Dose–response study of topical allyl isothiocyanate (mustard oil) as a human surrogate model of pain, hyperalgesia, and neurogenic inflammation

Abstract: Despite being a ubiquitous animal pain model, the natural TRPA1-agonist allyl isothiocyanate (AITC, also known as “mustard oil”) has only been sparsely investigated as a potential human surrogate model of pain, sensitization, and neurogenic inflammation. Its dose–response as an algogenic, sensitizing irritant remains to be elucidated in human skin. Three concentrations of AITC (10%, 50%, and 90%) and vehicle (paraffin) were applied for 5 minutes to 3 × 3 cm areas on the volar forearms in 14 healthy volunteers, and evoked pain intensity (visual analog scale 0-100 mm) and pain quality were assessed. In addition, a comprehensive battery of quantitative sensory tests was conducted, including assessment of mechanical and thermal sensitivity. Neurogenic inflammation was quantified using full-field laser perfusion imaging. Erythema and hyperpigmentation were assessed before, immediately after, and ≈64 hours after AITC exposure. AITC induced significant dose-dependent, moderate-to-severe spontaneous burning pain, mechanical and heat hyperalgesia, and dynamic mechanical allodynia (P 10% and ≤50%. The model is translatable to humans and could be useful in pharmacological proof-of-concept studies of TRPA1-antagonists, analgesics, and anti-inflammatory compounds or for exploratory clinical purposes, eg, loss- or gain-of-function in peripheral neuropathies.
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research

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Publication date: 19 November 2019Source: Cell Reports, Volume 29, Issue 8Author(s): Hao Luo, Hui-Zhu Liu, Wen-Wen Zhang, Megumi Matsuda, Ning Lv, Gang Chen, Zhen-Zhong Xu, Yu-Qiu ZhangSummaryThe proinflammatory cytokine interleukin-17 (IL-17) is implicated in pain regulation. However, the synaptic mechanisms by which IL-17 regulates pain transmission are unknown. Here, we report that glia-produced IL-17 suppresses inhibitory synaptic transmission in the spinal cord pain circuit and drives chemotherapy-induced neuropathic pain. We find that IL-17 not only enhances excitatory postsynaptic currents (EPSCs) but also suppresse...
Source: Cell Reports - Category: Cytology Source Type: research
Homocysteinemia is a metabolic condition characterized by abnormally high level of homocysteine in the blood and is considered to be a risk factor for peripheral neuropathy. However, the cellular mechanisms underlying toxic effects of homocysteine on the processing of peripheral nociception have not yet been investigated comprehensively. Here, using a rodent model of experimental homocysteinemia, we report the causal association between homocysteine and the development of mechanical allodynia. Homocysteinemia-induced mechanical allodynia was reversed on pharmacological inhibition of T-type calcium channels. In addition, ou...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse side effect of cancer treatment with no Food and Drug Administration-approved medication for its prevention or management. Using RNA sequencing analysis of dorsal root ganglia (DRG), we identify critical contributions of histone deacetylase 6 (HDAC6) and mitochondrial damage to the establishment of CIPN in a mouse model of cisplatin-induced neuropathy. We show that pharmacological inhibition of HDAC6 using ACY-1215 or global deletion of HDAC6 is sufficient to prevent cisplatin-induced mechanical allodynia, loss of intraepidermal nerve fibers (IENFs), an...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
ConclusionOur findings indicate a nonlinear relationship between Burst ‐DRGS amplitude and behavioral outcome, with an estimated optimal amplitude of 52% MT. Further optimization and analysis of DRGS driven by insights into the underlying mechanisms related to the various stimulation paradigms is warranted.
Source: Neuromodulation: Technology at the Neural Interface - Category: Biotechnology Authors: Tags: Basic Research Source Type: research
Publication date: Available online 11 November 2019Source: Neuroscience LettersAuthor(s): Bingjie Qin, Yuxing Li, Xiaohu Liu, Denghui Gong, Weihong ZhengAbstarctChemotherapy-induced peripheral neuropathy (CIPN) has a adverse impact to the living quality of cancer patients. This side effect of CIPN limit the dose of drug used in many chemotherapies, such as vincristine (VCR). The activation of microglia in the spinal dorsal horn is involved in the occurrence and development of neuropathic pain induced by VCR. Recent study has demonstrated that hypoxia induced microglia activation depends on Notch signaling, and it is involv...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research
CONCLUSION: GLA treatment in patients with painful DPN was noninferior to ALA in terms of reducing pain intensity measured by the VAS over 12 weeks. PMID: 31701699 [PubMed - as supplied by publisher]
Source: Diabetes and Metabolism Journal - Category: Endocrinology Tags: Diabetes Metab J Source Type: research
Publication date: November 2019Source: The Journal of Foot and Ankle Surgery, Volume 58, Issue 6Author(s): James Stimpson, Damien F. Gill, Arman Memarzadeh, Mike Dunne, Laura Perry, Ahmed Magan, Adam Devany, Chandra PasapulaAbstractWe evaluated whether moving the “line of crush” from thigh to the calf before onset of tourniquet-mediated hypertension would prevent or diminish it. We also evaluated any change in pain or functional outcome. Twenty adult patients were recruited and randomly assigned to either control or intervention groups. Inclusion criteria: any willing participant>18 years old with foot and/o...
Source: The Journal of Foot and Ankle Surgery - Category: Orthopaedics Source Type: research
Condition:   Diabetic Peripheral Neuropathic Pain Interventions:   Drug: NYX-2925 50 mg;   Drug: Placebo Sponsors:   Aptinyx;   Syneos Health Not yet recruiting
Source: - Category: Research Source Type: clinical trials
​BY JENNIFER TUONG; IVAN KHARCHENKO; JEAN LUC AGARD; &AHMED RAZIUDDIN, MDA 65-year-old man who had HIV well-controlled with highly active antiretroviral therapy, hypertension, sciatica, and restless leg syndrome presented to the emergency department with left leg pain. He also had had chemotherapy and radiation for anal cancer. The patient said the pain had started 45 minutes earlier when he was sitting on the toilet.He described the pain as sore in quality and 10/10 on the pain scale. He reported that it had started in his lower back and radiated to his left leg. He said he had had no trauma or weakness to the regio...
Source: The Case Files - Category: Emergency Medicine Tags: Blog Posts Source Type: research
Conclusions: The GPM accounts for signs and symptom presentations in DCS. This provides the basis for appropriate treatments and logical recommendations for return to diving. We recommend that the label "unexplained DCS" be discontinued and that the GPM be used to determine the cause. Once the cause is established, "DCS due to disordered decompression" becomes the appropriate term. PMID: 30028916 [PubMed - in process]
Source: Undersea and Hyperbaric Medicine - Category: Sports Medicine Authors: Tags: Undersea Hyperb Med Source Type: research
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