Usefulness of olanzapine as an adjunct to opioid treatment and for the treatment of neuropathic pain

Kazuhiro Torigoe, Kae Nakahara, Mahardian Rahmadi, Kazumi Yoshizawa, Hiroshi Horiuchi, Shigeto Hirayama, Satoshi Imai, Naoko Kuzumaki, Toshimasa Itoh, Akira Yamashita, Kiyoshi Shakunaga, Mitsuaki Yamasaki, Hiroshi Nagase, Motohiro Matoba, Tsutomu Suzuki, Minoru Narita

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

BACKGROUND:: The use of opioids for pain management is often associated with nausea and vomiting. Although conventional antipsychotics are often used to counter emesis, they can be associated with extrapyramidal symptoms. However, chronic pain can induce sleep disturbance. The authors investigated the effects of the atypical antipsychotic olanzapine on morphine-induced emesis and the sleep dysregulation associated with chronic pain. METHODS:: A receptor binding assay was performed using mouse whole brain tissue. The emetic response in ferrets was evaluated by counting retching and vomiting behaviors. Catalepsy in mice was evaluated by placing both of their forepaws over a horizontal bar. Released dopamine was measured by an in vivo microdialysis study. Sleep disturbance in mice in a neuropathic pain-like state was assayed by electroencephalogram and electromyogram recordings. RESULTS:: Olanzapine showed high affinity for muscarinic M1 receptor in brain tissue. Olanzapine decreased morphine-induced nausea and vomiting in a dose-dependent manner. However, olanzapine at a dose that had an antiemetic effect (0.03 mg/kg) did not induce catalepsy or hyperglycemia. In addition, olanzapine at this dose had no effect on the morphine-induced release of dopamine or inhibition of gastrointestinal transit. Finally, olanzapine inhibited thermal hyperalgesia and completely alleviated the sleep disturbance induced by sciatic nerve ligation. CONCLUSION:: These findings suggest that olanzapine may be useful for the treatment of morphine-induced emesis and as an adjunct for the treatment of neuropathic pain associated with sleep disturbance.

Original languageEnglish
Pages (from-to)159-169
Number of pages11
JournalAnesthesiology
Volume116
Issue number1
DOIs
Publication statusPublished - Jan 2012
Externally publishedYes

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