Gene/Protein
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Drug
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Gene/Protein
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Target Concepts:
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Query: UMLS:C0033774 (
pruritus
)
14,546
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Itch
is a common symptom in patients with skin and systemic diseases, but the effective treatment is limited. Here, we evaluated the anti-
itch
effects of the botulinum toxin type A (
BoNT/A
) using acute and chronic dry skin
itch
mouse models, which were induced by compound 48/80, chloroquine, and a mixture of acetone-diethylether-water treatment, respectively. Pretreatment of intradermal
BoNT/A
exerted long-term inhibitory effects on compound 48/80-induced and chloroquine-induced acute
itch
on days 1, 3, 7, and 14, but not on day 21, in mice. Furthermore, a single injection of
BoNT/A
reduced the expression of the transient receptor potential cation channel, subfamily V, member 1 (TRPV1), and the transient receptor potential cation channel, subfamily A, member 1 (TRPA1) at both transcriptional and translational levels in the dorsal root ganglia (DRG) in mice. Pretreatment of
BoNT/A
also attenuated chronic
itch
induced by acetone-diethylether-water treatment and abolished the upregulation of TRPA1 in the DRG. Thus, it was suggested that downregulation of the expression of TRPA1 and TRPV1 in the DRG may contribute toward the long-term anti-
itch
effects of a single injection of
BoNT/A
in mice and
BoNT/A
treatment may serve as an alternative strategy for anti-
itch
therapy.
...
PMID:Long-term anti-itch effect of botulinum neurotoxin A is associated with downregulation of TRPV1 and TRPA1 in the dorsal root ganglia in mice. 2841 Feb 68
The antinociceptive action of botulinum toxin type A (
BoNT/A
) has been demonstrated in behavioral animal studies and clinical settings. It was shown that this effect is associated with toxin activity in CNS, however, the mechanism is not fully understood. Substance P (SP) is one of the dominant neurotransmitters in primary afferent neurons transmitting pain and
itch
. Thus, here we examined association of SP-mediated transmission and
BoNT/A
antinociceptive action by employing gene knockouts. Antinociceptive activity of intraplantarly (i.pl.) injected
BoNT/A
was examined in mice lacking the gene encoding for SP/neurokinin A (tac1
-/-
) or SP-preferred receptor neurokinin 1 (tac1r
-/-
), compared to control C57Bl/6J wild type animals.
BoNT/A
action was assessed in inflammatory pain induced by formalin and CFA, and neuropathic pain induced by partial sciatic nerve ligation.
BoNT/A
activity in CNS was examined by c-Fos and
BoNT/A
-cleaved SNAP-25 immunohistochemistry. In wild type mice, acute (formalin-evoked) and chronic pain (neuropathic and inflammatory) was reduced by peripherally injected
BoNT/A
. In tac1
-/-
and tac1r
-/-
knockout mice,
BoNT/A
exerted no analgesic effect. In control animals
BoNT/A
reduced the formalin-evoked c-Fos expression in lumbar dorsal horn, while in knockout mice the c-Fos expression was not reduced. After peripheral toxin injection, cleaved SNAP-25 occurred in lumbar dorsal horn in all animal genotypes.
BoNT/A
antinociceptive activity is absent in animals lacking the SP and neurokinin 1 receptor encoding genes, in spite of presence of toxin's enzymatic activity in central sensory regions. Thus, we conclude that the integrity of SP-ergic system is necessary for the antinociceptive activity of
BoNT/A
.
...
PMID:Involvement of substance P in the antinociceptive effect of botulinum toxin type A: Evidence from knockout mice. 2867 22
