Long-term anti-itch effect of botulinum neurotoxin A is associated with downregulation of TRPV1 and TRPA1 in the dorsal root ganglia in mice

Cao, Lei-Fang; Si, Meng; Huang, Ya; Chen, Li‐Hua; Peng, Xiaoyan; Qin, Yaqin; Liu, Tengteng; Zhou, Yan; Liu, Tong; Luo, Weifeng

doi:10.1097/wnr.0000000000000779

Cited by 20 publications

(25 citation statements)

References 24 publications

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“…TRPV1 could be activated by various endogenous and exogenous stimuli, including capsaicin, temperature, pH, TNF-α, and pro-inflammatory cytokines and amplified the effects of inflammation [39,58]. Recent studies show that dry skin stimuli increased the expression of TRPV1 in DRG and TG neurons [59,60]. Combined with our above results, we speculate that NLRP1 inflammasome could contribute to the upregulation of TRPV1 in dry skin induced chronic itch model.…”

Section: Discussionsupporting

confidence: 79%

Spinal cord NLRP1 inflammasome contributes to dry skin induced chronic itch in mice

Fan

Gao

Song

et al. 2020

J Neuroinflammation

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Background: Dry skin itch is one of the most common skin diseases and elderly people are believed to be particularly prone to it. The inflammasome has been suggested to play an important role in chronic inflammatory disorders including inflammatory skin diseases such as psoriasis. However, little is known about the role of NLRP1 inflammasome in dry skin-induced chronic itch. Methods: Dry skin-induced chronic itch model was established by acetone-ether-water (AEW) treatment. Spontaneous scratching behavior was recorded by video monitoring. The expression of nucleotide oligomerization domain (NOD)-like receptor protein 1 (NLRP1) inflammasome complexes, transient receptor potential vanilloid type 1 (TRPV1), and the level of inflammatory cytokines were determined by western blot, quantitative real-time PCR, and enzyme-linked immunosorbent assay (ELISA) kits. Nlrp1a knockdown was performed by an adeno-associated virus (AAV) vector containing Nlrp1a-shRNA-eGFP infusion. H.E. staining was used to evaluate skin lesion. Results: AEW treatment triggers spontaneous scratching and significantly increases the expression of NLRP1, ASC, and caspase-1 and the levels of IL-1β, IL-18, IL-6, and TNF-α in the spinal cord and the skin of mice. Spinal cord Nlrp1a knockdown prevents AEW-induced NLRP1 inflammasome assembly, TRPV1 channel activation, and spontaneous scratching behavior. Capsazepine, a specific antagonist of TRPV1, can also inhibit AEW-induced inflammatory response and scratching behavior. Furthermore, elderly mice and female mice exhibited more significant AEW-induced scratching behavior than young mice and male mice, respectively. Interestingly, AEW-induced increases in the expression of NLRP1 inflammasome complex and the levels of inflammatory cytokines were more remarkable in elderly mice and female mice than in young mice and male mice, respectively. Conclusions: Spinal cord NLRP1 inflammasome-mediated inflammatory response contributes to dry skin-induced chronic itch by TRPV1 channel, and it is also involved in age and sex differences of chronic itch. Inhibition of NLRP1 inflammasome may offer a new therapy for dry skin itch.

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Section: Discussionsupporting

confidence: 79%

Spinal cord NLRP1 inflammasome contributes to dry skin induced chronic itch in mice

Fan

Gao

Song

et al. 2020

J Neuroinflammation

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“…16,17 Accordingly, Na V 1.7, TRPV1, and TRPA1 are potential therapeutic targets for itch management. 17,18…”

Section: Pathways Of Itchmentioning

confidence: 99%

Itch: From mechanism to (novel) therapeutic approaches

Yosipovitch

Rosen

Hashimoto

2018

Journal of Allergy and Clinical Immunology

246

307

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Itch is a common sensory experience that is prevalent in patients with inflammatory skin diseases, as well as in those with systemic and neuropathic conditions. In patients with these conditions, itch is often severe and significantly affects quality of life. Itch is encoded by 2 major neuronal pathways: histaminergic (in acute itch) and nonhistaminergic (in chronic itch). In the majority of cases, crosstalk existing between keratinocytes, the immune system, and nonhistaminergic sensory nerves is responsible for the pathophysiology of chronic itch. This review provides an overview of the current understanding of the molecular, neural, and immune mechanisms of itch: beginning in the skin, proceeding to the spinal cord, and eventually ascending to the brain, where itch is processed. A growing understanding of the mechanisms of chronic itch is expanding, as is our pipeline of more targeted topical and systemic therapies. Our therapeutic armamentarium for treating chronic itch has expanded in the last 5 years, with developments of topical and systemic treatments targeting the neural and immune systems.

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“…Additionally, it inhibited mast cell degranulation and the release of pruritogenic mediators in both human and murine mast cells, with inhibition of mast cell‐dependent and ‐independent scratching behavior in pretreated mice 25 . It downregulated the expression of the itch receptors’ transient receptor potential cation channel, subfamily A, member 1 (TRPA1) and subfamily V, member 1 (TRPV1), in the dorsal root ganglia in a mouse model of chronic dry itch leading to long‐term amelioration of itching 26 . The above actions can explain its antipruritic effects in our cases which are independent of the antiperspirant effect of the toxin.…”

Section: Discussionmentioning

confidence: 99%

Botulinum toxin type A in chronic non‐dyshidrotic palmar eczema: A side‐by‐side comparative study

Ismail

El-Kholy

Farid

2020

The Journal of Dermatology

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New indications are being reported for intradermal botulinum toxin type A (BTX-A) owing to its anti-inflammatory and antipruritic actions. Its successful use for dyshidrotic hand eczema and lichen simplex has been reported in a few cases, while its utility in dry palmar eczema not associated with hyperhidrosis has not yet been investigated. The aim of this study was the assessment of the additive efficacy and tolerability of BTX-A in chronic dry palmar eczema. This prospective non-randomized side-by-side comparative study included 30 cases of chronic bilateral dry palmar eczema with no associated hyperhidrosis. Combined emollients and topical mid-potency steroid on one side were compared with an additive 100 units of intradermal BTX-A on the other side for efficacy and tolerability using both patient-and physician-oriented scores over a period of 6 months. Timing and extent of improvement and relapse were recorded on both sides, together with the frequency of development of side-effects. Both lines were effective and well tolerated, with significantly greater reduction of symptom and sign scores and higher overall patient satisfaction on the side receiving BTX-A, an effect which lasted for a significantly longer duration on this side (4 months) as compared with the other side (1 month). In conclusion, intradermal BTX-A at a dose of 100 units/palm is beneficial and well tolerated in chronic dry palmar eczema. Compared with topical steroid and emollients alone, its addition yielded superior efficacy that was longer lasting and more satisfactory to the patients, while exerting a steroid-sparing effect.

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Long-term anti-itch effect of botulinum neurotoxin A is associated with downregulation of TRPV1 and TRPA1 in the dorsal root ganglia in mice

Cited by 20 publications

References 24 publications

Spinal cord NLRP1 inflammasome contributes to dry skin induced chronic itch in mice

Spinal cord NLRP1 inflammasome contributes to dry skin induced chronic itch in mice

Itch: From mechanism to (novel) therapeutic approaches

Botulinum toxin type A in chronic non‐dyshidrotic palmar eczema: A side‐by‐side comparative study

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