Regardless of the scale of peripheral nerve damage, human neonates usually suffer no chronic neuropathic pain. However, by early adulthood, this situation is starkly different, with rates of chronic pain related to the severity of nerve injury, genetic makeup and as yet undetermined risk factors. Rodents display similar age related traits in differential neuropathic hypersensitivity and we have used this phenomenon to perform a whole genome expression screen of the spinal dorsal horns ipsilateral to the injured sciatic nerve from neonates (with no hypersensitivity) and adults (with chronic pain-like symptoms). We found virtually all of the genes regulated in the adult, but not in the neonate were immune related, and within this group we found evidence for the presence of two cell types, microglia and T lymphocytes. As we had previously characterized the role of microglia, we further defined the role of T cells in this process. Preventing T cell function in adult animals resulted in marke decreases in pain-like behavior, suggesting that T cell migration into the nervous system was a crucial part of chronic neuropathic pain, a mechanism that has remained largely unrecognized to date. Here we wish to define this system further, by (1) blocking leukocyte action and infiltration in adult animals subject to peripheral nerve injury;(2) investigating the mechanisms f T cell recruitment to the sciatic nerve injury site (neuroma), the dorsal root ganglion, and the dorsal horn following nerve injury;(3) separating and defining the individual roles of the T helpe cell subtypes (Th1, Th2, Th17 and T regulatory) by gain and loss of function techniques.

Public Health Relevance

Neuropathic pain is a chronic disease with few effective therapies that destroys the lives of those that suffer its devastating consequences. Its treatment thus represents a major unmet clinical need. We have found that immune cells from the blood (T cells) infiltrate the peripheral nervous system and spinal cord following injury to peripheral sensory nerves and contribute to this pain. We believe we have found an important new mechanism of neuropathic pain, one with existing therapies designed for other conditions that may prove beneficial in reducing chronic pain symptoms.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
Project #
Application #
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Babcock, Debra J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Children's Hospital Boston
United States
Zip Code
Banno, Tomohiro; Omura, Takao; Masaki, Noritaka et al. (2017) Arachidonic acid containing phosphatidylcholine increases due to microglial activation in ipsilateral spinal dorsal horn following spared sciatic nerve injury. PLoS One 12:e0177595
Tedeschi, Andrea; Omura, Takao; Costigan, Michael (2017) CNS repair and axon regeneration: Using genetic variation to determine mechanisms. Exp Neurol 287:409-422
Chandran, Vijayendran; Coppola, Giovanni; Nawabi, Homaira et al. (2016) A Systems-Level Analysis of the Peripheral Nerve Intrinsic Axonal Growth Program. Neuron 89:956-70
Latremoliere, Alban; Latini, Alexandra; Andrews, Nick et al. (2015) Reduction of Neuropathic and Inflammatory Pain through Inhibition of the Tetrahydrobiopterin Pathway. Neuron 86:1393-406
Dulin, Jennifer N; Antunes-Martins, Ana; Chandran, Vijayendran et al. (2015) Transcriptomic Approaches to Neural Repair. J Neurosci 35:13860-7
Omura, Takao; Omura, Kumiko; Tedeschi, Andrea et al. (2015) Robust Axonal Regeneration Occurs in the Injured CAST/Ei Mouse CNS. Neuron 86:1215-27
Vicuña, Lucas; Strochlic, David E; Latremoliere, Alban et al. (2015) The serine protease inhibitor SerpinA3N attenuates neuropathic pain by inhibiting T cell-derived leukocyte elastase. Nat Med 21:518-23
Yang, Fei; Fu, Han; Lu, Yun-Fei et al. (2014) Post-stroke pain hypersensitivity induced by experimental thalamic hemorrhage in rats is region-specific and demonstrates limited efficacy of gabapentin. Neurosci Bull 30:887-902
Young, Erin E; Costigan, Michael; Herbert, Teri A et al. (2014) Heritability of nociception IV: neuropathic pain assays are genetically distinct across methods of peripheral nerve injury. Pain 155:868-80
Xie, Fang; Fu, Han; Hou, Jun-Feng et al. (2013) High energy diets-induced metabolic and prediabetic painful polyneuropathy in rats. PLoS One 8:e57427

Showing the most recent 10 out of 14 publications