Frontal Biochemical Metabolites in Aging and Chronic Pain

Jessica Reade

Authors:  Yenisel Cruz-Almeida, MSPH, PhD, Eric Porges, PhD, Adam Woods, PhD, Jessica Reade, BHS, Lorraine Hoyos, BS, Corey Nack, BS, Ronald Cohen, PhD 

Faculty Mentor:  Yenisel Cruz-Almeida, MSPH, PhD 

College:  College of Medicine


Neurochemical brain alterations have been reported in aging and in persons with chronic pain. Given chronic pain is highly prevalent in older individuals, it is not currently known whether neurochemical brain alterations are associated with older age and/or chronic pain. The goal of the study was to determine age and pain differences in brain neurochemistry. NEPAL study participants included younger (18-26 years,n=20) and cognitively intact older adults with (n=25, pain>3 months) and without chronic pain (n=13, age=71.7±7.8, 63% female). We acquired a frontal brain voxel (1H-MRS) using a MEGA-PRESS sequence to measure the following metabolite concentrations reflecting neuronal health (N–acetyl aspartate [NAA]), glial activation/neuroinflammation (Myo-Inositol [Ins]), cell membrane turnover (total choline [tCho]), and energy metabolism (total creatine [tCr]). Older individuals had significantly lower [NAA] compared to younger controls (p=0.0003), and alternatively significantly greater [Ins], [tCr] and [tCho] compared to younger controls (p=0.016, p=0.027 and p=0.016, respectively). Older adults with chronic pain had greater [Ins] compared to those without pain (p=0.027). No other metabolites differed significantly between the groups. Our findings suggest that aging is associated with metabolites reflecting neuronal health, cell membrane turnover, and energy metabolism while pain in older individuals accounted for differences in glial activation and neuroinflammation.

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10 Responses
  1. Sarah

    Hey Jessica, great presentation! For my senior thesis work I will also being working with brain metabolites like NAA and love learning more about these.
    What is meant by “membrane turnover”?


    1. Jessica Reade

      Hi Sarah,

      I’m so excited for you to enter this research! I wish you the best of luck going into your senior year.

      Regarding your question about cell membrane turnover, all cells have surface membranes. Membrane turnover is a mechanism that maintains the cell surface area. This is especially essential to normal function of the cell in cells with expanded surface areas, such as cells lining the airways of the lungs. I hope that answers your question!

  2. Angela Lindner

    Hello, Jessica! I am just sending my praises for your presentation. Thank you for representing UF and Gators so well.

    1. Jessica Reade

      Hello, Dr. Lindner!

      Thank you kindly for your warm words. It is always a pleasure to work with you and learn from you, Go Gators!

  3. Julia Johnston

    Hi Jessica! Very interesting work you did this year, and great job with your video! You mentioned additional research in the future, what would this entail?

    1. Jessica Reade

      Hi Julia,

      Thank you so much!

      Regarding your question, we see that a possible limitation of this study was the restricted cohort of participants, as the study was conducted at the University of Florida on individuals local to the Gainesville area. Future research is necessary to further inspect this relationship in a wider population that is more representative and encompassing of the older cohort along with individuals who experience chronic pain. By means of further observation of the relationship between neurochemical and metabolic changes and an aged central nervous system versus the experience of chronic pain, we hope to one day have a more thorough understanding of comorbidities such as chronic pain and whether they have a more prominent impact on the brain in older adults. I hope this answers your question!

  4. Corinne Evans

    I really enjoyed watching your presentation and exploring your poster! I’m unfamiliar with this area of research, but I found your results to be very interesting and you presented the topic in a way that was understandable. I was wondering what you view as the potential clinical implications for this line of research going forward?

    1. Jessica Reade

      Hi Corrine,

      Thank you so much!

      Regarding your question, Geriatrics is the field of medicine dealing with the health and care of older individuals, and this branch of medicine has been underserved for a long duration of time. I personally have a vested interest in the field of geriatrics after seeing first hand how underserved the geriatric population really is through volunteering with hospice and nursing homes. In many situations, the elderly population is not always treated with the respect, kindness, and quality of care that they deserve. When I first looked into the NEPAL study, I was very pleased with the research being conducted specifically looking into the elderly cohort and that was what drew me into this specific research. Even though chronic pain affects individuals of all races, ages and genders, members of certain population groups are disproportionately affected, particularly seen as being more prevalent and disabling in older adults. Aging has been shown to have a prominent impact on the brain in older adults. Specifically, changes to the brain’s cellular and molecular integrants, as well as its macroscopic structure, due to aging have been noted, and we know that brain alterations are potential contributors to increased pain in older individuals. This research conducted will hopefully be beneficial in making breakthroughs regarding better treatment options and prevention for chronic pain in the elderly population to improve their quality of life. I hope this answers your question!

  5. Abhaya Dilip

    Hi, Jessica!

    It was very interesting to learn about the differences in the presence of various metabolites between younger and older adults. Going forward with clinical applications of this research, do you think it is possible to develop some sort of drug that could potentially inhibit the increase in Myo-Inositol (Ins) concentrations to prevent or decrease chronic pain?

    -Abhaya Dilip

    1. Jessica Reade

      Hi Abhaya,

      I am happy to hear you found this research interesting! I think that clinical application is an amazing idea and would definitely be applicable! Our results showed that older adults with chronic pain had greater Myo-Inositol [Ins] compared to those without pain (p=0.027), while no other metabolites differed significantly. A wonderful next step would be to determine our ability to inhibit the increase in [Ins] possibly via medication and conduct clinical trials to see whether the increase in severity of chronic pain has been inhibited! GREAT idea!