beta-endorphin and Pruritus

Pruritus is identified as an adverse drug reaction to arsenic trioxide, but the association of arsenic exposure with pruritus has not been investigated.. A cross-sectional study was conducted in Shimen, China. A Mendelian randomization analysis was conducted to confirm the causal relationship between genetically predicted percentages of monomethylated arsenic (MMA%) and dimethylated arsenic (DMA%) in urine with chronic pruritus in UK Biobank. A case-control study was then conducted to determine the biomarker for pruritus. Arsenite-treated mice were used to confirm the biomarker, and von Frey test was used to induce scratching bouts. Last, a randomized, double-blind, placebo-controlled trial was conducted to test the efficacy of naloxone in arsenic-exposed patients with pruritus in Shimen.. Hair arsenic (μg/g) showed a dose-response relationship with the intensity of itch in 1079 participants, with odds ratios (OR) of 1.11 for moderate-to-severe itch (p = 0.012). The Mendelian randomization analysis confirmed the causal relationship, with ORs of 1.043 for MMA% (p = 0.029) and 0.904 for DMA% (p = 0.077) above versus under median. Serum β-endorphin was identified as a significant biomarker for the intensity of itch (p < 0.001). Consistently, treatment with arsenite upregulated the level of β-endorphin (p = 0.002) and induced scratching bouts (p < 0.001) in mice. The randomized controlled trial in 126 participants showed that treatment with sublingual naloxone significantly relieved the intensity of itch in arsenic-exposed participants in 2 weeks (β = -0.98, p = 0.04).. Arsenic exposure is associated with pruritus, and β-endorphin serves as a biomarker of pruritus. Naloxone relieves pruritus in patients with arseniasis.

Topics: Animals; Arsenic; Arsenites; beta-Endorphin; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Humans; Mendelian Randomization Analysis; Mice; Naloxone; Pruritus

Most dialysis patients develop pruritus, for which current treatment is unsatisfactory. Endogenous opioids may be involved in this pruritus. We studied the effect of the opioid antagonist naltrexone on the pruritus of haemodialysis patients.. Naltrexone 50 mg per day by mouth was given to 15 haemodialysis patients with severe resistant pruritus in a randomised, double-blind, placebo-controlled crossover trial. The naltrexone or placebo periods lasted 7 days each with a 7-day washout between the two periods. Pruritus was assessed by the patients on a visual analogue scale from 0 (no pruritus) to 10 (maximum), and mean daily scores were calculated. Plasma histamine and beta-endorphin levels were measured, and spontaneous and stimulated basophil histamine-release were determined.. The median pruritus scores at the end of the naltrexone treatment were 2.1 (interquartile range 1.5-2.15) for the naltrexone-placebo sequence and 1.0 (0.4-1.15) for the placebo-naltrexone sequence. The respective values before naltrexone was given were 9.9 (9.85-9.95) and 9.9 (9.3-10.0). Plasma beta-endorphin levels were normal and remained unchanged during the study. Plasma histamine levels were high (mean 2.32 [SD 0.11] ng/mL, normal < 1.0) and decreased after naltrexone (to 1.8 [0.09], p < 0.01). Basophils from haemodialysis patients stimulated by interleukin-3 plus IgE antibodies released high amounts of histamine. The increase was 78.3 (19.3)% compared with 26.6 (16.3)% for five normal controls (p < 0.01). Incubation of the basophils with naloxone, another opioid antagonist, prevented this effect.. Our data suggest short-term efficacy with few side-effects for the amelioration of uraemic pruritus with naltrexone.

Topics: beta-Endorphin; Cross-Over Studies; Double-Blind Method; Histamine; Humans; Naltrexone; Narcotic Antagonists; Pruritus; Renal Dialysis; Uremia

 This study investigated the sex differences of the inflammatory mediator level at the time of itch onset in patients with chronic venous disease (CVD). Twenty-seven CVD patients (nineteen women, eight men) and nine healthy controls (five women, four men) participated. CVD-associated itching was observed in both men and women. Before sclerotherapy, both sexes had elevations in several itch-related mediators. Among these, women had significantly higher tryptase, whereas men had significantly higher β-endorphin and adrenocorticotropic hormone. After sclerotherapy, all levels normalized in both sexes. In this study, itching was increased tryptase in women and increased adrenocorticotropic hormone and β-endorphin in men.

Topics: Adrenocorticotropic Hormone; Adult; Aged; beta-Endorphin; Chronic Disease; Female; Humans; Inflammation Mediators; Male; Middle Aged; Pruritus; Sclerotherapy; Sex Characteristics; Tryptases; Vascular Diseases

How neuropeptides in the primate spinal cord regulate itch and pain is largely unknown. Here we elucidate the sensory functions of spinal opioid-related peptides and gastrin-releasing peptide (GRP) in awake, behaving monkeys. Following intrathecal administration, β-endorphin (10-100 nmol) and GRP (1-10 nmol) dose-dependently elicit the same degree of robust itch scratching, which can be inhibited by mu-opioid peptide (MOP) receptor and GRP receptor (BB2) antagonists, respectively. Unlike β-endorphin, which produces itch and attenuates inflammatory pain, GRP only elicits itch without affecting pain. In contrast, enkephalins (100-1000 nmol) and nociceptin-orphanin FQ (3-30 nmol) only inhibit pain without eliciting itch. More intriguingly, dynorphin A(1-17) (10-100 nmol) dose-dependently attenuates both β-endorphin- and GRP-elicited robust scratching without affecting pain processing. The anti-itch effects of dynorphin A can be reversed by a kappa-opioid peptide (KOP) receptor antagonist nor-binaltorphimine. These nonhuman primate behavioral models with spinal delivery of ligands advance our understanding of distinct functions of neuropeptides for modulating itch and pain. In particular, we demonstrate causal links for itch-eliciting effects by β-endorphin-MOP receptor and GRP-BB2 receptor systems and itch-inhibiting effects by the dynorphin A-KOP receptor system. These studies will facilitate transforming discoveries of novel ligand-receptor systems into future therapies as antipruritics and/or analgesics in humans.

Topics: Analgesics, Opioid; Animals; Behavior, Animal; beta-Endorphin; Dynorphins; Female; Gastrin-Releasing Peptide; Hyperalgesia; Injections, Spinal; Macaca mulatta; Male; Neuropeptides; Pain; Pruritus; Spinal Cord

To identify the effect of beta-endorphin in the development of paresthesia in hypertrophic scar by detecting the expression and content of beta-endorphin in human normal skin and hypertrophic scar.. Hypertrophic scar samples were collected from 42 patients with hypertrophic scar for 1-20 years (mean, 4.5 years), including 15 males and 27 females with an average age of 32.6 years (range, 16-50 years). According to the kind of paresthesia, they were divided into 3 gourps: non-pain-pruritus group (n=20), pruritus group (n=14), and pain-pruritus group (n=8). Normal skin samples (normal skin group) were harvested from 5 patients undergoing skin grafting surgery, including 3 males and 2 females with an average age of 24.6 years (range, 15-37 years). The immunofluorescence method was used to observe the expression of beta-endorphin and ELISA method to detect the concentrations of beta-endorphin in the tissues.. The beta-endorphin expressed in all samples, and it expressed around peripheral nerve fibers in the dermis, fibroblasts, and monocytoid cells principally; and it expressed significantly stronger in pruritus group and pain-pruritus group than in non-pain-pruritus group and normal skin group. The beta-endorphin content was (617.401 +/- 97.518) pg/mL in non-pain-pruritus group, (739.543 +/- 94.149) pg/mL in pruritus group, (623.294 +/- 149.613) pg/mL in pain-pruritus group, and (319.734 +/- 85.301) pg/mL in normal skin group; it was significantly higher in non-pain-pruritus group, pruritus group, and pain-pruritus group than in normal skin group (P < 0.05); it was significantly higher in pruritus group than in non-pain-pruritus group and pain-pruritus group (P < 0.05); and there was no significant difference between non-pain-pruritus group and pain-pruritus group (P > 0.05).. The expression of beta-endorphin is high in hypertrophic scar, it may play an important role in process of pruritus in these patients.

Topics: Adolescent; Adult; beta-Endorphin; Case-Control Studies; Cicatrix, Hypertrophic; Enzyme-Linked Immunosorbent Assay; Female; Fibroblasts; Humans; Male; Middle Aged; Pruritus; Skin; Young Adult

Psoriasis is a complex, multifactorial inflammatory skin disease with genetic and environmental interactions. Patients with psoriasis exhibit erythematous plaques with itch, but the mechanisms of psoriatic itch are poorly understood.. This study was performed to investigate epidermal nerve density and opioid receptor levels in psoriatic skin with or without itch.. Twenty-four patients with psoriasis aged between 39 and 82 years were included in this study. The number of epidermal nerve fibres, the levels of semaphorin 3A (Sema3A) and the expression patterns of μ- and κ-opioid systems were examined immunohistologically in skin biopsies from psoriatic patients with or without itch and healthy volunteers as controls.. The number of epidermal nerve fibres tended to increase in approximately 40% of psoriatic patients with itch compared with healthy controls, while such intraepidermal nerves were not observed in other itchy patients. In comparison with healthy controls, Sema3A levels also tended to decrease in the epidermis of psoriatic patients with itch. However, no relationship was found between nerve density and Sema3A levels in the epidermis of psoriatic patients with itch. The levels of μ-opioid receptor and β-endorphin in the epidermis were the same in healthy controls and psoriatic patients with or without itch. The levels of κ-opioid receptor and dynorphin A were significantly decreased in the epidermis of psoriatic patients with itch compared with healthy controls.. Based on Sema3A levels in the epidermis, epidermal opioid systems, rather than hyperinnervation, may be involved in the pathogenesis of psoriatic itch.

Topics: Adult; Aged; beta-Endorphin; Biopsy, Needle; Case-Control Studies; Dynorphins; Epidermis; Female; Humans; Immunohistochemistry; Male; Middle Aged; Nerve Fibers; Pruritus; Psoriasis; Receptors, Opioid; Semaphorin-3A

Although itch is the predominant symptom of atopic dermatitis (AD), it is poorly characterized and subjective. The objective assessment of itch intensity is important for treatment and follow-up in patients with AD.. To determine what objective clinical parameter(s) could be used as biomarker(s) for itch intensity in patients with AD.. This is a retrospective and cross-sectional study. Seventy-five patients, aged 7 months-49 years with equal sex ratio, were enrolled in 2000 according to criteria proposed by Hanifin and Rajka. Thirty-five age- and sex-matched subjects who visited the dermatological clinic but were otherwise healthy served as controls. Subjective itch intensity was divided into four grades of severity. Disease severity was measured by SCORAD index, which also includes itch intensity as part of the measurement. Transepidermal water loss (TEWL) and skin surface pH were measured by noninvasive methods in clinically normal skin on the forearm. Serum beta-endorphin and vasoactive intestinal peptide (VIP) were determined by radioimmunoassay. Ordinal logistic regression was used to assess the trend of the subjective itch intensity and SCORAD index by serum IgE, beta-endorphin, VIP, TEWL and skin pH.. There were significant trends for itch intensity with IgE, beta-endorphin and TEWL. After adjustment for sex, age and other variables, the odds ratio (OR) for itch intensity by log IgE, beta-endorphin and TEWL was 2.103 [95% confidence interval (CI) 1.222-3.618], 1.100 (95% CI 1.005-1.203) and 1.081 (95% CI 1.009-1.158), respectively. The OR for disease severity by log IgE, beta-endorphin and TEWL was 2.250 (95% CI 1.149-4.407), 1.156 (95% CI 1.086-1.231) and 1.071 (95% CI 0.971-1.182), respectively. In contrast, there was no association between serum VIP concentration and itch intensity.. Beta-endorphin and IgE are both useful biomarkers for itch and disease severity in patients with AD, while TEWL is a good biomarker for itch intensity. These biomarkers provide a way to assess the itch intensity in patients with AD.

Topics: Adolescent; Adult; beta-Endorphin; Biomarkers; Child; Child, Preschool; Dermatitis, Atopic; Epidemiologic Methods; Female; Humans; Hydrogen-Ion Concentration; Immunoglobulin E; Infant; Male; Middle Aged; Pruritus; Severity of Illness Index; Vasoactive Intestinal Peptide; Water Loss, Insensible

Topics: beta-Endorphin; Humans; Pruritus; Renal Dialysis; Uremia

Atopic dermatitis (AD) is a pruritic cutaneous inflammatory condition. As pruritus and pain are very close symptoms, we determined the beta-endorphin serum concentrations in 21 atopic children with pruritus (group A) and 20 children with healed AD without pruritus (group B). Twenty-five healthy school children were the control group. The beta-endorphin serum concentrations (14.95 +/- 2.75 pmol/l) in group A were statistically (P < 0.001) elevated in our patients compared to controls (8.85 +/- 2.39 pmol/l) whereas these in group B were not elevated (9.4 +/- 2.46 pmol/l). We suggest that the elevated beta-endorphin concentrations in atopic patients with pruritus confirm the hypothesis that there is an increased activity of their opioid system and that an opioid antagonist might block itching which is their major clinical symptom.

Topics: beta-Endorphin; Child; Child, Preschool; Dermatitis, Atopic; Female; Humans; Male; Pruritus

The effect of various opioid or putative neurotransmitter peptides on histamine-induced itch and flare responses was studied in humans after intradermal injection. Significant enhancement of the histamine responses was induced by the stable methionine-enkephalin analogue FK 33-824, beta-endorphin and morphine. The putative neurotransmitters substance P and vasoactive intestinal polypeptide (VIP)--which moreover are potent histamine liberators--had no enhancing effect. The potentiation induced by FK 33-824 was induced neither by local pretreatment with Compound 48/80 to deplete the local stores of mast-cell-bound histamine, nor by oral pretreatment with indomethacin to inhibit prostaglandin formation in the skin. Thus, the enhancement did not seem to be due to histamine release or to prostaglandin formation and the mechanism of the effect remains to be shown. The specific morphine antagonist naloxone did not inhibit the potentiation by FK 33-824, which might indicate that ordinary opiate receptors were not involved. The results support the idea that pain and itch are qualitatively separate processes and suggest possible mechanisms of morphine-induced pruritus. The findings are of particular interest in view of recent reports on the presence of methionine-enkephalin in Merkel cells.

Topics: Adolescent; Adult; beta-Endorphin; D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; Dinoprostone; Drug Synergism; Endorphins; Enkephalin, Methionine; Female; Histamine; Humans; Indomethacin; Male; Middle Aged; Morphine; Naloxone; Prostaglandins E; Pruritus; Skin; Substance P; Vasoactive Intestinal Peptide