Pain
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Methylglyoxal (MGO) is a reactive glycolytic metabolite associated with painful diabetic neuropathy at plasma concentrations between 500 nM and 5 μM. The mechanisms through which MGO causes neuropathic pain at these pathological concentrations are not known. Because MGO has been linked to diabetic neuropathic pain, which is prevalent and poorly treated, insight into this unsolved biomedical problem could lead to much needed therapeutics. ⋯ Blocking the integrated stress response with a specific inhibitor (ISRIB) strongly attenuates and reverses MGO-evoked pain. Moreover, ISRIB reduces neuropathic pain induced by diabetes in both mice and rats. Our work elucidates the mechanism of action of MGO in the production of pain at pathophysiologically relevant concentrations and suggests a new pharmacological avenue for the treatment of diabetic and other types of MGO-driven neuropathic pain.
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Review
The IASP classification of chronic pain for ICD-11: chronic secondary headache or orofacial pain.
This article describes chronic secondary headache and chronic orofacial pain (OFP) disorders with respect to the new International Classification of Diseases (ICD-11). The section refers extensively to the International Classification of Headache Disorders (ICHD-3) of the International Headache Society that is implemented in the chapter on Neurology in ICD-11. The ICHD-3 differentiates between primary (idiopathic) headache disorders, secondary (symptomatic) headache disorders, and OFP disorders including cranial neuralgias. ⋯ The subdivisions of chronic secondary OFP of ICHD-3 are complemented by the Diagnostic Criteria for Temporomandibular Disorders and contributions from the International Association for the Study of Pain Special Interest Group on Orofacial and Head Pain and include chronic dental pain. The ICD-11 codes described here are intended to be used in combination with codes for the underlying diseases, to identify patients who require specialized pain management. In addition, these codes shall enhance visibility of these disorders in morbidity statistics and motivate research into their mechanisms.
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The International Classification of Diseases, 11th Revision (ICD-11), proposes, for the first time, a coding system for chronic pain. This system contains 1 code for "chronic primary pain," where chronic pain is the disease, and 6 codes for chronic secondary pain syndromes, where pain developed in the context of another disease. This provides the opportunity for routine, standardised coding of chronic pain throughout all health care systems. ⋯ Chronic pain will be recognized as a centrally important condition in primary care. The capacity to measure incidence, prevalence, and impact will help in identification of human, financial, and educational needs required to address chronic pain in primary care. Finally, opportunities to match evidence-based treatment pathways to distinct chronic pain subtypes will be enhanced.
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Nerve injury-induced neuropathic pain is difficult to treat. In this study, we used exosomes derived from human umbilical cord mesenchymal stem cell (UCMSC) as a cell-free therapy for nerve injury-induced pain in rats. Isolated UCMSC exosomes range in size from 30 to 160 nm and contain CD63, HSP60, and CD81 exosome markers. ⋯ Exosomes also inhibited the level of TNF-α and IL-1β, while enhanced the level of IL-10, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor in the ipsilateral L5/6 dorsal root ganglion of nerve-ligated rats, indicating anti-inflammatory and proneurotrophic abilities. Protein analysis revealed the content of vascular endothelial growth factor C, angiopoietin-2, and fibroblast growth factor-2 in the exosomes. In summary, intrathecal infusion of exosomes from UCMSCs may be considered as a novel therapeutic approach for nerve injury-induced pain.
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Chronic visceral pain is a frequent and disabling condition. Despite high prevalence and impact, chronic visceral pain is not represented in ICD-10 in a systematic manner. Chronic secondary visceral pain is chronic pain secondary to an underlying condition originating from internal organs of the head or neck region or of the thoracic, abdominal, or pelvic regions. ⋯ This article describes how a new classification of chronic secondary visceral pain is intended to facilitate the diagnostic process and to enable the collection of accurate epidemiological data. Furthermore, it is hoped that the new classification will improve the tailoring of patient-centered pain treatment of chronic secondary visceral pain and stimulate research. Chronic secondary visceral pain should be distinguished from chronic primary visceral pain states that are considered diseases in their own right.