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Buprenorphine is a mixed opioid receptor agonist-antagonist. Recently, buprenorphine was reported to act as an agonist to opioid receptor like-1 (ORL1) receptor. In the present study, we examined the role of spinal and supraspinal receptors and spinal and supraspinal ORL1 receptors in producing an analgesic effect by intrathecal (i.t.), intracerebroventricular (i.c.v.), or i.p. administration of buprenorphine in the rat formalin test. Male rats were prepared with i.t. catheters or i.c.v. injection cannulas. The paw formalin injection (50 l of 5% formalin) induces biphasic flinching (phase 1, 0 -6 min; phase 2, 10 -60 min) of the injected paw. Buprenorphine, naloxone (a -opioid Buprenorphine is a derivative of the morphine alkaloid thebaine and is used for the treatment of moderate to severe pain (Johnson et al., 2005). Buprenorphine has been reported to have high affinities for -, -, and ␦-opioid receptors with K i values in the nanomolar range. (Huang et al., 2001).Recently, buprenorphine has been reported to act as an agonist at opioid receptor like-1 (ORL1) receptors (BlomsFunke et al., 2000). Lutfy et al. (2003) reported that the antinociceptive effect of subcutaneously administered buprenorphine was markedly enhanced in mice lacking ORL1 receptors in the tail-flick test and that systemic administration of an ORL1 receptor antagonist enhanced the analgesic effect of s.c. administered buprenorphine. Mice lacking -opioid receptors failed to exhibit an antinociceptive effect after s.c. administration of buprenorphine (Lutfy et al., 2003).Moreover, buprenorphine did not produce an analgesic effect in 1 -opioid receptor-deficient mice (Kamei et al., 1997). These data suggest that the antinociceptive effect of systemically administered buprenorphine is mediated by the activation of -opioid receptors and that the analgesic effect of systemically administered buprenorphine is suppressed by concomitant activation of ORL1 receptors. On the other hand, spinal ORL1 receptor activation has been reported to produce an analgesic effect (Yamamoto et al., 1997(Yamamoto et al., , 1999).-Opioid receptors and ORL1 receptors are widely located in the nervous system, and there are not enough data to determine which -opioid receptor plays an important role in producing an analgesic effect of buprenorphine and which ORL1 receptor plays an important role in suppressing an analgesic effect of buprenorphine when buprenorphine is administered systemically. Moreover, it is possible that the analgesic effect of systemically administered buprenorphine can be attributed to the activation of spinal ORL1 receptors. In the present study, we investigated the analgesic effect of intrathecal (i.t.), intracerebroventricular (i.c.v.), or i.p. ad-

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BackgroundOlanzapine (OLZ) has become well-known for its antiemetic effects on chemotherapy-induced nausea and vomiting. However, it remains unclear whether OLZ also has efficacy for treating cancer-related anorexia. This study, therefore, retrospectively examined whether or not OLZ administration affects the food intake in anorexic cancer patients who exhibit neither nausea nor vomiting.MethodsEighty patients prescribed OLZ were extracted from 951 inpatients who consulted with our palliative care team at Chiba University Hospital from April 2008 to March 2016. Their food intake described on a nursing record was compared before and after OLZ administration. The observation period was 3 days before and after the start of OLZ treatment, because most inpatients whose food intake increased were discharged in 3 days.ResultsIn those 80 patients, the average dose of OLZ for 3 days was 2.28±0.87 (mean±SD) mg/day. First, the food intake in 80 patients was significantly higher after than before starting OLZ, and the relative change in food intake was 149% on average (P<0.0001, Student’s paired t-test). Second, OLZ increased the food intake even in 40 out of 80 patients without nausea or vomiting, and the relative change in food intake was 143% on average (P<0.001, Student’s paired t-test). Third, the average food intake increased in 13 out of 40 patients who were prescribed 1.5 mg/day of OLZ, and the relative change in food intake was 124% on average (P<0.01, Student’s paired t-test). There was no significant difference in food intake between a dose of 1.5 mg/day and a dose of >1.5 mg/day of OLZ (P=0.18, Welch’s unpaired t-test).ConclusionWe have herein reported OLZ’s ameliorating efficacy in cancer-related anorexia at the low dose of 1.5 mg/day. Although our study has many limitations, low-dose OLZ can be a promising treatment for cancer-related anorexia.