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Exposing the skin to high levels of ultraviolet B (UVB) radiation induces an inflammatory response that upregulates local nociceptive processing; this, in turn, facilitates protective responses to limit further injury. In this study, the UVB model was used to explore additional effects of inflammation on supraspinal nociceptive processing. Thirty-one healthy participants attended two sessions approximately 24 h apart. In each session, pressure-pain thresholds and sensitivity to sharp stimulation and heat were assessed in both forearms, and pressure-pain thresholds and sensitivity to sharp stimulation were assessed on each side of the forehead. In a novel paradigm, supraspinal nociceptive processing was explored by assessing pain and blink reflexes to electrical stimulation of the forehead, paired with acoustic startle stimuli. At the end of the first session, UVB radiation at a dose sufficient to induce erythema at the most exposed site was administered to one forearm. Consistent with local sensitization, sensitivity to heat and sharp stimulation had increased at the maximally exposed site 24 h later. This local response was accompanied by changes in supraspinal nociceptive processing-pressure-pain thresholds were lower on the ipsilateral than contralateral side of the forehead, and acoustic startle stimuli augmented electrically evoked pain. Blink reflexes weakened from the first to the second session, but decreases were smaller on the UVB-treated than contralateral side. Together, these findings suggest that acoustic startle stimuli facilitated activity in sensitized supraspinal nociceptive pathways. Potentially, this supraspinal mechanism adds to the burden of chronic nociplastic pain during states of heightened arousal and stress.
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http://dx.doi.org/10.1155/prm/6601529 | DOI Listing |
Neuropharmacology
August 2025
Ningbo Municipal Hospital of Traditional Chinese Medicine, Affiliated Hospital of Zhejiang Chinese Medical University, Ningbo, 315010, China. Electronic address:
Lumbar disc herniation (LDH) is a major driver of chronic low back pain often accompanied by depression-like behaviors, yet the supraspinal mechanisms that link nociception to affective disturbance remain unclear. Here, we investigated the potential mechanisms by which microglia-derived nitric oxide (NO) modulates synaptic plasticity in the amygdala of a rat model of LDH. Behavioral assessments confirmed the presence of mechanical hyperalgesia and depression-like behaviors in LDH rats.
View Article and Find Full Text PDFNeurochem Res
August 2025
Neuroscience Institute, National Research Council (CNR), Padova, Italy.
Chronic pain is a debilitating, life-altering condition that affects a significant portion of the global population, impacting approximately one fifth of people in Europe and one third of people worldwide. Clinical and experimental efforts are increasingly converging to deepen our comprehension of the molecular, cellular and circuit-level mechanisms underlying persistent pain. While most studies have traditionally focused on alterations of nociceptive pathways in neurons, growing evidence highlights the critical role of astrocytes in modulating these pathways and contributing to the development of the central sensitization that characterizes chronic pain.
View Article and Find Full Text PDFPain
August 2025
Department of Pharmacology and Physiology and the Institute for Translational Neuroscience, Saint Louis University School of Medicine, St. Louis, MO, USA.
Activation of sphingosine-1-phosphate (S1P) receptor 1 (S1PR1) in the spinal cord contributes to neuropathic pain; however, its role at supraspinal sites remains unexplored. Ozanimod is a new FDA-approved S1PR1 antagonist for multiple sclerosis. Here, we show that systemic ozanimod administration reverses behavioral hypersensitivities in male rodents induced by chronic sciatic nerve constriction and chemotherapy (oxaliplatin and paclitaxel).
View Article and Find Full Text PDFPain Res Manag
July 2025
School of Psychology and Centre for Healthy Ageing, College of Health and Education, Murdoch University, 90 South Street, Murdoch, Western Australia 6150, Australia.
Exposing the skin to high levels of ultraviolet B (UVB) radiation induces an inflammatory response that upregulates local nociceptive processing; this, in turn, facilitates protective responses to limit further injury. In this study, the UVB model was used to explore additional effects of inflammation on supraspinal nociceptive processing. Thirty-one healthy participants attended two sessions approximately 24 h apart.
View Article and Find Full Text PDFJ Physiol Sci
July 2025
Department of Anatomy, Université du Québec à Trois-Rivières, Trois-Rivières, QC G9A 5H7, Canada. Electronic address:
The aim of the present study was to examine the contribution of spinal and supraspinal processes to pain modulation by attention. It is hypothesized that pain inhibition by distraction is accompanied by reduced pain-evoked pupil dilation and cerebral activity, but no inhibition of the nociceptive flexion reflex (NFR), while pain anticipation is expected to increase pain perception and pain-related responses. Twenty healthy volunteers received 90 painful stimuli in control, distraction (mental arithmetic), and anticipation (visual cue) conditions.
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