LPA1 receptor involvement in fibromyalgia-like pain induced by intermittent psychological stress, empathy
Treatment for fibromyalgia is an unmet medical need and its pathogenesis is still poorly understood. The present study demonstrated that intermittent psychological stress (IPS), or empathy causes generalized chronic abnormal pain with female predominance. The persistence of the pain phenotype was de...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-01-01
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| Series: | Neurobiology of Pain |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452073X1730003X |
| _version_ | 1818345427637895168 |
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| author | Hiroshi Ueda Hiroyuki Neyama |
| author_facet | Hiroshi Ueda Hiroyuki Neyama |
| author_sort | Hiroshi Ueda |
| collection | DOAJ |
| description | Treatment for fibromyalgia is an unmet medical need and its pathogenesis is still poorly understood. The present study demonstrated that intermittent psychological stress (IPS), or empathy causes generalized chronic abnormal pain with female predominance. The persistence of the pain phenotype was dependent on the unpredictability of the stressor. The pain was reversed by pregabalin (PGB), duloxetine (DLX) or mirtazapine (Mir), but not by diclofenac or morphine. Differential administration of these existing medicines revealed that the sites of PGB and Mir actions exist in the brain, but not in the spinal cord, while that of DLX is preferentially in the spinal cord. It is interesting to note that the intracerebroventricular injection of PGB or Mir showed potent analgesia for 24 h or longer, though systemic injection of these medicines shows anti-hyperalgesia just for several hours. These results indicate that initial intense actions in the target brain may prevent the forthcoming development of pain memory. IPS-induced abnormal pain was prevented in mice deficient of lysophosphatidic acid receptor 1 (LPA1) gene, and completely cured by the repeated intrathecal treatments with LPA1 antagonist, AM966, which did not show acute action. All these results suggest that IPS model is an experimental animal model, which mimics the pathophysiology and pharmacotherapy in fibromyalgia in clinic, and LPA1 signaling plays crucial roles in the IPS-induced fibromyalgia-like abnormal pain. Keywords: Fibromyalgia, Empathy, Psychological stress, Mirtazapine, Morphine, Lysophosphatidic acid |
| first_indexed | 2024-12-13T17:02:12Z |
| format | Article |
| id | doaj.art-5418e568104b4fa6b7fff5d1b49c0e6a |
| institution | Directory Open Access Journal |
| issn | 2452-073X |
| language | English |
| last_indexed | 2024-12-13T17:02:12Z |
| publishDate | 2017-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Pain |
| spelling | doaj.art-5418e568104b4fa6b7fff5d1b49c0e6a2022-12-21T23:37:47ZengElsevierNeurobiology of Pain2452-073X2017-01-0111625LPA1 receptor involvement in fibromyalgia-like pain induced by intermittent psychological stress, empathyHiroshi Ueda0Hiroyuki Neyama1Corresponding author at: Department of Pharmacology and Therapeutic Innovation, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.; Department of Pharmacology and Therapeutic Innovation, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Pharmacology and Therapeutic Innovation, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanTreatment for fibromyalgia is an unmet medical need and its pathogenesis is still poorly understood. The present study demonstrated that intermittent psychological stress (IPS), or empathy causes generalized chronic abnormal pain with female predominance. The persistence of the pain phenotype was dependent on the unpredictability of the stressor. The pain was reversed by pregabalin (PGB), duloxetine (DLX) or mirtazapine (Mir), but not by diclofenac or morphine. Differential administration of these existing medicines revealed that the sites of PGB and Mir actions exist in the brain, but not in the spinal cord, while that of DLX is preferentially in the spinal cord. It is interesting to note that the intracerebroventricular injection of PGB or Mir showed potent analgesia for 24 h or longer, though systemic injection of these medicines shows anti-hyperalgesia just for several hours. These results indicate that initial intense actions in the target brain may prevent the forthcoming development of pain memory. IPS-induced abnormal pain was prevented in mice deficient of lysophosphatidic acid receptor 1 (LPA1) gene, and completely cured by the repeated intrathecal treatments with LPA1 antagonist, AM966, which did not show acute action. All these results suggest that IPS model is an experimental animal model, which mimics the pathophysiology and pharmacotherapy in fibromyalgia in clinic, and LPA1 signaling plays crucial roles in the IPS-induced fibromyalgia-like abnormal pain. Keywords: Fibromyalgia, Empathy, Psychological stress, Mirtazapine, Morphine, Lysophosphatidic acidhttp://www.sciencedirect.com/science/article/pii/S2452073X1730003X |
| spellingShingle | Hiroshi Ueda Hiroyuki Neyama LPA1 receptor involvement in fibromyalgia-like pain induced by intermittent psychological stress, empathy Neurobiology of Pain |
| title | LPA1 receptor involvement in fibromyalgia-like pain induced by intermittent psychological stress, empathy |
| title_full | LPA1 receptor involvement in fibromyalgia-like pain induced by intermittent psychological stress, empathy |
| title_fullStr | LPA1 receptor involvement in fibromyalgia-like pain induced by intermittent psychological stress, empathy |
| title_full_unstemmed | LPA1 receptor involvement in fibromyalgia-like pain induced by intermittent psychological stress, empathy |
| title_short | LPA1 receptor involvement in fibromyalgia-like pain induced by intermittent psychological stress, empathy |
| title_sort | lpa1 receptor involvement in fibromyalgia like pain induced by intermittent psychological stress empathy |
| url | http://www.sciencedirect.com/science/article/pii/S2452073X1730003X |
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