High-Concentration L-Menthol Exhibits Counter-Irritancy to Neurogenic Inflammation, Thermal and Mechanical Hyperalgesia Caused by Trans-cinnamaldehyde

Andersen, Hjalte Holm; Gazerani, Parisa; Arendt-Nielsen, Lars

doi:10.1016/j.jpain.2016.05.004

Cited by 36 publications

(30 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This corresponds to the prevailing notion of these fibers being myelinated cold Aδfibers and warmth-selective C-fibers, respectively [14]. While the effect of AITC-induced TRPA1-activation on thermal detection thresholds have not previously been assessed, the present results do correspond to findings stemming from the trans-cinnamaldehyde model, which similarly have no, or very limited effects on thermal detection thresholds [2,58,61]. Oppositely, CPT was decreased by the 90% AITC concentration signifying cold hypoalgesia and a similar, but insignificant trend was observed for 50%.…”

Section: Thermal Sensory Sensitivitysupporting

confidence: 87%

“…The 9 cm 2 in which AITC was applied was then subtracted from the score thus giving rise to an estimate of the size of the secondary neurogenic inflammation or the "reflex response". This method has previously been applied to quantify the neurogenic inflammatory response to various chemical irritants [1,2,61]. The erythema (redness) and skin pigmentation were measured with a spectrometer designed for cutaneous use (ColorMeter, DSM II, Cortex Technology, Hadsund, Denmark) as previously utilized [56] .…”

Section: A C C E P T E Dmentioning

confidence: 99%

See 1 more Smart Citation

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

Andersen¹,

Vecchio²,

Gazerani³

et al. 2017

Pain

Self Cite

View full text Add to dashboard Cite

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 < 0.05). No significant differences in induced pain hypersensitivity were observed between the 50% and 90% AITC concentrations. Acute and prolonged inflammation was evoked by all concentrations, and assessments by full-field laser perfusion imaging demonstrated a significant dose-dependent increase with a ceiling effect from 50% to 90%. Topical AITC application produces pain and somatosensory sensitization in a dose-dependent manner with optimal concentrations recommended to be >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.

show abstract

Section: Thermal Sensory Sensitivitysupporting

confidence: 87%

Section: A C C E P T E Dmentioning

confidence: 99%

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

Andersen¹,

Vecchio²,

Gazerani³

et al. 2017

Pain

Self Cite

View full text Add to dashboard Cite

show abstract

“…Moreover, the histamine-evoked flare area was calculated as the area of ≥30% perfusion rate compared to the surrounding background in accordance with previously described methodology. 7,8,65 Wheal was measured by the longest diagonal and the orthogonal diagonal approximately 15 minutes after the histamine pricks were conducted in accordance with standardized recommendation for SPT. 35…”

Section: Inflammation Imaging and Wheal Measurementsmentioning

confidence: 99%

Nonhistaminergic and mechanical itch sensitization in atopic dermatitis

Andersen

Elberling

Sølvsten

et al. 2017

Pain

112

View full text Add to dashboard Cite

Chronic or episodic severe itch is recurrent in atopic dermatitis (AD). Nonhistaminergic itch pathways are suggested to dominate in AD itch, contributing to an "itch-scratch-itch cycle" that prolongs and worsens itch, pain, and skin lesions. We hypothesized that nonhistaminergic neuronal sensitization contributes to itch in AD. Hence, we compared sensitivity with thermal, mechanical, and chemical pruritic stimuli in patients with AD and controls. The study comprised 25 patients with AD with chronic itch and 25 healthy controls. Questionnaires on itch characteristics were administered, and sensory tests were conducted intralesionally, extralesionally, and in homologous areas of controls. Thermal and mechanical quantitative sensory testing (QST) as well as histamine and cowhage provocations were performed. Subsequently, hyperknesis and vasomotor reactivity were assessed. Average itch and associated pain among patients with AD were 60.7 ± 4.3 and 39.7 ± 5.2 (VAS0-100), respectively. Patients experienced significantly higher itch from cowhage both intralesionally and extralesionally compared with controls, whereas histamine-evoked itch intensity was not significantly different between groups. No group differences were found for thermal quantitative sensory testings or pain evoked by itch provocations. Patients had decreased mechanical detection thresholds intralesionally and increased mechanical pain sensitivity intralesionally and extralesionally. Lastly, patients exhibited intralesional and extralesional hyperknesis before chemical itch provocations and augmented hyperknesis after itch provocations. Increased itch in response to cowhage (but not histamine) suggests nonhistaminergic pathway-specific itch sensitization in AD, whereas increased susceptibility to mechanically evoked itch and pain, particularly intralesionally suggests sensitization of mechanosensitive circuitry not normally associated with itch. Drugs targeting the nonhistaminergic (PAR2/TRPA1) itch pathway and itch sensitization are promising for treating AD itch.

show abstract

“…In a recent study, injections of the TRPA1 agonist cinnamaldehyde into the forearm resulted in significant pain and neurogenic flare; however, simultaneous injection of menthol resulted in lower pain ratings, elevated mechanical pain thresholds, and reduced neurogenic flare as compared to cinnamaldehyde alone [17]. Two case studies also demonstrate the analgesic role of TRPM8 in patients suffering from chronic neuropathic pain.…”

Section: The Role For Trpm8 In Mechanical and Heat Analgesiamentioning

confidence: 99%