Anti-scratching Effect Research Articles

The effect of massage and topical violet oil on the severity of pruritus and dry skin in hemodialysis patients: A randomized controlled trial

BackgroundPruritus is one of the common problems in hemodialysis patients that involves more than 45% of Iranian patients. Its exact pathogenesis is unclear. Meanwhile, violet is an old plant with anti-scratching effects, which is extensively used to treat diseases in the Persian medicine. This study aimed to evaluate the effect of massaging the body with and without violet oil in the treatment of uremic pruritus. MethodsIn this study 57 hemodialysis patients who had uremic pruritus were categorized randomly into two groups. The treatment involved massage with and without topical 5 ml violet oil for 7 min during six sessions (two weeks) on the healthy hand which did not have fistula pruritus score questionnaire were completed before and after the intervention. ResultsThere was no difference between the two groups before the intervention; however, after the intervention, a significant difference was observed within each group and between the groups in terms of skin dryness score, severity, location, and frequency of pruritus, which were recovered significantly in both groups. ConclusionThe results of this study indicated that massage with violet oil is more effective than massage alone and is recommended as a complementary treatment for patients with uremic pruritis.

Loliolide Presents Antiapoptosis and Antiscratching Effects in Human Keratinocytes.

Loliolide is a monoterpenoid hydroxylactone present in freshwater algae that has anti-inflammatory and antiaging activity; however, its effects on ultraviolet-damaged skin have yet to be elucidated. This study investigated the antiapoptosis and wound-healing effects of loliolide using HaCaT cells (a human keratinocyte cell line). Loliolide inhibited the expression of reactive oxygen species (ROS) induced by ultraviolet radiation as well as wrinkle formation-related matrix metalloproteinase genes and increased the expression of the damage repair-related gene SIRT1. The apoptosis signaling pathway was confirmed by Western blot analysis, which showed that loliolide was able to reduce the expression of caspases 3, 8, and 9, which are related to ROS-induced apoptosis. In addition, Western blotting, reverse-transcription polymerase chain reaction (PCR), and real-time PCR analyses showed that loliolide enhanced the expression of the epidermal growth factor receptor signaling pathway (PI3K, AKT) and migration factors, such as K6, K16, and K17; keratinocyte growth factor; and inflammatory cytokines, such as interleukin (IL)-1, IL-17, and IL-22 expressed during the cellular scratching process, suggesting a putative wound-healing ability. Because of the antiapoptosis and antiscratching effects on skin of both loliolide and loliolide-rich Prasiola japonica ethanol extract, we consider the former to be an important compound used in the cosmeceutical industry.

P-92 - Anti-scratching effect and related antioxidant responses of aqueous crude extract from Acca sellowiana in the dry skin model

Itch is an unpleasant sensation that evokes a desire to scratch. It could be debilitating and reducing life quality. The few effective itch treatments in clinical use highlights plants as possible sources of new drugs. Acca sellowiana (O. Berg), also known as Feijoa sellowiana, is used in folk medicine in the Serrano Plateau of Santa Catarina State, Brazil. The aim of this study was to investigate the use of the aqueous crude extract from Acca sellowiana (ACEAs) leaves as a potential therapeutic agent for itch on mice Swiss, and associated antioxidant responses. Chemical composition of ACEAs includes gallic acid, catechin, and epicatechin. ACEAs drastically decreased the scratching behavior in the acetone/ether/water (AEW) dry skin model. The AEW treatment increased the activity of antioxidant enzymes superoxide dismutase (SOD), catalase, and glutathione reductase in the skin, but not glutathione peroxidase (GPx), while in the spinal cord SOD and GPx activity were decreased. These alterations in the skin and spinal cord were not clearly associated to ACEAs anti-scratching effect. This is the first report showing the effect of ACEAs in chronic experimental model of itch in mice. The antioxidant response induced by the AEW model may not be related to scratching behavior.

Effects of Intrathecal κ-Opioid Receptor Agonist on Morphine-Induced Itch and Antinociception in Mice.

The μ-opioid receptor (MOR) agonist-induced itch is a significant issue associated with analgesic therapies. Research suggested that systemically administered κ-opioid receptor (KOR) agonists inhibit intrathecal morphine-induced itch in primates. However, serious adverse effects induced by systemically administered KOR agonists may restrict their usefulness in humans. We investigated the effects of intrathecal KOR agonists on intrathecal morphine-mediated itch and antinociception in mice.Mice received intrathecal injections of one of the following drugs: morphine (0.1-1.0 nmol), the selective KOR agonist TRK-820 100 pmol, the combination of morphine 0.3 nmol + TRK-820 (10-100 pmol), and 5 μL of saline. One hour after intraperitoneal administration of the selective KOR antagonist nor-binaltorphimine 1.0 μmol, the effect of TRK-820 100 pmol on intrathecal morphine 0.3 nmol-induced scratching was tested. Total numbers of scratches after intrathecal injection were analyzed. After observing scratching behavior, sedation level was evaluated subjectively. Nociceptive threshold was determined by tail immersion test with intrathecal injections of the following agents: morphine (0.1-1.0 nmol), TRK-820 (10-100 pmol), morphine 0.1 nmol + TRK-820 10 pmol, and 5 μL of saline.Intrathecal TRK-820 dose-dependently inhibited intrathecal morphine-induced scratching compared with that in the saline group. Intraperitoneal nor-binaltorphimine completely inhibited the antiscratching effect of intrathecal TRK-820 100 pmol. The combination of morphine 0.3 nmol and TRK-820 did not alter the sedation score compared with that in the morphine 0.3 nmol group. Morphine 0.1 nmol + TRK-820 10 pmol significantly produced greater thermal antinociceptive effects than morphine 0.1 nmol.We demonstrated that intrathecal KOR agonists exert antipruritic effects on intrathecal morphine-induced itch without affecting sedation. The combination of intrathecal morphine and intrathecal KOR agonists produces more potent antinociceptive effects against a thermal stimulus compared with morphine alone.

Caffeic acid exhibits anti-pruritic effects by inhibition of multiple itch transmission pathways in mice

Itch is an unpleasant sensation that evokes a desire to scratch. Although often regarded as a trivial ‘alarming’ sensation, itch may be debilitating and exhausting, leading to reduction in quality of life. In the current study, the question of whether caffeic acid can be used to alleviate itch sensation induced by various pruritic agents, including histamine, chloroquine, SLIGRL-NH2, and β-alanine was investigated.It turned out that histamine-induced intracellular calcium increase was significantly blocked by caffeic acid in HEK293T cells that express H1R and TRPV1, molecules required for transmission of histamine-induced itch in sensory neurons. In addition, inhibition of histamine-induced intracellular calcium increase by caffeic acid was demonstrated in primary cultures of mouse dorsal root ganglion (DRG). When chloroquine, an anti-malaria agent known to induce histamine-independent itch – was used, it was also found that caffeic acid inhibits the induced response in both DRG and HEK293T cells that express MRGPRA3 and TRPA1, underlying molecular entities responsible for chloroquine-mediated itch. Likewise, intracellular calcium changes by SLIGRL-NH2 – an itch-inducing agent via PAR2 and MRGPRC11 – were decreased by caffeic acid as well. However, it was found that caffeic acid is not capable of inhibiting β-alanine-induced responses via its specific receptor MRGPRD. Finally, in vivo scratching behavior tests showed that caffeic acid indeed has anti-scratching effects against histamine, chloroquine, and SLIGRL-NH2 administration but not by β-alanine.Overall, the current study demonstrated that caffeic acid has anti-itch effects by inhibition of multiple itch mechanisms induced by histamine, chloroquine and SLIGRL-NH2.

Anti-pruritic activity of pioglitazone on serotonin-induced scratching in mice: Possible involvement of PPAR-gamma receptor and nitric oxide

Pioglitazone is a member of peroxisome proliferator-activated receptor gamma (PPARγ) agonists, particularly used in management of type II diabetes. However it also has effects in some dermatological disorders. The current study was designed to investigate the effects of oral administration of pioglitazone and the association of nitric oxide, in serotonin-induced scratching in mice. In order to produce the scratching activity, serotonin (141nm/site) was administered intradermally in the nape of the neck. Pioglitazone in concentrations of 10, 20, 40 and 80mg/kg, was peroral administered (p.o) as a single dose, 4h before the serotonin injection. PPAR-γ antagonist, GW9662 (2mg/kg, i.p); a non-specific nitric oxide synthase (NOS) inhibitor, NG-nitro-l-arginine methyl ester (l-NAME; 1mg/kg, i.p); or a nitric oxide precursor, l-arginine (100mg/kg, i.p.); adminstrated 15min before pioglitazone were analyzed for anti-scratching activity. Results obtained showed that pioglitazone (40 and 80mg/kg, p.o) reduced the scratching in a dose-dependent manner. GW9662 inverted the anti-scratching effect of pioglitazone (80mg/kg). Acute dose of l-NAME (1mg/kg, i.p) also prevented the anti-scratching property of pioglitazone (80mg/kg, p.o); although l-arginine was used in sub-effective dose (100mg/kg, i.p), however it potentiated the anti-scratching behavior when co-injected with pioglitazone (20mg/kg, p.o). The results indicate that acute pioglitazone has an anti-scratching effect on serotonin-induced scratching in mice. It is concluded that anti-scratching outcome of acute pioglitazone is initiated via activation of PPAR-γ receptor and to some extent by the NO pathway.

Effects of Atypical κ-Opioid Receptor Agonists on Intrathecal Morphine-Induced Itch and Analgesia in Primates

Itch/pruritus is the most common side effect associated with spinal administration of morphine given to humans for analgesia. The aim of this study was to investigate the effectiveness of kappa-opioid receptor (KOR) agonists with diverse chemical structures as antipruritics and to elucidate the receptor mechanism underlying the antipruritic effect in monkeys. In particular, previously proposed non-KOR-1 agonists, including nalfurafine [TRK-820, 17-cyclopropylmethyl-3,14 beta-dihydroxy-4,5 alpha-epoxy-6 beta-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan], bremazocine [(+/-)-6-ethyl-1,2,3,4,5,6-hexahydro-3-[(1-hydroxycyclopropy)-methyl]-11,11-dimethyl-2,6-methano-3-benzazocin-8-ol], and GR 89696 [4-[(3,4-dichlorophenyl)acetyl]-3-(1-pyrrolidinylmethyl)-1-piperazinecarboxylic acid methyl ester] were studied in various behavioral assays for measuring itch/scratching, analgesia, and respiratory depression. Systemic administration of nalfurafine (0.1-1 microg/kg), bremazocine (0.1-1 microg/kg), or GR 89696 (0.01-0.1 microg/kg) dose-dependently attenuated intrathecal morphine (0.03 mg)-induced scratching responses without affecting morphine antinociception. The combination of intrathecal morphine with these KOR agonists did not cause sedation. In addition, pretreatment with effective antiscratching doses of nalfurafine, bremazocine, or GR 89696 did not antagonize systemic morphine-induced antinociception and respiratory depression. The dose-addition analysis revealed that there is no subadditivity for nalfurafine in combination with morphine in the antinociceptive effect. Furthermore, the KOR antagonist study revealed that antiscratching effects of both nalfurafine and a prototypical KOR-1 agonist, U-50488H [trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cyclohexyl)-benzeneacetamide], could be blocked completely by a selective KOR antagonist, nor-binaltorphimine (3 mg/kg). These findings suggest that the agonist action on KOR mainly contributes to the effectiveness of these atypical KOR agonists as antipruritics, and there is no evidence for KOR subtypes or mu-opioid antagonist action underlying the effects of these KOR agonists. This mechanism-based study further supports the clinical potential of KOR agonists as antipruritics under the context of spinal opioid analgesia.