Abstract:Chronic stress is widely considered to trigger or enhance itch, especially for pruritic dermatitis. However, the molecular mechanisms linking chronic stress and itch are still unknown. The present study aimed to elucidate the role of adrenergic signaling in itch hypersensitivity following heterotypic chronic intermittent stress (HIS) in rats. HIS significantly increased hindlimb scratching, but not forepaw swiping, induced by intradermal injection of 5-hydroxytryptamine (5-HT) in the rat cheek. Coadministratio… Show more
“…As described previously646566, we intradermally injected chemicals into the cheek of rats. Rats were shaved on cheeks (approx.…”
Section: Methodsmentioning
confidence: 99%
“…As previously described4366, tail immersion test was employed to determine heat pain sensitivity in rats. Briefly, the terminal 3 cm of a rat’s tail was immersed in hot water bath at 52 °C and the latency of tail flick was recorded with a cutoff time of 15 seconds to avoid tissue damage.…”
Section: Methodsmentioning
confidence: 99%
“…To test mechanical hypersensitivity, we determined the mechanical sensitivity of hind paws by using series of von Frey filaments (4 g, 15 g, and 26 g) as previous report66. Rats were placed on a metal mesh floor and von Frey filaments were applied from underneath the floor.…”
Although 5-HT has been implicated in cholestatic itch and antinociception, two common phenomena in patients with cholestatic disease, the roles of 5-HT receptor subtypes are unclear. Herein, we investigated the roles of 5-HT receptors in itch and antinociception associated with cholestasis, which was induced by common bile duct ligation (BDL) in rats. 5-HT-induced enhanced scratching and antinociception to mechanical and heat stimuli were demonstrated in BDL rats. 5-HT level in the skin and spinal cord was significantly increased in BDL rats. Quantitative RT-PCR analysis showed 5-HT1B, 5-HT1D, 5-HT2A, 5-HT3A, 5-HT5B, 5-HT6, and 5-HT7 were up-regulated in peripheral nervous system and 5-HT1A, 5-HT1F, 5-HT2B, and 5-HT3A were down-regulated in the spinal cord of BDL rats. Intradermal 5-HT2, 5-HT3, and 5-HT7 receptor agonists induced scratching in BDL rats, whereas 5-HT3 agonist did not induce scratching in sham rats. 5-HT1A, 5-HT2, 5-HT3, and 5-HT7 agonists or antagonists suppressed itch in BDL rats. 5-HT1A agonist attenuated, but 5-HT1A antagonist enhanced antinociception in BDL rats. 5-HT2 and 5-HT3 agonists or antagonists attenuated antinociception in BDL rats. Our data suggested peripheral and central 5-HT system dynamically participated in itch and antinociception under cholestasis condition and targeting 5-HT receptors may be an effective treatment for cholestatic itch.
“…As described previously646566, we intradermally injected chemicals into the cheek of rats. Rats were shaved on cheeks (approx.…”
Section: Methodsmentioning
confidence: 99%
“…As previously described4366, tail immersion test was employed to determine heat pain sensitivity in rats. Briefly, the terminal 3 cm of a rat’s tail was immersed in hot water bath at 52 °C and the latency of tail flick was recorded with a cutoff time of 15 seconds to avoid tissue damage.…”
Section: Methodsmentioning
confidence: 99%
“…To test mechanical hypersensitivity, we determined the mechanical sensitivity of hind paws by using series of von Frey filaments (4 g, 15 g, and 26 g) as previous report66. Rats were placed on a metal mesh floor and von Frey filaments were applied from underneath the floor.…”
Although 5-HT has been implicated in cholestatic itch and antinociception, two common phenomena in patients with cholestatic disease, the roles of 5-HT receptor subtypes are unclear. Herein, we investigated the roles of 5-HT receptors in itch and antinociception associated with cholestasis, which was induced by common bile duct ligation (BDL) in rats. 5-HT-induced enhanced scratching and antinociception to mechanical and heat stimuli were demonstrated in BDL rats. 5-HT level in the skin and spinal cord was significantly increased in BDL rats. Quantitative RT-PCR analysis showed 5-HT1B, 5-HT1D, 5-HT2A, 5-HT3A, 5-HT5B, 5-HT6, and 5-HT7 were up-regulated in peripheral nervous system and 5-HT1A, 5-HT1F, 5-HT2B, and 5-HT3A were down-regulated in the spinal cord of BDL rats. Intradermal 5-HT2, 5-HT3, and 5-HT7 receptor agonists induced scratching in BDL rats, whereas 5-HT3 agonist did not induce scratching in sham rats. 5-HT1A, 5-HT2, 5-HT3, and 5-HT7 agonists or antagonists suppressed itch in BDL rats. 5-HT1A agonist attenuated, but 5-HT1A antagonist enhanced antinociception in BDL rats. 5-HT2 and 5-HT3 agonists or antagonists attenuated antinociception in BDL rats. Our data suggested peripheral and central 5-HT system dynamically participated in itch and antinociception under cholestasis condition and targeting 5-HT receptors may be an effective treatment for cholestatic itch.
“…81 Atenolol was reported to be effective in treating IAP. 83 Propranolol's therapeutic effect in treating IAP may also be explained by its role as an antagonist for certain serotonin receptors. 82 Recently, researchers discovered that injection of 5-hydroxytryptamine (5-HT) can induce scratching in na€ ıve rats.…”
Many systemic medications have been used off-label in cutaneous diseases. Use of β-adrenergic-blocking agents has risen in popularity among dermatologists since the discovery of their efficacy in treating infantile haemangioma. There has also been an increase in the interest of the applications of β-blockers in other skin disorders. Overall, β-blockers are effective in treating diseases of vascular origin and promote wound healing. They are relatively safe and inexpensive medications that could be included in the armamentarium against skin diseases.
“…Peng et al. () found that chronic stress significantly enhances the scratching number when administrating 5‐HT into cheek skin in rats, and β 2 ‐adrenoceptors may mediate itch hypersensitivity via upregulating proinflammatory factors, such as TNF‐α in the skin. All the studies mentioned previously concentrated on the facilitative effects of chronic stress (depression) on itch hypersensitivity instead of the effects of chronic itch on depression.…”
BackgroundThe interactive aggravation of pruritus and depression is well‐known, but an appropriate experimental model that could mimic this behavioral phenomenon is still lacking. Thus, a systematic animal behavioral investigation was carried out in this study. This will promote the research and treatment of pruritus and depression.MethodsThe 2,4‐dinitrofluorobenzene (DNFB)‐induced chronic itch model was established to measure the depression index by forced swimming test (FST), tail suspension test (TST), and splash test (ST). The chronic unpredicted mild stress (CUMS)‐induced depression model was established to measure spontaneous itch and acute histamine or chloroquine‐induced itch behaviors. A depression and itch combining model was also established to measure the scratching and depression behaviors. The motor function of DNFB mice was analyzed by the rotarod test.ResultsThe scratching number, the immobility time in the FST and TST, and the grooming number in the ST test were all significantly increased in the chronic itch model. Mice receiving CUMS treatment showed significantly increased spontaneous scratching number, immobility time in the FST and TST tests, and grooming number in the ST. The combined model showed increased immobility time in FST and TST tests and increased grooming number in ST comparing to the depression model, and showed increased scratching number comparing to the chronic itch model. After histamine (His) or chloroquine (CQ) injection, the scratching numbers of CUMS mice were all significantly increased compared to those of His‐ and CQ‐control, respectively. Anti‐depression drug ketamine could significantly inhibit the depression‐like behaviors of CUMS mice, and simultaneously stopped the promoting effect on His‐induced acute itch.ConclusionsThis study established an appropriate cross aggravation experimental mode and demonstrated that there is cross aggravation between pruritus and depression. The illumination of related mechanisms underlying this cross aggravation effect will provide theoretical basis for the prevention and treatment of depression and pruritus.
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