Itching after intrathecal morphine. Incidence and treatment

Slappendel, R.; Weber, E. W. G.; Benraad, B.; Limbeek, Jacques van; Dirksen, R.

doi:10.1097/00003643-200010000-00004

Cited by 30 publications

(23 citation statements)

References 16 publications

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“…Similar to the results obtained in previous studies, the topical application of 5-HT evoked scratch behavior, which was reduced by prior application of naloxone, known to enhance the sensation of pain. In agreement with this finding, it is well known that intrathecal injection of an opioid initiates an itch sensation that can be blocked by naloxone (Hales 1980;Jeon et al 2005;Maxwell et al 2005;Slappendel et al 2000). When 5-HT was injected into the hindpaw, rats bit the injected region instead of scratching, since it is difficult for them to scratch their hindpaw (Kuraishi et al 2008).…”

Section: Discussionmentioning

confidence: 57%

“…Itch stimuli evoke scratching or biting, whereas noxious stimuli evoke a withdrawal reflex, flinching, or licking (Kuraishi et al 1995(Kuraishi et al , 2008Nojima et al 2004). Opioids, which are commonly used for alleviation of pain, elicit itching (Hales 1980;Jeon et al 2005;Maxwell et al 2005;Slappendel et al 2000); conversely, the opioid receptor antagonist naloxone enhances pain but inhibits the itch sensation (Metze et al 1999;Robertson et al 2008). …”

Section: Introductionmentioning

confidence: 99%

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Responsiveness of C Neurons in Rat Dorsal Root Ganglion to 5-Hydroxytryptamine-Induced Pruritic Stimuli In Vivo

Hachisuka

Furue²,

Furue

et al. 2010

Journal of Neurophysiology

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Hachisuka J, Furue H, Furue M, Yoshimura M. Responsiveness of C neurons in rat dorsal root ganglion to 5-hydroxytryptamine-induced pruritic stimuli in vivo. J Neurophysiol 104: 271-279, 2010. First published May 19, 2010 doi:10.1152/jn.00938.2009. Itching is a common symptom in dermatologic diseases and causes restless scratching of the skin, which aggravates the condition. The mechanism of the itch sensation, however, is enigmatic. The present study included behavioral tests and electrophysiological recordings from rat dorsal root ganglion (DRG) neurons in vivo to analyze the response to pruritic stimuli induced by topical application of 5-hydroxytryptamine (5-HT) to the skin. Topically applied 5-HT to the rostral back evoked scratching, whereas application of the vehicle did not. Following subcutaneous injection of the opioid receptor antagonist naloxone, the number of scratches decreased, suggesting that the scratching was preferentially mediated by itch but not pain sensation. To elucidate the firing properties of DRG neurons in response to topically applied 5-HT, intracellular recordings were made from DRG neurons in vivo. None of the A␤ and A␦ neurons responded to 5-HT; in contrast, 25 of 91 C neurons (27%) exhibited repetitive firing in response to 5-HT, which could be classified into two firing patterns: one was a transient type, characterized by low firing frequency that decreased within 5 min; the other was a long-lasting type, having high firing frequency that continued increasing after 5 min. The time course of the firing pattern of long-lasting C neurons was comparable to the scratching behavior. Intriguingly, the long-lasting-type neurons had a significantly smaller fast afterhyperpolarization than that of the 5-HTinsensitive neurons. These observations suggest that the long-lastingfiring C neurons in rat DRG sensitive to 5-HT are responsible for conveying pruritic information to the spinal cord.

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Section: Discussionmentioning

confidence: 57%

Section: Introductionmentioning

confidence: 99%

Responsiveness of C Neurons in Rat Dorsal Root Ganglion to 5-Hydroxytryptamine-Induced Pruritic Stimuli In Vivo

Hachisuka

Furue²,

Furue

et al. 2010

Journal of Neurophysiology

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“…Opioids are pruritogens, and itch is a limiting side effect of intrathecal opiate analgesics (8). Naloxone inhibited DCA-induced scratching, implicating MOR in the central transmission of BAinduced itch ( Figure 10A).…”

Section: Discussionmentioning

confidence: 99%

“…Itch and pain are antagonistic: painful stimuli (scratching) relieve itch (7), and analgesics (intrathecal morphine) can cause itch (8). However, itch and pain are related because they both protect against irritating and damaging stimuli, and they share a similar mechanism of transmission: pruritogens and algesic substances are sensed in the skin by primary spinal afferent neurons of the dorsal root ganglia (DRG), which transmit information to the brain via second-order neurons in the dorsal horn of the spinal cord (6).…”

Section: Introductionmentioning

confidence: 99%

The TGR5 receptor mediates bile acid–induced itch and analgesia

et al. 2013

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Patients with cholestatic disease exhibit pruritus and analgesia, but the mechanisms underlying these symptoms are unknown. We report that bile acids, which are elevated in the circulation and tissues during cholestasis, cause itch and analgesia by activating the GPCR TGR5. TGR5 was detected in peptidergic neurons of mouse dorsal root ganglia and spinal cord that transmit itch and pain, and in dermal macrophages that contain opioids. Bile acids and a TGR5-selective agonist induced hyperexcitability of dorsal root ganglia neurons and stimulated the release of the itch and analgesia transmitters gastrin-releasing peptide and leucineenkephalin. Intradermal injection of bile acids and a TGR5-selective agonist stimulated scratching behavior by gastrin-releasing peptide-and opioid-dependent mechanisms in mice. Scratching was attenuated in Tgr5-KO mice but exacerbated in Tgr5-Tg mice (overexpressing mouse TGR5), which exhibited spontaneous pruritus. Intraplantar and intrathecal injection of bile acids caused analgesia to mechanical stimulation of the paw by an opioid-dependent mechanism. Both peripheral and central mechanisms of analgesia were absent from Tgr5-KO mice. Thus, bile acids activate TGR5 on sensory nerves, stimulating the release of neuropeptides in the spinal cord that transmit itch and analgesia. These mechanisms could contribute to pruritus and painless jaundice that occur during cholestatic liver diseases.

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“…The incidence and severity of this pruritus has been shown to be a dose-related effect [4], and is generally accepted to occur most frequently in obstetric patients [2]. The prevalence of pruritus is also related to the time of intrathecal injection of morphine, the highest being found between 3 and 9 h following morphine administration [4][5][6][7][8].…”

mentioning

confidence: 99%

Subcutaneous naloxone for the prevention of intrathecal morphine induced pruritus in elective Caesarean delivery*

Lockington

Fa'aea

2007

Anaesthesia

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SummaryThe aim of this study was to assess the antipruritic efficacy of subcutaneous naloxone following intrathecal morphine administration. Fifty women undergoing elective Caesarean section using spinal anaesthesia were randomly allocated, in a double-blind study design, to receive either naloxone 400 lg or placebo as a subcutaneous injection at the end of surgery. Spinal anaesthesia was performed using 0.5% hyperbaric bupivacaine, 25 lg fentanyl and 150 lg of preservative-free morphine sulphate. The primary outcome measures were: incidence of pruritus, nausea and vomiting, and quality of analgesia. The incidence of pruritus and nausea and vomiting was not significantly different between the two groups. There was also no significant difference in postoperative analgesia between the two groups. We conclude that pruritus, following intrathecal fentanyl 25 lg and preservative-free morphine sulphate 150 lg, is not reduced by the addition of naloxone 400 lg administered subcutaneously on the completion of surgery.

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Itching after intrathecal morphine. Incidence and treatment

Cited by 30 publications

References 16 publications

Responsiveness of C Neurons in Rat Dorsal Root Ganglion to 5-Hydroxytryptamine-Induced Pruritic Stimuli In Vivo

Responsiveness of C Neurons in Rat Dorsal Root Ganglion to 5-Hydroxytryptamine-Induced Pruritic Stimuli In Vivo

The TGR5 receptor mediates bile acid–induced itch and analgesia

Subcutaneous naloxone for the prevention of intrathecal morphine induced pruritus in elective Caesarean delivery*

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