Role of brainstem serotonin in analgesia produced by low-intensity exercise on neuropathic pain after sciatic nerve injury in mice
Autor: | Claudio Da Cunha, Marina Machado Córdova, Franciane Bobinski, Cristina Martins-Silva, Kathleen A. Sluka, Anicleto Poli, Rita Gomes Wanderley Pires, Adair R.S. Santos, Tamara Andrea Alarcon Ferreira, Caroline Cunha do Espírito Santo, Patrícia A. Dombrowski |
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Rok vydání: | 2015 |
Předmět: |
Serotonin
medicine.medical_specialty Tyrosine 3-Monooxygenase Interleukin-1beta Physical exercise Tryptophan Hydroxylase Article Mice Peripheral Nerve Injuries Physical Conditioning Animal Internal medicine medicine Fenclonine Animals Enzyme Inhibitors Serotonin Plasma Membrane Transport Proteins Behavior Animal Tumor Necrosis Factor-alpha business.industry Chronic pain Hydroxyindoleacetic Acid Tryptophan hydroxylase Sciatic nerve injury medicine.disease Sciatic Nerve alpha-Methyltyrosine Anesthesiology and Pain Medicine Endocrinology Neurology Receptors Serotonin Neuropathic pain Peripheral nerve injury Neuralgia Alpha-Methyltyrosine Neurology (clinical) business Brain Stem medicine.drug |
Zdroj: | Pain. 156:2595-2606 |
ISSN: | 0304-3959 |
Popis: | Physical exercise is a low-cost, safe, and efficient intervention for the reduction of neuropathic chronic pain in humans. However, the underlying mechanisms for how exercise reduces neuropathic pain are not yet well understood. Central monoaminergic systems play a critical role in endogenous analgesia leading us to hypothesize that the analgesic effect of low-intensity exercise occurs through activation of monoaminergic neurotransmission in descending inhibitory systems. To test this hypothesis, we induced peripheral nerve injury (PNI) by crushing the sciatic nerve. The exercise intervention consisted of low-intensity treadmill running for 2 weeks immediately after injury. Animals with PNI showed an increase in pain-like behaviors that were reduced by treadmill running. Reduction of serotonin (5-hydroxytryptamine) synthesis using the tryptophan hydroxylase inhibitor para-chlorophenylalanine methyl ester prevented the analgesic effect of exercise. However, blockade catecholamine synthesis with the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine had no effect. In parallel, 2 weeks of exercise increased brainstem levels of the 5-HT and its metabolites (5-hydroxyindoleacetic acid), decreased expression of the serotonin transporter, and increased expression of 5-HT receptors (5HT-1B, 2A, 2C). Finally, PNI-induced increase in inflammatory cytokines, tumor necrosis factor-alpha, and interleukin-1 beta, in the brainstem, was reversed by 2 weeks of exercise. These findings provide new evidence indicating that low-intensity aerobic treadmill exercise suppresses pain-like behaviors in animals with neuropathic pain by enhancing brainstem 5-HT neurotransmission. These data provide a rationale for the analgesia produced by exercise to provide an alternative approach to the treatment of chronic neuropathic pain. |
Databáze: | OpenAIRE |
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