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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24NS059892-05
Application #
8252176
Study Section
NST-2 Subcommittee (NST)
Program Officer
Chen, Daofen
Project Start
2008-04-01
Project End
2013-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
5
Fiscal Year
2012
Total Cost
$190,031
Indirect Cost
$14,076
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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AbdelRazek, Mahmoud A; Chwalisz, Bart; Oaklander, Anne Louise et al. (2017) Evidence of small-fiber neuropathy (SFN) in two patients with unexplained genital sensory loss and sensory urinary cystopathy. J Neurol Sci 380:82-84
Treister, Roi; Lodahl, Mette; Lang, Magdalena et al. (2017) Initial Development and Validation of a Patient-Reported Symptom Survey for Small-Fiber Polyneuropathy. J Pain 18:556-563
Oaklander, Anne Louise (2016) Immunotherapy Prospects for Painful Small-fiber Sensory Neuropathies and Ganglionopathies. Neurotherapeutics 13:108-17
Oaklander, Anne Louise (2016) What is the meaning of ""small-fiber polyneuropathy"" in fibromyalgia? An alternate answer. Pain 157:1366-7
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
Lang, Magdalena; Treister, Roi; Oaklander, Anne Louise (2016) Diagnostic value of blood tests for occult causes of initially idiopathic small-fiber polyneuropathy. J Neurol 263:2515-2527
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
Oaklander, Anne Louise; Horowitz, Steven H (2015) The complex regional pain syndrome. Handb Clin Neurol 131:481-503

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