Effect of intravenous alizapride on spinal morphine-induced pruritus.
(25/125)
BACKGROUND: This double-blind study was undertaken to determine whether alizapride inhibits spinal morphine-induced pruritus. METHODS: Eighty-four patients undergoing Caesarean section under spinal anaesthesia (100 mg of hyperbaric lidocaine 5% plus morphine 0.2 mg) were randomly allocated to one of two groups. Just after birth, alizapride-50 mg (alizapride group) or metoclopramide-10 mg (metoclopramide group) were injected i.v. Patients were assessed after surgery for pruritus (absent, mild, moderate or severe) or other untoward symptoms. RESULTS: In the metoclopramide group, pruritus was absent in 5 (12%) patients, mild in 23 (55%), moderate in 11 (26%), and severe in 3 (7%), while in the alizapride group, these incidences were, respectively, 5 (12%), 33 (79%), 4 (10%), and 0 (P=0.045, chi(2)-test). There was no difference in the incidence of side-effects, which were all minor. CONCLUSIONS: Alizapride reduced the severity of morphine-induced pruritus. (+info)
Capsaicin and menthol in the treatment of itch and pain: recently cloned receptors provide the key.
(26/125)
Topical capsaicin is reported to be an effective treatment for idiopathic intractable pruritus ani. While both capsaicin and menthol application produce a transient perianal burning sensation, only capsaicin relieves itching. Classical observations on functional desensitisation of nociceptors by capsaicin may explain the beneficial effects but the recent discovery of a range of receptors which respond to capsaicin, menthol, and temperature, and their expression in subsets of sensory nerve fibres, provides an exciting prospect towards advancing our understanding and treatment of sensory dysfunction. (+info)
Topical capsaicin--a novel and effective treatment for idiopathic intractable pruritus ani: a randomised, placebo controlled, crossover study.
(27/125)
PURPOSE: Pruritus ani is a common and embarrassing proctological condition which can be very difficult to treat. We report the results of a double blind placebo controlled study of treatment with capsaicin. METHODS: Firstly, a pilot open study was carried out on five patients to establish which of two doses was the most acceptable by comparing effectiveness and side effects. Secondly, a double blind, placebo controlled, crossover study of topical capsaicin was performed. This study involved two four week treatment phases separated by a one week washout phase. Forty four patients were randomised to receive locally either active capsaicin (0.006%) or placebo (menthol 1%) ointment over a four week period (22 patients per group). After four weeks of treatment and a one week washout period, the placebo group began to receive capsaicin while the treated group received placebo (menthol 1%) for another four weeks. At the end of the controlled study, responders from both groups continued with capsaicin treatment in an open labelled manner. RESULTS: Thirty one of 44 patients experienced relief during capsaicin treatment periods and did not respond to menthol; all patients not responding to capsaicin also failed on menthol (p<0.0001). In 13 patients, treatment with capsaicin was unsuccessful: eight patients did not respond to capsaicin treatment, one responded equally to capsaicin and placebo, and four others dropped out because of side effects. During the follow up period (mean 10.9 (SD 5.8) months), 29 "responders" needed a mean application of capsaicin every day (1.6 (SD 1.2); range 0.5-7 days) to remain symptom free (or nearly symptom free). CONCLUSION: Capsaicin is a new, safe, and highly effective treatment for severe intractable idiopathic pruritus ani. (+info)
Characterization of scratching responses in rats following centrally administered morphine or bombesin.
(28/125)
The aim of this study was to characterize scratching behavior elicited by central administration of morphine or bombesin in rats, and to determine the role of opioid receptors in scratching induced by both pruritogenic agents. Central administration included intracisternal (i.c.), intrathecal (i.t.), and intracerebroventricular (i.c.v.) routes. Scratching events made with hind paws were counted by observers blinded to treatment conditions. Intracisternal morphine (0.01-0.1 microg) produced dose-dependent increases in scratching; the maximum response to i.c. morphine 0.1 microg was approximately 500 scratches within a 1-hour period. Neither i.t. nor i.c.v. morphine significantly increased scratching. Bombesin (0.01-0.32 microg) elicited robust scratching following i.c. administration. The maximum response to i.c. bombesin 0.32 microg was approximately 4000 scratches within a 1-hour period. Both i.t. and i.c.v. bombesin produced profound scratching at similar doses. Antagonist studies confirmed that mu-opioid receptors selectively mediate i.c. morphine-induced scratching. However, selective mu-, kappa-, and delta-opioid antagonists did not attenuate i.c. bombesin-induced scratching. These results demonstrate that morphine and bombesin elicit scratching through different receptor mechanisms, at different central sites, and to different degrees. (+info)
Topical menthol--a human model for cold pain by activation and sensitization of C nociceptors.
(29/125)
Although cold hyperalgesia is a frequent symptom in patients with neuropathic pain, it is poorly understood. We investigated the mechanisms of cold pain by studying the effect of menthol on pain, temperature perception, touch sensation and skin perfusion. In 10 subjects, 40% l-menthol, and ethanol, serving as control, were topically applied to the forearm in a double-blinded two-way crossover study. Menthol induced significant pain and cold sensations, punctate and cold hyperalgesia and an increase in cutaneous perfusion. Other mechano-sensory and thermal tests were unchanged (touch, cold and warm detection thresholds, heat pain threshold; no dynamic and static hyperalgesia, no wind-up). To investigate the underlying mechanisms, the effects of menthol versus ethanol on the dorsum of the hand were tested during A fibre conduction blockade of the superficial radial nerve in another 10 subjects. The block itself led to hypoaesthesia for mechanical stimuli and anaesthesia for cold perception, but induced an increase in cold-mediated pain. This was due to lack of inhibition of C nociceptors normally exerted by concomitant activation of A fibres. Under these conditions, menthol-induced cold sensation and punctate hyperalgesia were abolished. However, menthol induced spontaneous pain with a trend to higher values than without block. Furthermore, the hyperalgesia to cold stimuli, that was already present during A fibre block, was further increased significantly by menthol. We suggested that menthol acts to sensitize cold-sensitive peripheral vasoactive C nociceptors and activates cold-specific A delta fibres. Punctate hyperalgesia is due to central sensitization based on the ongoing activity in the sensitized cold-sensitive peripheral C nociceptors. In conclusion, topical menthol is a human model for cold pain by exposing for the first time the mechanism of sensitized peripheral cold C nociceptors that may also be involved in neuropathic pain. (+info)
Smoking mentholated cigarettes has been suggested to convey a greater cancer risk compared with smoking nonmentholated cigarettes. Two of the possible mechanisms by which mentholated cigarette smoking could increase risk are by increasing systemic exposure to tobacco smoke toxins and by affecting the metabolism of nicotine or tobacco smoke carcinogens. To examine these possibilities, we performed a crossover study in 14 healthy smokers, one-half of whom were African-Americans and one-half whites. Subjects were randomly assigned to smoke mentholated or nonmentholated cigarettes for 1 week, then to cross over to the other type of cigarettes for another week. Subjects were confined to a Clinical Research Center for 3 days of each week, during which time blood levels of nicotine and carbon monoxide were measured throughout the day and an intravenous infusion of deuterium-labeled nicotine and cotinine was administered to determine the rate and pathways of nicotine metabolism. The systemic intake of nicotine and carbon monoxide was, on average, not affected by mentholation of cigarettes. Mentholated cigarette smoking did significantly inhibit the metabolism of nicotine (clearance: 1289 versus 1431 ml/min, two sided, p = 0.02). Inhibition of nicotine metabolism occurred both by slower oxidative metabolism to cotinine and by slower glucuronide conjugation. Our data do not support the hypothesis that mentholated cigarette smoking results in a greater absorption of tobacco smoke toxins. Our finding of impaired metabolism of nicotine while mentholated cigarette smoking suggests that mentholated cigarette smoking enhances systemic nicotine exposure. (+info)
Idiopathic perianal pruritus: washing compared with topical corticosteroids.
(31/125)
BACKGROUND: Idiopathic perianal pruritus is a poorly managed condition. Topical corticosteroids are effective in idiopathic perianal pruritus, but they may cause some side effects. In this study, the effectiveness of topical steroids were compared with perianal cleansers in the treatment of idiopathic perianal pruritus. PATIENTS AND METHODS: Seventy two patients with the complaint of perianal pruritus were evaluated; 60 of the 72 patients were found to be idiopathic. Twenty eight patients were treated with topical steroids and 32 patients were treated only with a liquid cleanser. RESULTS: At the end of this two week period, cleansers were found to be as effective as topical corticosteroids. CONCLUSION: This study shows that perianal cleansers can be used as a safe first step treatment in idiopathic perianal pruritus. (+info)
Comparison of pharmacological activities of three distinct kappa ligands (Salvinorin A, TRK-820 and 3FLB) on kappa opioid receptors in vitro and their antipruritic and antinociceptive activities in vivo.
(32/125)
Salvinorin A, TRK-820 (17-cyclopropylmethyl-3,14beta-dihydroxy-4,5alpha-epoxy-6beta-[N-methyl-trans-3-( 3-furyl) acrylamido]morphinan hydrochloride), and 3FLB (diethyl 2,4-di-[3-fluorophenyl]-3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonane-9-one-1,5-dica rboxylate) are structurally distinctly different from U50,488H [(trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide methanesulfonate], the prototypic selective kappa agonist. Here, we investigated their in vitro pharmacological activities on receptors expressed in Chinese hamster ovary cells and in vivo antiscratch and antinociceptive activities in mice. All three compounds showed high selectivity for the kappa opioid receptor (KOR) over the mu opioid receptor (MOR) and delta opioid receptor (DOR) and nociceptin or orphanin FQ receptors. In the guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding assay, all three were full agonists on the KOR. The rank order of affinity and potency for the KOR was TRK-820 >> U50,488H approximately salvinorin A >> 3FLB. TRK-820 acted as a partial agonist on MOR and DOR, whereas salvinorin A and 3FLB showed no activities on these receptors. Salvinorin A, TRK-820, and 3FLB caused internalization of the human KOR in a dose-dependent manner. Interestingly, although salvinorin A and U50,488H had similar potencies in stimulating [(35)S]GTPgammaS binding, salvinorin A was about 40-fold less potent than U50,488H in promoting internalization. Following 4-h incubation, all three compounds induced down-regulation of the human KOR, with salvinorin A causing a lower extent of down-regulation. Although TRK-820 was potent and efficacious against compound 48/80-induced scratching, salvinorin A showed low and inconsistent effects, and 3FLB was inactive. In addition, salvinorin A and 3FLB were not active in the acetic acid abdominal constriction test. The discrepancy between in vitro and in vivo results may be due to in vivo metabolism of salvinorin A and 3FLB and possibly to their effects on other pharmacological targets. (+info)