161: Brain mechanisms supporting movement-evoked pain flares in patients with chronic low back pain

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Chronic neuropathic pain, Pain in Special Populations , Imaging (e.g. fMRI, PET, MRS)

Background and Aims: Chronic low back pain (cLBP) is the leading cause of disability globally[1] and commonly exacerbated by movements such as bending over or lifting objects[2-3]. The transition from acutely evoked to stabilized neuroplastic chronic pain is associated with higher self-referential, sensory and nociceptive processing. However, neural mechanisms supporting movement-evoked pain in cLBP remain poorly characterized. The leg raise test (LRT), an ecologically validated cLBP evoking technique[4-5], increases activity in pain-related areas including primary (SI) and secondary somatosensory cortices (SII), insula[6-7], superior parietal lobule[5], and self-referential processing in regions of the default mode network (DMN)[8-11]. This study examined behavioral and neural responses to the LRT using arterial spin labeling (ASL) functional MRI[12-13] in patients diagnosed with lumbar radiculopathy. We hypothesized that the LRT would significantly increase self-reported pain and cerebral blood flow (CBF) in brain regions supporting nociceptive (SI, insula), sensory discriminative (parietal lobe) and self-referential (precuneus, medial prefrontal cortex) processing.

Methods: Perfusion-based ASL functional MRI was performed in 114 patients with cLBP (58 male; mean age 46 ± 12 years) while lying supine and following the cLBP-evoking LRT. Patients rated the intensity and unpleasantness of their cLBP before and after each LRT with an 11-point visual analog scale (0= no pain, 10= most intense/unpleasant pain imaginable). Patients also completed the Brief Pain Inventory (BPI)[14-15] to assess chronic pain severity and interference. Paired samples t-tests assessed for changes in pain before and after LRT exacerbation of cLBP (R v4.4.1). Whole-brain CBF changes from supine to LRT were quantified. Post-LRT pain intensity ratings were regressed on the aforementioned LRT-evoked CBF change to identify neural correlates of movement-evoked pain ratings (FSL FEAT; cluster corrected Z>3.1, p<.05). Blood oxygen-level dependent (BOLD) fMRI was also used to identify DMN-whole brain resting state functional connectivity supporting BPI-based chronic pain (FSL FEAT; Z>3.1, p<.05).

Results: The LRT significantly (ps<.001) increased pain intensity by 23% (t(226)=8.75) and pain unpleasantness by 26% (t(226)=8.45) compared to pre-LRT pain. Compared with supine, the LRT significantly increased CBF in core DMN nodes including the medial prefrontal and posterior cingulate cortices. In addition, LRT significantly increased nociceptive processing in the thalamus, parietal operculum, supplementary motor area, and the primary motor cortical representation of the back. Importantly, higher LRT-evoked pain intensity (but not unpleasantness) ratings were significantly associated with greater CBF in the left superior parietal lobule, supramarginal gyrus, and bilateral SI and primary motor cortices. Post-LRT pain intensity ratings were significantly (ps<.001) associated with higher chronic pain severity (b=0.40) and interference (b=0.38). Greater chronic pain severity, but not interference, was associated with stronger resting state functional connectivity between the DMN and bilateral SI representations of the back, left SII, superior parietal lobule, precuneus, and visual cortex.

Conclusions: The present study provides novel evidence for the integrative role of self-referential and sensory-processing in acutely-evoked and stabilized cLBP. Movement-evoked cLBP was associated with greater self-referential and nociceptive processing. LRT-evoked activation of the DMN contrasts with healthy individuals which exhibit DMN deactivation during evoked pain[6,16-18]. DMN activation, observed here, may indicate a shift toward egocentric pain evaluation coupled with heightened sensory awareness of back-provocative stimuli, as evidenced by greater SI responses to LRT-evoked pain and greater DMN-SI functional connectivity associated with higher pain severity. These mechanisms may contribute to the limited efficacy of pharmacologic analgesia for activity-related pain and highlight the importance of incorporating movement-evoked paradigms when evaluating intervention efficacy. Although speculative, the present results suggest that interventions such as meditation or psychedelic therapy, which target the self-referential and nociceptive neural mechanisms observed here, may be uniquely effective at reducing movement-evoked cLBP.

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Presenting Author: Morgan Gianola
Submitting Author: Morgan Gianola

Senior Author: Fadel Zeidan

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Jon Dean: PhD - University of California San Diego
• Conan Chen: BA - University of California San Diego
• Daniel Barrows: MS - University of California San Diego
• Gabriel Riegner: BS - University of California San Diego
• Thomas Liu: PhD - University of California San Diego
• Fadel Zeidan: PhD - University of California San Diego