Management of opioid-induced pruritus: a role for 5-HT3 antagonists?

Kyriakides, K; Hussain, Sarfaraj; Hobbs, Gregory J.

doi:10.1093/bja/82.3.439

Cited by 70 publications

(25 citation statements)

References 8 publications

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“…Moreover, as the activation of 5-HT3R is relevant for pain perception, the expression of 5-HT3R in the dorsal horn of the spinal cord has also been well investigated616263646566676869707172. Our data showing strong expression of 5-HT3R in the superficial layers of the dorsal horn of the spinal cord are consistent with data from previous studies13262831486073.…”

Section: Discussionsupporting

confidence: 91%

Building a 5-HT3A Receptor Expression Map in the Mouse Brain

Koyama

Kondo

Shimada

2017

Sci Rep

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Of the many serotonin receptors, the type 3 receptors (5-HT3R) are the only ionotropic ones, playing a key role in fast synaptic transmission and cognitive and emotional brain function through controlled neuronal excitation. To better understand the various functions of 5-HT3Rs, it is very important to know their expression pattern in the central nervous system (CNS). To date, many distributional studies have shown localized 5-HT3R expression in the brain and spinal cord. However, an accurate pattern of 5-HT3R expression in the CNS remains to be elucidated. To investigate the distribution of 5-HT3R in the mouse brain in detail, we performed immunofluorescent staining using 5-HT3AR-GFP transgenic mice. We found strong 5-HT3AR expression in the olfactory bulb, cerebral cortex, hippocampus, and amygdala; and partial expression in the pons, medulla, and spinal cord. Meanwhile, the thalamus, hypothalamus, and midbrain exhibited a few 5-HT3AR-expressing cells, and no expression was detected in the cerebellum. Further, double-immunostaining using neural markers confirmed that 5-HT3AR is expressed in GABAergic interneurons containing somatostatin or calretinin. In the present study, we built a 5-HT3AR expression map in the mouse brain. Our findings make significant contributions in elucidating the novel functions of 5-HT3R in the CNS.

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Section: Discussionsupporting

confidence: 91%

Building a 5-HT3A Receptor Expression Map in the Mouse Brain

Koyama

Kondo

Shimada

2017

Sci Rep

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“…significantly reduced the incidence of scratching (42.5 vs. 70% in the placebo group, P = 0.013). The incidence of itching in the ondansetron group was less than that in the placebo group but the difference was not statistically significant (30 vs. 42.5%, respectively, P = 0.245) (36).…”

Section: Pruritusmentioning

confidence: 73%

“…For example, ondansetron was effective as an antidiarrheal agent in carcinoid syndrome (70). Opiate-induced postoperative pruritus has also been successfully treated with ondansetron (10,36). Recently, 5-HT 3 antagonism was found to be effective in controlling postoperative shivering in normothermic patients (9).…”

Section: New Indicationsmentioning

confidence: 99%

Ondansetron: A Selective 5‐HT₃ Receptor Antagonist and Its Applications in CNS‐Related Disorders

2001

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Ondansetron is a selective 5-hydroxytryptamine 3 (5-HT 3 ) receptor antagonist that has been introduced to clinical practice as an antiemetic for cancer treatment-induced and anesthesia-related nausea and vomiting. Its use under these circumstances is both prophylactic and therapeutic. It has a superior efficacy, safety and pharmacoeconomic profile compared with other groups of antiemetics, namely antidopaminergics, antihistamines and anticholinergics. However, its place in the management of anticipatory and delayed vomiting in cancer treatment and as a rescue antiemetic in surgical patients needs to be further explored. Furthermore, recent animal and human research also reflects its possible novel application in the treatment of other disease states, such as alcoholism, cocaine addiction, opioid withdrawal syndrome, anxiety disorders, gastrointestinal motility disorders, Tourette's syndrome and pruritus. This review revisits the widespread physiological and pathological effects of 5-HT and discusses both the basic science literature and the clinical developments responsible for the conventional and novel uses of ondansetron. In addition, new discoveries relating to the effects of ondansetron on other receptors/channels and their possible therapeutic applications are presented.

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“…Pharmacological and genetic ablation studies have shown that HTR1a, HTR1b, HTR2a, HTR2b and HTR3a mediate some forms of acute and inflammatory pain transmission (Abbott et al, 1996; Kayser et al, 2007; Lin et al, 2011; Nojima and Carstens, 2003; Van Steenwinckel et al, 2008; Zeitz et al, 2002). Pharmacological studies have also implicated peripheral HTR2a, HTR2b and HTR3 receptors, and central HTR1a receptors in itch (Bonnet et al, 2008; Imamachi et al, 2009; Kyriakides et al, 1999; Liu et al, 2013; Zhao et al, 2014), but to date there has been no genetic evidence for any 5-HT receptor in transducing serotonergic itch signals in primary afferent neurons. We have used genetic and pharmacological tools to show that HTR7 plays a selective role in acute serotonergic and atopic dermatitis itch, but not pain.…”

Section: Discussionmentioning

confidence: 99%

HTR7 Mediates Serotonergic Acute and Chronic Itch

Morita

McClain

Batia

et al. 2015

Neuron

168

172

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SUMMARY Chronic itch is a prevalent and debilitating condition for which few effective therapies are available. We harnessed the natural variation across genetically distinct mouse strains to identify transcripts co-regulated with itch behavior. This survey led to the discovery of the serotonin receptor, HTR7, as a key mediator of serotonergic itch. Activation of HTR7 promoted opening of the ion channel TRPA1, which in turn triggered itch behaviors. In addition, acute itch triggered by serotonin or a selective serotonin reuptake inhibitor required both HTR7 and TRPA1. Aberrant serotonin signaling has long been linked to a variety of human chronic itch conditions, including atopic dermatitis. In a mouse model of atopic dermatitis, mice lacking HTR7 or TRPA1 displayed reduced scratching and skin lesion severity. These data highlight a role for HTR7 in acute and chronic itch, and suggest that HTR7 antagonists may be useful for treating a variety of pathological itch conditions.

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Management of opioid-induced pruritus: a role for 5-HT3 antagonists?

Cited by 70 publications

References 8 publications

Building a 5-HT3A Receptor Expression Map in the Mouse Brain

Building a 5-HT3A Receptor Expression Map in the Mouse Brain

Ondansetron: A Selective 5‐HT₃ Receptor Antagonist and Its Applications in CNS‐Related Disorders

HTR7 Mediates Serotonergic Acute and Chronic Itch

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Management of opioid-induced pruritus: a role for 5-HT3 antagonists?

Cited by 70 publications

References 8 publications

Building a 5-HT3A Receptor Expression Map in the Mouse Brain

Building a 5-HT3A Receptor Expression Map in the Mouse Brain

Ondansetron: A Selective 5‐HT3 Receptor Antagonist and Its Applications in CNS‐Related Disorders

HTR7 Mediates Serotonergic Acute and Chronic Itch

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Product

Resources

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Ondansetron: A Selective 5‐HT₃ Receptor Antagonist and Its Applications in CNS‐Related Disorders