Brazilian journal of physical therapy · 2025
Blockade of opioid receptors prevents the effect of exercise on neuropathic pain in mice, promoting immunoregulation in the brainstem and prefrontal cortex.
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Belle Fernanda, Lins Elisa Mitkus Flores, Mack Josiel Mileno, da Silva Francielly Suzaine, Gelain Ludmilla Solange, Horewicz Verônica Vargas, Traebert Guilherme de Azevedo, Buffon Alexandre Carlos, Hizume-Kunzler Deborah de Camargo, Martins Daniel Fernandes, Bobinski Franciane
Аннотация
BACKGROUND: Physical exercise is widely recognized for reducing neuropathic pain. However, the interaction between the immune and opioidergic systems in supraspinal structures is still not fully understood.
OBJECTIVE: To evaluate the impact of opioid receptor blockade on the effects of low-intensity exercise on the sensory, cognitive, and emotional aspects of neuropathic pain after sciatic nerve injury.
METHODS: Male Swiss mice (2 months old) were submitted to sciatic nerve crush and divided into sedentary or exercised groups. The exercised groups performed treadmill running for two weeks, with or without naloxone pre-treatment to block opioid receptors. Sensory responses were assessed using the von Frey test, while cognitive and emotional-like behaviors were evaluated through the Mechanical Conflict-Avoidance System (MCAS) and open field test, respectively. Cytokine levels (IL-4, IL-10) and brain-derived neurotrophic factor (BDNF) were quantified in the brainstem and prefrontal cortex by ELISA.
RESULTS: Exercise reduced mechanical hypersensitivity and improved performance in cognitive and exploratory tasks. These effects were prevented by naloxone administration. Exercise also increased IL-4, IL-10, and BDNF levels in supraspinal regions, while naloxone reversed these changes, indicating the involvement of μ-opioid receptors in exercise-induced immunomodulation.
CONCLUSION: Low-intensity exercise promotes analgesia and neuroimmune regulation in neuropathic pain through supraspinal μ-opioid receptor activation. The blockade of these receptors abolishes the beneficial effects of exercise, reinforcing the interaction between opioidergic and immune systems in pain modulation.
OBJECTIVE: To evaluate the impact of opioid receptor blockade on the effects of low-intensity exercise on the sensory, cognitive, and emotional aspects of neuropathic pain after sciatic nerve injury.
METHODS: Male Swiss mice (2 months old) were submitted to sciatic nerve crush and divided into sedentary or exercised groups. The exercised groups performed treadmill running for two weeks, with or without naloxone pre-treatment to block opioid receptors. Sensory responses were assessed using the von Frey test, while cognitive and emotional-like behaviors were evaluated through the Mechanical Conflict-Avoidance System (MCAS) and open field test, respectively. Cytokine levels (IL-4, IL-10) and brain-derived neurotrophic factor (BDNF) were quantified in the brainstem and prefrontal cortex by ELISA.
RESULTS: Exercise reduced mechanical hypersensitivity and improved performance in cognitive and exploratory tasks. These effects were prevented by naloxone administration. Exercise also increased IL-4, IL-10, and BDNF levels in supraspinal regions, while naloxone reversed these changes, indicating the involvement of μ-opioid receptors in exercise-induced immunomodulation.
CONCLUSION: Low-intensity exercise promotes analgesia and neuroimmune regulation in neuropathic pain through supraspinal μ-opioid receptor activation. The blockade of these receptors abolishes the beneficial effects of exercise, reinforcing the interaction between opioidergic and immune systems in pain modulation.