Sandra M. Garraway

Sandra M. Garraway is a Canadian-American neuroscientist and assistant professor of physiology in the Department of Physiology at Emory University School of Medicine in Atlanta, Georgia. Garraway is the director of the Emory Multiplex Immunoassay Core (EMIC) where she assists researchers from both academia and industry to perform, analyze, and interpret their multiplexed immunoassays. Garraway studies the neural mechanisms of spinal nociceptive pain after spinal cord injury and as a postdoctoral researcher she discovered roles for both BDNF and ERK2 in pain sensitization and developed novel siRNA technology to inhibit ERK2 as a treatment for pain.

Early life and education Garraway pursued her Bachelors of Arts at the University of Guelph, in Guelph, Ontario, Canada. She graduated in 1993 and moved to Mantioba where she pursued her graduate studies at the University of Manitoba, in Winnipeg, Manitoba, Canada. She studied under the mentorship of Shawn Hochman in the Department of Physiology exploring synaptic plasticity in deep dorsal horn (DDH) neurons since they play a fundamental role in nociception and relaying pain information to the brain. Garraway published four first-author papers during her PhD.

Mechanisms of plasticity in deep dorsal horn neurons Garraway explored how primary afferent stimulation impacted plasticity, in the form of long term potentiation (LTP) or long term depression (LTD), of the DDH neurons. LTP and LTD had only just been identified in the spinal cord, and Garraway discovered that LTP and LTD can also be induced in the DDH neurons with even lower frequency afferent stimulation. She used an in vitro slice preparation of DDH neurons and applied various serotonin receptor ligands to assess the effects of modulation at each serotonin receptor subtype in the primary afferent neurons. Further, Garraway found that the addition of both serotonin and norepinephrine simultaneously could evoke even greater depression than either in isolation. Studying under Lorne Mendell, she explored the implications of brain-derived neurotrophic factor (BDNF) on central sensitization and exaggerated pain states. Garraway found that BDNF signalling in the dorsal horn led to facilitation, and the initiation of this facilitation was dependent on NMDA receptor signalling and phospholipase C. She found that after neonatal spinal injury, BDNF was no longer able to facilitate dorsal-root EPSCs. This led to decreased mechanical allodynia after injection of an inflammatory agent. Both of her results show that vector-derived siRNAs targeting the NR1 subunit of the AMPA receptor might be beneficial in the treatment of pain by reducing expression of genes mediating pain sensation in the spinal cord. In 2014, Garraway was recruited to Emory University where she was appointed to Assistant Professor of Physiology at the School of Medicine. Garraway is also a Faculty Member for the Neuroscience Graduate Program at Emory. The Garraway Lab is funded by the Craig Neilsen Foundation, the National Institutes of Health, and the Department of Defense.

Garraway is also a member of various national and international groups working to study pain and find cures and treatments for pain disorders. Garraway is a member of the International Pain Research Forum and is also a member of The Institute for Rehabilitation and Research (TIRR) Foundation a collaborative research foundation that innovates therapies for people with sustained nervous system damage.

Role of BDNF in pain sensitization After discovering a role for spinal cord BDNF signaling in pain sensitization in her postdoc, Garraway explored whether the behavioral correlates of pain were associated with cellular changes mediated by BDNF. She found that nociceptive stimulation decreased expression of BDNF, TrkB, and ERK2 in the dorsal spinal cord. After instrumental training, where rats learned to not flex their hind limb to prevent pain, there were increases in BDNF and increased plasticity. Further, when BDNF was injected during uncontrollable pain stimulation, it blocked allodynia and enabled rats to learn to not extend their hind legs. In 2015, she discovered increases in TNFa expression after nociceptive stimulation post spinal cord injury and that downstream TNFa signalling may induce apoptosis in neurons and microglia.

Awards and honors

2015 Department of Defense Congressional Directed Medical Research Programs Award Martin KK, Parvin S, Garraway SM. Peripheral Inflammation Accelerates the Onset of Mechanical Hypersensitivity after Spinal Cord Injury and Engages Tumor Necrosis Factor α Signaling Mechanisms. J Neurotrauma. 2019;36(12):2000‐2010. doi:10.1089/neu.2018.5953 Garraway SM, Woller SA, Huie JR, et al. Peripheral noxious stimulation reduces withdrawal threshold to mechanical stimuli after spinal cord injury: role of tumor necrosis factor alpha and apoptosis. Pain. 2014;155(11):2344‐2359. doi:10.1016/j.pain.2014.08.034 Garraway SM, Turtle JD, Huie JR, et al. Intermittent noxious stimulation following spinal cord contusion injury impairs locomotor recovery and reduces spinal brain-derived neurotrophic factor-tropomyosin-receptor kinase signaling in adult rats. Neuroscience. 2011;199:86‐102. doi:10.1016/j.neuroscience.2011.10.007 Garraway SM, Xu Q, Inturrisi CE. siRNA-mediated knockdown of the NR1 subunit gene of the NMDA receptor attenuates formalin-induced pain behaviors in adult rats. J Pain. 2009;10(4):380‐390. doi:10.1016/j.jpain.2008.09.013 Garraway SM, Xu Q, Inturrisi CE. Design and evaluation of small interfering RNAs that target expression of the N-methyl-D-aspartate receptor NR1 subunit gene in the spinal cord dorsal horn. J Pharmacol Exp Ther. 2007;322(3):982‐988. doi:10.1124/jpet.107.123125 Garraway SM, Petruska JC, Mendell LM. BDNF sensitizes the response of lamina II neurons to high threshold primary afferent inputs. Eur J Neurosci. 2003;18(9):2467‐2476. doi:10.1046/j.1460-9568.2003.02982.x Garraway SM, Hochman S. Modulatory actions of serotonin, norepinephrine, dopamine, and acetylcholine in spinal cord deep dorsal horn neurons. J Neurophysiol. 2001;86(5):2183‐2194. doi:10.1152/jn.2001.86.5.2183 Garraway SM, Hochman S. Pharmacological characterization of serotonin receptor subtypes modulating primary afferent input to deep dorsal horn neurons in the neonatal rat. Br J Pharmacol. 2001;132(8):1789‐1798. doi:10.1038/sj.bjp.0703983 Garraway SM, Pockett S, Hochman S. Primary afferent-evoked synaptic plasticity in deep dorsal horn neurons from neonatal rat spinal cord in vitro. Neurosci Lett. 1997;230(1):61‐64. doi:10.1016/s0304-3940(97)00475-8