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Journal ArticleDOI

Sensory defunctionalization induced by 8% topical capsaicin treatment in a model of ultraviolet-B-induced cutaneous hyperalgesia.

24 Jul 2021-Experimental Brain Research (Springer Berlin Heidelberg)-Vol. 239, Iss: 9, pp 2873-2886
TL;DR: In this article, the authors explored the contribution of capsaicin-sensitive nociceptors in the development of mechanical and heat hyperalgesia in humans following ultraviolet-B (UVB) irradiation.
Abstract: Subpopulations of primary nociceptors (C- and Aδ-fibers), express the TRPV1 receptor for heat and capsaicin. During cutaneous inflammation, these afferents may become sensitized, leading to primary hyperalgesia. It is known that TRPV1+ nociceptors are involved in heat hyperalgesia; however, their involvement in mechanical hyperalgesia is unclear. This study explored the contribution of capsaicin-sensitive nociceptors in the development of mechanical and heat hyperalgesia in humans following ultraviolet-B (UVB) irradiation. Skin areas in 18 healthy volunteers were randomized to treatment with 8% capsaicin/vehicle patches for 24 h. After patches removal, one capsaicin-treated area and one vehicle area were irradiated with 2xMED (minimal erythema dose) of UVB. 1, 3 and 7 days post-UVB exposure, tests were performed to evaluate the development of UVB-induced cutaneous hyperalgesia: thermal detection and pain thresholds, pain sensitivity to supra-threshold heat stimuli, mechanical pain threshold and sensitivity, touch pleasantness, trans-epidermal water loss (TEWL), inflammatory response, pigmentation and micro-vascular reactivity. Capsaicin pre-treatment, in the UVB-irradiated area (Capsaicin + UVB area), increased heat pain thresholds (P 0.2). No effects of capsaicin were reported on touch pleasantness (P = 1), TEWL (P = 0.31), inflammatory response and pigmentation (P > 0.3) or micro-vascular reactivity (P > 0.8) in response to the UVB irradiation. 8% capsaicin ablation predominantly defunctionalizes TRPV1+-expressing cutaneous nociceptors responsible for heat pain transduction, suggesting that sensitization of these fibers is required for development of heat hyperalgesia following cutaneous UVB-induced inflammation but they are likely only partially necessary for the establishment of robust primary mechanical hyperalgesia.
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Journal ArticleDOI
TL;DR: A review of the state of the science for both cyclic vomiting syndrome and cannabis hyperemesis syndrome along with a discussion of the relationship between these 2 conditions can be found in this paper .
Abstract: This article provides a narrative review of the state of the science for both cyclic vomiting syndrome and cannabis hyperemesis syndrome along with a discussion of the relationship between these 2 conditions. The scope of this review includes the historical context of these conditions as well as the prevalence, diagnostic criteria, pathogenesis, and treatment strategies for both conditions. A synopsis of the endocannabinoid system provides a basis for the hypothesis that a lack of cannabidiol in modern high-potency Δ 9 -tetrahydrocannabinol cannabis may be contributory to cannabis hyperemesis syndrome and possibly other cannabis use disorders. In concluding assessment, though the publications addressing both adult cyclic vomiting syndrome and cannabis hyperemesis syndrome are steadily increasing overall, the state of the science supporting the treatments, prognosis, etiology, and confounding factors (including cannabis use) is of moderate quality. Much of the literature portrays these conditions separately and as such sometimes fails to account for the confounding of adult cyclic vomiting syndrome with cannabis hyperemesis syndrome. The diagnostic and therapeutic approaches are, at present, based generally on case series publications and expert opinion, with a very limited number of randomized controlled trials and a complete absence of Level 1 evidence within the cyclic vomiting literature overall as well as for cannabis hyperemesis syndrome specifically.
References
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Journal ArticleDOI
01 Sep 1998-Neuron
TL;DR: It is shown that protons decrease the temperature threshold for VR1 activation such that even moderately acidic conditions (pH < or = 5.9) activate VR1 at room temperature, and VR1 can be viewed as a molecular integrator of chemical and physical stimuli that elicit pain.

2,959 citations

Journal ArticleDOI
01 Aug 2006-Pain
TL;DR: Application of this standardized QST protocol in patients and human surrogate models will allow to infer underlying mechanisms from somatosensory phenotypes as well as judge plus or minus signs in patients.
Abstract: The nationwide multicenter trials of the German Research Network on Neuropathic Pain (DFNS) aim to characterize the somatosensory phenotype of patients with neuropathic pain. For this purpose, we have implemented a standardized quantitative sensory testing (QST) protocol giving a complete profile for one region within 30 min. To judge plus or minus signs in patients we have now established age- and gender-matched absolute and relative QST reference values from 180 healthy subjects, assessed bilaterally over face, hand and foot. We determined thermal detection and pain thresholds including a test for paradoxical heat sensations, mechanical detection thresholds to von Frey filaments and a 64 Hz tuning fork, mechanical pain thresholds to pinprick stimuli and blunt pressure, stimulus/response-functions for pinprick and dynamic mechanical allodynia, and pain summation (wind-up ratio). QST parameters were region specific and age dependent. Pain thresholds were significantly lower in women than men. Detection thresholds were generally independent of gender. Reference data were normalized to the specific group means and variances (region, age, gender) by calculating z-scores. Due to confidence limits close to the respective limits of the possible data range, heat hypoalgesia, cold hypoalgesia, and mechanical hyperesthesia can hardly be diagnosed. Nevertheless, these parameters can be used for group comparisons. Sensitivity is enhanced by side-to-side comparisons by a factor ranging from 1.1 to 2.5. Relative comparisons across body regions do not offer advantages over absolute reference values. Application of this standardized QST protocol in patients and human surrogate models will allow to infer underlying mechanisms from somatosensory phenotypes.

2,030 citations

Journal ArticleDOI
05 Dec 2007-Pain
TL;DR: Patients with neuropathic pain are challenging to manage and evidence‐based clinical recommendations for pharmacologic management are needed, and medications should be individualized, considering side effects, potential beneficial or deleterious effects on comorbidities, and whether prompt onset of pain relief is necessary.
Abstract: Patients with neuropathic pain (NP) are challenging to manage and evidence-based clinical recommendations for pharmacologic management are needed. Systematic literature reviews, randomized clinical trials, and existing guidelines were evaluated at a consensus meeting. Medications were considered for recommendation if their efficacy was supported by at least one methodologically-sound, randomized clinical trial (RCT) demonstrating superiority to placebo or a relevant comparison treatment. Recommendations were based on the amount and consistency of evidence, degree of efficacy, safety, and clinical experience of the authors. Available RCTs typically evaluated chronic NP of moderate to severe intensity. Recommended first-line treatments include certain antidepressants (i.e., tricyclic antidepressants and dual reuptake inhibitors of both serotonin and norepinephrine), calcium channel alpha2-delta ligands (i.e., gabapentin and pregabalin), and topical lidocaine. Opioid analgesics and tramadol are recommended as generally second-line treatments that can be considered for first-line use in select clinical circumstances. Other medications that would generally be used as third-line treatments but that could also be used as second-line treatments in some circumstances include certain antiepileptic and antidepressant medications, mexiletine, N-methyl-D-aspartate receptor antagonists, and topical capsaicin. Medication selection should be individualized, considering side effects, potential beneficial or deleterious effects on comorbidities, and whether prompt onset of pain relief is necessary. To date, no medications have demonstrated efficacy in lumbosacral radiculopathy, which is probably the most common type of NP. Long-term studies, head-to-head comparisons between medications, studies involving combinations of medications, and RCTs examining treatment of central NP are lacking and should be a priority for future research.

1,962 citations

Journal ArticleDOI
TL;DR: The results suggest that itching during inflammatory skin diseases such as atopic dermatitis is linked to a distinct itch-generating type, and demonstrate single-cell RNA-seq as an effective strategy for dissecting sensory responsive cells into distinct neuronal types.
Abstract: The primary sensory system requires the integrated function of multiple cell types, although its full complexity remains unclear. We used comprehensive transcriptome analysis of 622 single mouse neurons to classify them in an unbiased manner, independent of any a priori knowledge of sensory subtypes. Our results reveal eleven types: three distinct low-threshold mechanoreceptive neurons, two proprioceptive, and six principal types of thermosensitive, itch sensitive, type C low-threshold mechanosensitive and nociceptive neurons with markedly different molecular and operational properties. Confirming previously anticipated major neuronal types, our results also classify and provide markers for new, functionally distinct subtypes. For example, our results suggest that itching during inflammatory skin diseases such as atopic dermatitis is linked to a distinct itch-generating type. We demonstrate single-cell RNA-seq as an effective strategy for dissecting sensory responsive cells into distinct neuronal types. The resulting catalog illustrates the diversity of sensory types and the cellular complexity underlying somatic sensation.

1,609 citations

Journal ArticleDOI
01 Apr 1999-Nature
TL;DR: It is proposed that responses to noxious heat involve these related, but distinct, ion-channel subtypes that together detect a range of stimulus intensities.
Abstract: Pain-producing heat is detected by several classes of nociceptive sensory neuron that differ in their thermal response thresholds. The cloned capsaicin receptor, also known as the vanilloid receptor subtype 1 (VR1), is a heat-gated ion channel that has been proposed to mediate responses of small-diameter sensory neurons to moderate (43 degrees C) thermal stimuli. VR1 is also activated by protons, indicating that it may participate in the detection of noxious thermal and chemical stimuli in vivo. Here we identify a structurally related receptor, VRL-1, that does not respond to capsaicin, acid or moderate heat. Instead, VRL-1 is activated by high temperatures, with a threshold of approximately 52 degrees C. Within sensory ganglia, VRL-1 is most prominently expressed by a subset of medium- to large-diameter neurons, making it a candidate receptor for transducing high-threshold heat responses in this class of cells. VRL-1 transcripts are not restricted to the sensory nervous system, indicating that this channel may be activated by stimuli other than heat. We propose that responses to noxious heat involve these related, but distinct, ion-channel subtypes that together detect a range of stimulus intensities.

1,500 citations