantar incision. Anesthesiology, 93(2), 489-96. PMID: 10910500.

Zahn, P. K., Brennan, T. J. (1999). Primary and secondary hyperalgesia in a rat model for human postoperative pain. Anesthesiology, 90(3), 863-72. PMID: 10078689.

Brennan, T. J. (1999). Postoperative models of nociception. ILAR Journal, 40(3), 129-36. PMID: 11406691.

Zahn, P. K., Brennan, T. J. (1999). Incision-induced changes in receptive field properties of rat dorsal horn neurons. Anesthesiology, 91(3), 772-85. PMID: 10485789.

Zahn, P. K., Brennan, T. J. (1998). Lack of effect of intrathecally administered N-methyl-D-aspartate receptor antagonists in a rat model for postoperative pain. Anesthesiology, 88(1), 143-56. PMID: 9447867.

Zahn, P. K., Brennan, T. J. (1998). Intrathecal metabotropic glutamate receptor antagonists do not decrease mechanical hyperalgesia in a rat model of postoperative pain. Anesthesia and Analgesia, 87(6), 1354-9. PMID: 9842826.

Zahn, P. K., Umali, E. & Brennan, T. J. (1998). Intrathecal non-NMDA excitatory amino acid receptor antagonists inhibit pain behaviors in a rat model of postoperative pain. Pain, 74(2-3), 213-23. PMID: 9520236.

Brennan, T. J. (1998). AMPA/kainate receptor antagonists as novel analgesic agents. (Vols. 89). (5), pp. 1049-51. Anesthesiology. PMID: 9821991.

Zahn, P. K., Gysbers, D. & Brennan, T. J. (1997). Effect of systemic and intrathecal morphine in a rat model of postoperative pain. Anesthesiology, 86(5), 1066-77. PMID: 9158356.

Zahn, P. K., Brennan, T. J. (1997). Physiologic and pharmacologic bases of anesthesiology. (Vols. 86). pp. 751. Schaumburg, IL: Anesthesiology.

Brennan, T. J. (1997). Point of View: Postoperative pain control after lumbar spine fusion: Patient-controlled analgesia versus continuous epidural analgesia. (Vols. 22). (16), pp. 1896-7. Lebanon, New Hampshire: Spine.

Wedel, D. J., White, P. F., Brennan, T. J. & Sandler, A. (1997). Workshop on how to perform clinical outcome studies. University of Münster, Münster, Germany, May 22-23, 1997. Anesthesiology, 87(4), 1021-2. PMID: 9357923.

Brennan, T. J., Umali, E. F. & Zahn, P. K. (1997). Comparison of pre- versus post-incision administration of intrathecal bupivacaine and intrathecal morphine in a rat model of postoperative pain. Anesthesiology, 87(6), 1517-28. PMID: 9416737.

Brennan, T. J., Vandermeulen, E. P. & Gebhart, G. F. (1996). Characterization of a rat model of incisional pain. Pain, 64(3), 493-501. PMID: 8783314.

Brennan, T. J. (1995). Nalmefene: a long-acting injectable opioid antagonist. The Medical Letter on Drugs and Therapeutics, 37(960), 97-8. PMID: 7565300.

Demun, E. M., Redd, J. L., Buchanan, K. A., Brennan, T. J., Rowlingson, J. C., Himel, H. N., Morgan, R. F. & Edlich, R. F. (1993). Reflex sympathetic dystrophy after a minor electric shock. The Journal of Emergency Medicine, 11(4), 393-6. PMID: 8228100.

Chandler, M. J., Brennan, T. J., Garrison, D. W., Kim, K. S., Schwartz, P. J. & Foreman, R. D. (1993). A mechanism of cardiac pain suppression by spinal cord stimulation: implications for patients with angina pectoris. European Heart Journal, 14(1), 96-105. PMID: 8432300.

Bolser, D. C., Hobbs, S. F., Chandler, M. J., Ammons, W. S., Brennan, T. J. & Foreman, R. D. (1991). Convergence of phrenic and cardiopulmonary spinal afferent information on cervical and thoracic spinothalamic tract neurons in the monkey: implications for referred pain from the diaphragm and heart. Journal of Neurophysiology, 65(5), 1042-54. PMID: 1869904.

Hobbs, S. F., Oh, U. T., Brennan, T. J., Chandler, M. J., Kim, K. S. & Foreman, R. D. (1990). Urinary bladder and hindlimb stimuli inhibit T1-T6 spinal and spinoreticular cells. The American Journal of Physiology, 258(1 Pt 2), R10-20. PMID: 2301620.

Brennan, T. J., Oh, U. T., Hobbs, S. F., Garrison, D. W. & Foreman, R. D. (1989). Urinary bladder and hindlimb afferent input inhibits activity of primate T2-T5 spinothalamic tract neurons. Journal of Neurophysiology, 61(3), 573-88. PMID: 2709101.

Chandler, M. J., Garrison, D. W., Brennan, T. J. & Foreman, R. D. (1989). Effects of chemical and electrical stimulation of the midbrain on feline T2-T6 spinoreticular and spinal cell activity evoked by cardiopulmonary afferent input. Brain Research, 496(1-2), 148-64. PMID: 2804627.

Brennan, T. J., Oh, U. T., Girardot, M. N., Ammons, W. S. & Foreman, R. D. (1987). Inhibition of cardiopulmonary input to thoracic spinothalamic tract cells by stimulation of the subcoeruleus-parabrachial region in the primate. Journal of the Autonomic Nervous System, 18(1), 61-72. PMID: 3819316.

Haywood, J. R., Ball, N. A., Lifschitz, M. D. & Brennan, T. J. (1987). Contribution of AV3V region in anephric NaCl-induced hypertension in the rat. The American Journal of Physiology, 252(3 Pt 2), F536-42. PMID: 3826392.

Girardot, M., Brennan, T. J., Martindale, M. E. & Foreman, R. D. (1987). Effects of stimulating the subcoeruleus-parabrachial region on the non-noxious and noxious responses of T1-T5 spinothalamic tract neurons in the primate. Brain Research, 409(1), 19-30. PMID: 3034377.

Haywood, J. R., Brennan, T. J. (1985). Interactions of Gamma-Aminobutyric Acid with Osmotic-Stimulated Vasopressin Release. In R. W. Schrier (Eds.) Vasopressin. pp. 417-24. New York, NY: Raven Press.

Haywood, J. R., Brennan, T. J. & Hinojosa, C. (1985). Neurohumoral mechanisms of sodium-dependent hypertension. Federation Proceedings, 44(8), 2393-9. PMID: 2859221.

Brennan, T. J., Haywood, J. R. (1985). GABAergic inhibition of hypertonic saline-induced vasopressin-dependent hypertension. The Journal of Pharmacology and Experimental Therapeutics, 233(3), 663-71. PMID: 4009486.

Brennan, T. J., Morris, M. & Haywood, J. R. (1984). GABA agonists inhibit central sodium-induced vasopressin-dependent increases in arterial pressure. European Journal of Pharmacology, 103(3-4), 223-34. PMID: 6489442.

Brennan, T. J., Morris, M. & Haywood, J. R. (1984). GABA agonists inhibit the vasopressin-dependent pressor effects of central angiotensin II. Neuroendocrinology, 39(5), 429-36. PMID: 6514131.

Brennan, T. J., Haywood, J. R. (1983). GABA inhibition of central angiotensin II and hypertonic CSF pressor responses. Brain Research, 267(2), 261-9. PMID: 6871675.

Brennan, T. J., Haywood, J. R. & Ticku, M. K. (1983). GABA receptor binding and hemodynamic responses to ICV GABA in adult spontaneously hypertensive rats. Life Sciences, 33(8), 701-9. PMID: 6136888.

Thyagarajan, R., Brennan, T. & Ticku, M. K. (1983). GABA and benzodiazepine binding sites in spontaneously hypertensive rat. European Journal of Pharmacology, 93(3-4), 127-36. PMID: 6315448.