Intraplantar injection of linalool reduces paclitaxel-induced acute pain in mice

Linalool is the principal component of many essential oils known to possess biological activities. We previously reported that intraplantar injection of linalool reduces the nociceptive response as assayed by the capsaicin test. In this study, we sought to determine whether intraplantar injection of linalool could influence the induction of acute pain (allodynia and hyperalgesia) by paclitaxel in mice. Paclitaxel is widely used in cancer chemotherapy for the treatment of solid tumors, but it sometimes induces moderate to severe acute pain. Paclitaxel administered intraperitoneally as a single dose of 5, 10 or 20 mg/kg produced mechanical allodynia and hyperalgesia in mice. Paclitaxel-induced mechanical allodynia and hyperalgesia began 1 day after administration of paclitaxel and resolved within 7 days. Linalool injected into the hindpaw caused a significant reduction in paclitaxel-induced mechanical allodynia and hyperalgesia. Pretreatment with naloxone hydrochloride, an opioid receptor antagonist, or naloxone methiodide, a peripherally acting μ-opioid receptor-preferring antagonist, significantly reversed linalool-induced antiallodynia and antihyperalgesia. Our results provide evidence for the involvement of peripheral opioids in antiallodynia and antihyperalgesia induced by linalool. These results suggest that activation of peripheral opioid receptors may play an important role in reducing paclitaxel-induced mechanical allodynia and hyperalgesia.