Pruritus (itch sensation) is a significant clinical problem. The aim of this study was to elucidate the roles of opioid receptor types and the site of action in opioid-induced itch in monkeys. Observers who were blinded to the conditions counted scratching after administration of various drugs. Intravenous (i.v.) administration of opioid receptor (MOR) agonists (fentanyl, alfentanil, remifentanil, and morphine) evoked scratching in a doseand time-dependent manner. However, the opioid agonist

Pruritus (itch sensation) is the most common side effect associated with spinal administration of morphine given to humans for analgesia. A variety of agents have been proposed as antipruritics with poorly understood mechanisms and they are effective with variable success. kappa-Opioid agonists possess several actions that are opposite to micro -opioid agonists. We proposed to investigate the role of kappa-opioid receptors (KORs) in morphine-induced scratching and antinociception in monkeys. Scratching responses were counted by observers blinded to treatment. Antinociception was measured by a warm water (50 degrees C) tail-withdrawal assay. Pretreatment with low doses of trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cyclohexyl)-benzeneacetamide (U-50488H) (0.032-0.18 mg/kg s.c.), a selective KOR agonist, dose dependently suppressed the s.c. morphine dose-effect curve for scratching and potentiated s.c. morphine-induced antinociception. In addition, s.c. U-50488H attenuated i.t. morphine (10 and 32 micro g)-induced scratching while maintaining or enhancing i.t. morphine-induced antinociception. The combination of s.c. or i.t. morphine with low doses of U-50488H did not cause sedation. More importantly, pretreatment with 3.2 mg/kg nor-binaltorphimine, a selective KOR antagonist, blocked the effects of s.c. U-50488H on both s.c. and i.t. morphine-induced scratching. These results indicate that activation of KOR attenuates morphine-induced scratching without interfering with antinociception in monkeys. This mechanism-based finding provides functional evidence in support of the clinical potential of KOR agonists as antipruritics in the presence of MOR agonist-induced pruritus.

Objective To determine whether biennial eye evaluation or telemedicine screening are cost-effective alternatives to current recommendations for the estimated 10 million people aged 30 to 84 with diabetes but no or minimal diabetic retinopathy. Data Sources United Kingdom Prospective Diabetes Study, National Health and Nutrition Examination Survey, American Academy of Ophthalmology Preferred Practice Patterns, Medicare Payment Schedule. Study Design Cost-effectiveness Monte Carlo simulation. Data Collection/Extraction Methods Literature review, analysis of existing surveys. Principal Findings Biennial eye evaluation was the most cost-effective treatment option when the ability to detect other eye conditions was included in the model. Telemedicine was most cost-effective when other eye conditions were not considered or when telemedicine was assumed to detect refractive error. The current annual eye evaluation recommendation was costly compared to either treatment alternative. Self-referral was most cost-effective up to a willingness to pay (WTP) of $37,600, with either biennial or annual evaluation most cost-effective at higher WTP levels. Conclusions Annual eye evaluations are costly and add little benefit compared to either plausible alternative. More research on the ability of telemedicine to detect other eye conditions is needed to determine whether it is more cost-effective than biennial eye evaluation.

and 4 Oxford Natural Products, Charlbury, Oxfordshire 1 Orphanin FQ (OFQ), an endogenous peptide for ORL1 receptors, has been identi®ed. Although the actions of OFQ have much in common with those of opioid peptides at the cellular level, behavioral studies in rodents seem con¯icting. 2 The aim of this study was to investigate the potential pronociceptive or antinociceptive function of peripheral ORL1 receptors in primates. Experiments were conducted to verify whether local administration of OFQ can attenuate capsaicin-induced nociception and whether peripheral ORL1 receptors selectively mediate the local action of OFQ in monkeys. 3 Capsaicin (100 mg) was administered subcutaneously in the tail to locally evoke a nociceptive response (thermal allodynia/hyperalgesia), which was manifested as a reduced tail-withdrawal latency in normally innocuous 468C warm water. 4 Co-administration of OFQ (1 ± 30 mg) with capsaicin in the tail dose-dependently inhibited thermal nociception. However, a locally eective dose of OFQ (30 mg), when applied in the back, did not inhibit capsaicin-induced nociception. 5 OFQ-induced local antinociception was antagonized by a small dose (10 mg) of J-113397, a selective ORL1 receptor antagonist, in the tail. Similarly, s.c. administration of 10 mg of J-113397 in the back did not antagonize local antinociception of OFQ. 6 In addition, s.c. administration of either OFQ or J-113397 in the tail alone did not change its thermal nociceptive threshold. Local administration of opioid receptor antagonists selective for mu, kappa, and delta opioid receptors did not antagonize OFQ-induced local antinociception. Local administration of J-113397 also did not interfere with the local actions of mu, kappa, and delta opioid agonists in the tail. 7 These results provide the ®rst functional evidence that activation of peripheral ORL1 receptors produces thermal antinociception in primates and this action is independent of antinociception produced at classical opioid receptors. British Journal of Pharmacology (2002) 135, 943 ± 950

Background-To estimate the incremental cost-effectiveness of amblyopia screening at preschool and kindergarten, we compared the costs and benefits of 3 amblyopia screening scenarios to no screening and to each other: (1) acuity/stereopsis (A/S) screening at kindergarten, (2) A/S screening at preschool and kindergarten, and (3) photoscreening at preschool and A/S screening at kindergarten.