Many chronic pain patients complain of abnormal sensitivity to multiple sensory modalities, including light, sound, and smell. The underlying neural basis remains a puzzle and these claims are often viewed with suspicion, since sensory acuity per se is not enhanced, nor is there amplified processing in primary sensory pathways. The central thesis of this proposal is that dysfunction of brainstem pain-modulating systems, already thought to contribute to pain in these conditions, is also likely to play a role in multisensory hypersensitivity. This hypothesis is based on our unexpected observation that a subset of pain-modulating neurons in the rostral ventromedial medulla, the final output of an important brainstem pain-modulating system, respond to light. In three Specific Aims using single-cell recording approaches in rat, we will fully characterize the RVM response to light, generating stimulus-response functions and establishing the relevant spectrum. We will also determine whether photoresponsiveness of these neurons is enhanced in an animal model of migraine headache (where photosensitivity is well documented) or in a persistent inflammatory state. Finally, we will investigate ?top-down? modulation of photoresponsiveness from a higher brain structure known to contribute to stress-induced hyperalgesia and implicated in endocrine, autonomic, and behavioral responses to mild stress. The present proposal brings together electrophysiological and behavioral approaches to determine how light engages pain-modulating systems, effectively converting a visual stimulus to a somatic sensation, producing discomfort and aversion. These studies will provide fundamental insights into the neurobiological mechanisms of multisensory hypersensitivity, information critical to developing more appropriate treatments for migraine and other chronic pain disorders.

Public Health Relevance

We now understand that the brain actively controls our sensitivity to pain. An imbalance in the brain's modulatory systems so that pain transmission is favored can contribute to chronic pain and make it difficult to treat. The work proposed in this application will study how different forms of sensory information gain access to pain-modulating systems, influencing the balance between greater or lesser pain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37NS098660-02
Application #
9413274
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Oshinsky, Michael L
Project Start
2017-01-15
Project End
2020-11-30
Budget Start
2017-12-01
Budget End
2018-11-30
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239