# In-vivo imaging of spinal and brain glial activation in low back pain patients

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $704,282

## Abstract

In animal models of pain, microglia and astrocytes become `activated' and start releasing pro-
inflammatory cytokines and other products that further sensitize pain pathways. Thus, it is generally believed
that glial cells actively contribute to the pathophysiology of persistent pain. Despite hundreds of studies with
laboratory models, it is currently unclear whether glial cells have a role in human pain. Recently, however, our
group has demonstrated that patients with chronic low back pain (cLBP) have increased brain levels of the
18kDa translocator protein (TSPO). In addition, preliminary data collected from a different cohort of cLBP
patients suggest an increase in spinal cord TSPO levels as well. As TSPO upregulation is a marker of glial
activation, these observations support a role for glial activation in human chronic pain.
 With the current proposal, which builds logically on our prior observations, we will compare spinal and
brain glial activation in healthy volunteers, and patients with subacute (i.e., pain duration between 1 and 3
months) and chronic (i.e., pain duration > 1 year) low back pain. Scans will be performed with integrated
Positron Emission Tomography / Magnetic Resonance (PET/MR) imaging and [11C]PBR28, a second-
generation radioligand for TSPO, with an excellent ratio of specific-to-nonspecific binding. By comparing
[11C]PBR28 scans in cLBP patients of different clinical presentation (i.e., with radicular pain vs axial pain) we
will test the hypothesis that glial activation in the primary somatosensory/motor cortices follows a somatotopic
organization that mirrors the somatic distribution of the patients' symptoms. Moreover, we will perform cross-
sectional comparisons between subacute and chronic low back pain, as well as longitudinal studies of
subacute low back pain patients across time, to capture the transition to chronic pain, or the return to pain-free
status. These investigations will allow us to assess the temporal evolution of glial activation in humans with
pain disorders. A subset of sLBP patients will be re-scanned after a 2-week treatment with either minocycline
(which was recently found to reduce sLBP) or placebo. While minocycline is a known glial inhibitor in animal
models, the mechanisms underlying its effect on human pain are unknown. Finally, we will compare the
baseline status of glial activation in subacute patients that have subsequently transitioned to chronic pain, or
have healed. This comparison will allow us to test the hypothesis that glial activation can predict transition from
subacute to chronic pain.
 While this project is purposely focused on a specific condition (low back pain), the identification of a role
of glia in the development and maintenance of persistent pain and pain-related disability will have important
practical implications for the management of a wide range of pain disorders.

## Key facts

- **NIH application ID:** 9973239
- **Project number:** 5R01NS095937-05
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Marco Luciano Loggia
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $704,282
- **Award type:** 5
- **Project period:** 2016-09-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9973239

## Citation

> US National Institutes of Health, RePORTER application 9973239, In-vivo imaging of spinal and brain glial activation in low back pain patients (5R01NS095937-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9973239. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*