Pain Lab

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Research

Aims and Concepts
The aim of our research is to investigate the mechanisms underlying chronic neuropathic pain following nervous system injury, focusing on the involvement of immune cells and their mediators in neuropathic pain.
Nervous system injury such as peripheral nerve injury and spinal cord injury often results in chronic neuropathic pain characterized by spontaneous pain and increases in pain sensitivity. Neuropathic pain is relatively common with an estimated prevalence of 5-7% in the general population and is among the most disabling and expensive burdens in western countries including Australia. During the past two decades, an important focus of pain research has been the study of the mechanisms underlying chronic pain, in particular at the neuronal level. Recently, however, it has become clear that non-neuronal cells including immune and glial cells strongly influence neuronal functions, and thus play a crucial role in neuropathic pain caused by damage to the nervous system. Our current research is in the neuroimmune processes which underlie neuropathic pain. We are working on how immune cells, glial cells and inflammatory mediators contribute to the pain arising from nerve damage (Fig.1 and Fig. 2). The research is centered on the types of cells which are likely to be involved (e.g. macrophages, lymphocytes, microglia) and the inflammatory mediators which may be responsible (e.g. pro-inflammatory cytokines).



Fig. 1 – Peripheral nerve injury induces activation of resident immune cells as well as recruitment of inflammatory cells to the nerve. Injury of a peripheral nerve initiates an inflammatory response in which mast cells, neutrophils, macrophages and T cells are recruited and activated, Schwann cell dedifferentiate and all release their mediators such as pro-inflammatory cytokines and contribute to neuropathic pain (Moalem G & Tracey DJ. Brain Res Brain Res Rev 51, 240-264; 2006).


Fig. 2 – Peripheral nerve injury induces glial activation in the dorsal horn of the spinal cord. Injury to a peripheral nerve initiates increased release of neurotransmitters such as glutamate, substance P and ATP from the central terminals of primary afferents. These neurotransmitters can activate both second order neurones and glia, which produce and release inflammatory mediators including pro-inflammatory cytokines (such as TNF and IL-1â), glutamate (Glu), prostaglandins (PGs) and nitric oxide (NO). These agents are then capable of sensitising dorsal horn neurones, thereby contributing to neuropathic pain (Moalem G & Tracey DJ. Brain Res Brain Res Rev 51, 240-264; 2006).

Methods
We use animal models of neuropathic pain to investigate the neuro-immune crosstalk in the injured nervous system. Experimental techniques include: Animal surgery (e.g., peripheral nerve injury), animal behavior studies (measuring withdrawal latency to thermal stimuli using a plantar analgesia meter for paw stimulation, and measuring withdrawal threshold to mechanical stimuli using an electronic von Frey anesthesiometer and Randall-Selitto analgesymeter), histological work (confocal microscopy and image analysis), cell culture, and electrophysiology using the technique of in vitro threshold tracking to measure axonal excitability.

Staff

Cristina Kim (Research Assistant)
Faith Hill (Honours Student)

Research Grants

Present

NHMRC Project Grant (ID # 568637) “The role of proinflammatory interleukin-17 (IL-17) and IL-17 producing T cells in neuropathic pain"	Moalem-Taylor G.	2009-2011
NSW OSMR Career Development Fellowship Research Grant “Immunomodulation of neuropathic pain due to peripheral nerve injury or spinal cord injury”	Moalem-Taylor G.	2010-2012

Past

Rothschild Fellowship to post doctoral position awarded by Yad Hanadiv	Moalem-Taylor G.	2000- 2001
The Vice-Chancellor's Postdoctoral Research Fellowship, UNSW “Neuropathic pain behaviour induced by T cell-mediated autoimmune disease of the peripheral nervous system”	Moalem-Taylor G.	2004-2007
UNSW Faculty Research Grant Program, "Axonal receptors - could they contribute to inflammatory or neuropathic pain"	Tracey DJ (CIA) & Moalem-Taylor G. (CIB)	2004
UNSW Faculty Research Grant for Early Career Researchers "The effect of preconditioning lesion on chronic neuropathic pain due to peripheral nerve injury"	Moalem-Taylor G.	2005
UNSW Goldstar Award “Modulation of immune responses in regulating chronic pain following nerve injury”	Moalem-Taylor G. (CIA) & Tracey DJ (CIB)	2006
NHMRC Project Grant (ID # 400947) “Does the complement system contribute to neuropathic pain?"	Moalem-Taylor G. (CIA) & Tracey DJ (CIB)	2006-2008
UNSW Faculty Research Grant Program, "Does IL-17 play a role in neuropathic pain?"	Moalem-Taylor G.	2008
UNSW Faculty of Medicine, Post Doctoral Small Grant Scheme "Preconditioning nerve lesion inhibits neuropathic pain in rats"	Moalem-Taylor G.	2008

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Publications

• G1. Hirschberg DL*, Moalem G*, He J, Mor F, Cohen IR & Schwartz M. Accumulation of passively transferred primed T cells independently of their antigen specificity following central nervous system trauma. (*Equal contributors) J Neuroimmunol 89: 88-96 (1998).
• G2. Monsonego A, Mizrahi T, Eitan S, Moalem G, Bardos H, Adany R & Schwartz M. Factor XIIIa as a nerve-associated transglutaminase. Faseb J 12: 1163-1171 (1998).
• G3. Moalem G, Leibowitz-Amit R, Yoles E, Mor F, Cohen IR & Schwartz M. Autoimmune T cells protect neurons from secondary degeneration after central nervous system axotomy. Nat Med 5: 49-55 (1999).
• G4. Ophir R, Moalem G, Pecht M, Shashoua M, Rashid G, Ben-Efraim S, Trainin N, Burstein Y & Keisari Y. THF-gamma 2-mediated reduction of pulmonary metastases and augmentation of immunocompetence in C57BL/6 mice bearing B16-melanoma. J Immunother 22: 103-113 (1999).
• G5. Moalem G, Monsonego A, Shani Y, Cohen IR & Schwartz M. Differential T cell response in central and peripheral nerve injury: connection with immune privilege. Faseb J 13: 1207-1217 (1999).
• G6. Schwartz M, Moalem G, Leibowitz-Amit R & Cohen IR. Innate and adaptive immune responses can be beneficial for CNS repair. REVIEW. Trends Neurosci 22: 295-299 (1999).
• G7. Schwartz M, Cohen I, Lazarov-Spiegler O, Moalem G & Yoles E. The remedy may lie in ourselves: prospects for immune cell therapy in central nervous system protection and repair. REVIEW. J Mol Med 77: 713-717 (1999).
• G8. Hauben E, Nevo U, Yoles E, Moalem G, Agranov E, Mor F, Akselrod S, Neeman M, Cohen IR & Schwartz M. Autoimmune T cells as potential neuroprotective therapy for spinal cord injury. Lancet 355: 286-287 (2000).
• G9. Moalem G, Yoles E, Leibowitz-Amit R, Muller-Gilor S, Mor F, Cohen IR & Schwartz M. Autoimmune T cells retard the loss of function in injured rat optic nerves. J Neuroimmunol 106: 189-197 (2000).
• G10. Hauben E, Butovsky O, Nevo U, Yoles E, Moalem G, Agranov E, Mor F, Leibowitz-Amit R, Pevsner E, Akselrod S, Neeman M, Cohen IR & Schwartz M. Passive or active immunization with myelin basic protein promotes recovery from spinal cord contusion. J Neurosci 20: 6421-6430 (2000).
• G11. Moalem G, Gdalyahu A, Shani Y, Otten U, Lazarovici P, Cohen IR & Schwartz M. Production of neurotrophins by activated T cells: implications for neuroprotective autoimmunity. J Autoimmun 15: 331-345 (2000).
• G12. Schwartz M & Moalem G. Beneficial immune activity after CNS injury: prospects for vaccination. REVIEW. J Neuroimmunol 113, 185-192 (2001).
• G13. Moalem G, Xu K & Yu L. T lymphocytes play a role in neuropathic pain following peripheral nerve injury in rats. Neuroscience 129: 767-777 (2004).
• G14. Moalem G, Grafe P & Tracey DJ. Chemical mediators enhance the excitability of unmyelinated sensory axons in normal and injured peripheral nerve of the rat. Neuroscience 134: 1399-1411 (2005).
• G15. Lang PM*, Moalem-Taylor G*, Tracey D, Bostock H & Grafe P. Activity-dependent modulation of axonal excitability in unmyelinated peripheral rat nerve fibers by the 5-HT(3) serotonin receptor. (*Equal contributors) J Neurophysiol 96: 2963-2971 (2006).
• G16. Moalem G & Tracey DJ. Immune and inflammatory mechanisms in neuropathic pain. REVIEW. Brain Res Brain Res Rev 51, 240-264 (2006).
• G17. Moalem-Taylor G, Allbutt HN, Iordanova MD & Tracey DJ. Pain hypersensitivity in rats with experimental autoimmune neuritis, an animal model of human inflammatory demyelinating neuropathy. Brain Behav Immun 21: 699-710 (2007).
• G18. Moalem-Taylor G, Lang PM, Tracey DJ & Grafe P. Post-spike excitability indicates changes in membrane potential of isolated C-fibers. Muscle Nerve 36:172-182 (2007).
• G19. Evans S, Moalem-Taylor G & Tracey DJ. Pain and endometriosis. REVIEW. Pain 132 Suppl 1: S22-5 (2007).
• G20. Li M, Peake P, Charlesworth J, Tracey DJ & Moalem-Taylor G. Complement activation contributes to leukocyte recruitment and neuropathic pain following peripheral nerve injury in rats. Eur J Neurosci 26: 3486–3500 (2007).
• G21. Smith F, Haskelberg H, Tracey DJ & Moalem-Taylor G. Role of Histamine H(3) and H(4) Receptors in Mechanical Hyperalgesia following Peripheral Nerve Injury. Neuroimmunomodulation 14: 317-325 (2007) Epub 2008 Apr 10.