Pain from tissue injury is usually brief and resolves as the injury heals. But some patients have chronic pain with no disease or recent injury in the painful area to explain it. These """"""""mystery pain"""""""" patients are poorly served by our health care system. Many among them have unappreciated nerve diseases or injuries that could be recognized and treated if we had better tests. The candidate is an MD, PhD neurologist and neuroscientist with research and clinical fellowship training in peripheral nerve as well as pain. Her long-term career goals are to identify and investigate neuropathic pain (neuralgia) syndromes, and to develop better objective methods for diagnosing and studying them. Neuralgia, whether caused by focal nerve injuries or diseases such as diabetes, is specifically associated with distal degeneration of the small diameter axons (small-fibers) that transmit pain sensations and regulate the body's tissue functions. Small-fiber damage is nearly impossible to diagnose by routine examination or testing (electromyography/nerve conduction studies), so many chronic pain patients remain in limbo without a diagnosis or effective treatment. The candidate's immediate career goal is to finish work showing that patients with focal neuralgia caused by injury have axonal degeneration in """"""""mirror"""""""" nerves on the opposite side of the body, as well as in nerves that were directly injured. The research career development plan includes establishing new multidisciplinary collaborations to develop new methods of studying and diagnosing small-fiber disease. The environment, Massachusetts General Hospital (MGH) at Harvard Medical School, provides outstanding resources, collaborators, and many potential clinician/investigator trainees from among the residents and fellows. The many chronic-pain patients seeking care at MGH, including those referred to the candidate's JCAHO-accredited skin biopsy laboratory for diagnosis of suspected small-fiber polyneuropathies, provide another resource for this project. At MGH such patients have a small distal-leg skin biopsy removed and immunolabeled to permit counting the small-fiber nerve endings within.
In Aim 1 patients scheduled for such skin biopsy testing will also be offered distal-leg, laser-Doppler, skin-blood-flow studies to evaluate if (and which) blood-flow measurements might provide a noninvasive substitute for skin-biopsy tests.
In Aim 2 these same patients will be offered ultrasound tests of heel-bone density to test the hypothesis that small-fiber polyneuropathies also cause bone loss. If this is true, such patients may have currently unappreciated risk for osteoporosis and bone fracture. Plus, modulating small-fiber effects on bone might offer potential new treatments for osteoporosis.
Aim 3 involves collaboration with MGH's neuroradiologists to optimize 3-Tesla magnetic resonance imaging equipment and methods to permit physicians to see the chronic nerve injuries that leave some patients with """"""""mystery pain"""""""" after seemingly minor or healed injuries.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
Application #
Study Section
NST-2 Subcommittee (NST)
Program Officer
Chen, Daofen
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts General Hospital
United States
Zip Code
Lang, Magdalena; Treister, Roi; Oaklander, Anne Louise (2016) Diagnostic value of blood tests for occult causes of initially idiopathic small-fiber polyneuropathy. J Neurol :
Oaklander, Anne Louise (2016) Immunotherapy Prospects for Painful Small-fiber Sensory Neuropathies and Ganglionopathies. Neurotherapeutics 13:108-17
Murphy, K; Oaklander, A L; Elias, G et al. (2016) Treatment of 213 Patients with Symptomatic Tarlov Cysts by CT-Guided Percutaneous Injection of Fibrin Sealant. AJNR Am J Neuroradiol 37:373-9
Oaklander, Anne Louise; Horowitz, Steven H (2015) The complex regional pain syndrome. Handb Clin Neurol 131:481-503
Treister, Roi; Nielsen, Christopher S; Stubhaug, Audun et al. (2015) Experimental comparison of parametric versus nonparametric analyses of data from the cold pressor test. J Pain 16:537-48
Scripko, Patricia; Oaklander, Anne Louise; Koeppen, Arnulf H et al. (2015) A 40-year-old woman with difficulty going down stairs in high-heeled shoes. Ann Neurol 77:1-7
Treister, R; O'Neil, K; Downs, H M et al. (2015) Validation of the composite autonomic symptom scale 31 (COMPASS-31) in patients with and without small fiber polyneuropathy. Eur J Neurol 22:1124-30
Klein, Max M; Treister, Roi; Raij, Tommi et al. (2015) Transcranial magnetic stimulation of the brain: guidelines for pain treatment research. Pain 156:1601-14
Fridman, Vera; Oaklander, Anne Louise; David, William S et al. (2015) Natural history and biomarkers in hereditary sensory neuropathy type 1. Muscle Nerve 51:489-95
Zhao, Wei; Cohen-Adad, Julien; Polimeni, Jonathan R et al. (2014) Nineteen-channel receive array and four-channel transmit array coil for cervical spinal cord imaging at 7T. Magn Reson Med 72:291-300

Showing the most recent 10 out of 28 publications