PROJECT SUMMARY
Significance: Chronic pain affects 30% of the adult population in the USA and presents with multiple co-morbid
psychiatric disorders, including mood alterations and cognitive impairment. Despite the severity of this problem,
clinicians often rely on a “trial and error” approach to find a strategy that provides some measure of relief. This
is mainly because most pain treatments were implemented based on clinical observations rather than a mechanistic
understanding of chronic pain. One of the pivotal mechanisms that could explain the chronification of pain as
well as its resistance to classical treatment is the concept of pain centralization, where initial sensory events
following trauma can gradually alter the central nervous system (CNS), resulting in amplified pain and/or aberrant
pain that exists without peripheral sensitization. However, most of the research in this area focuses on cellular
mechanisms and overlooks the extracellular matrix (ECM) in which these cells function. The proposed research
aims to delineate the role of brain ECM components in pain-related cellular and structural plasticity, thereby
expanding our knowledge of the effects of chronic pain on the brain.
Innovation: The proposed study is multimodal in nature and incorporates techniques related to animal behavior,
cell physiology, biochemistry, cell culture, pharmacology, and microscopy. For instance, ECM rigidity will be
assessed by using structural (microarchitectural analysis following scanning electron microscopy and physical
rigidity using atomic force microscopy) as well as biochemical analyses (immunohistochemistry and protein
quantification). Similarly, the role of specific ECM components will be evaluated both in vivo (pharmacology)
and in vitro (using a unique decellularized brain substrate for neuronal culture). Upon the completion of the
proposed studies, the developed toolset can be a useful asset in studying brain areas outside the hippocampus.
Participation of underrepresented minorities in the biomedical/behavioral sciences: Consistent with the
NIH’s mission of training and graduating students from groups nationally underrepresented in biomedical
research, the current proposal specifically targets the diverse student body of Queens College, CUNY. Queens
College boasts high levels of ethnic and socioeconomic diversity and Dr. Tajerian is committed to mentoring the
many undergraduate and graduate students in her department. She has extensive mentorship experience both at
McGill at Stanford universities, and her current laboratory members include students from diverse backgrounds.
Dr. Tajerian is also part of the MARC-U*STAR mentoring program. Maximizing Access to Research Careers is
an Undergraduate Student Training program in Academic Research. It is the first NIH program specifically
focused on directing under-represented minority students toward graduate school and biomedical research careers.
Timeline and developmental objectives: The proposed timeline for the outlined experiments is 3 years. Data
collected for the duration of this grant, in addition to the acquired technical expertise, will be instrumental in the
acquisition of R01 level funding in the field of brain extracellular matrix alterations in chronic pain.