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

Abstract

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.The major classes of antineoplastic agents-the vinca alkaloids, taxanes, bortezomib and platinum-derived compounds-are associated with the development of dose-limiting neuropathic pain (12, 32). Paclitaxel is a taxane chemotherapeutic commonly used for the treatment of solid tumors and ovarian and breast cancers. Paclitaxel acts as an antimitotic by stabilizing microtubules against disassembly, thus inhibiting the cell cycle in late mitosis and ultimately inducing apoptosis (30). Peripheral neuropathy sometimes occurs as a side-effect of chemotherapeutic treatment with paclitaxel and often manifests as bilateral pain in the extremities in a stocking and glove-type distribution (5). This pain can greatly reduce patients' quality of life and affect activities of daily living. Furthermore, paclitaxel therapy often results in acute pain (16,21). Acute pain begins 1-3 days after the commencement of treatment with paclitaxel, resolves within 7 days and affects mostly the large axial muscular and joint regions (15). Paclitaxel-induced acute pain following paclitaxel infusion has commonly been treated with nonsteroidal antiinflammatory drugs, acetaminophen and opioid pain medications (15). In addition, ShakuyakuKanzo-To (a Japanese herb) (11), corticosteroids (17), antihistamines (18), opioids (29) and amifostine (10) have been investigated for the prevention

Paclitaxel-induced hyposensitivity to nociceptive chemical stimulation in mice can be prevented by treatment with minocycline

“…), in a volume of 10 μl/g body mass, once per day for 5 consecutive days. Other groups and ours have observed that this treatment regimen produce thermal hyperalgesia in mice 20 21 22 23 24 .…”

“…The paclitaxel treatment regimen and dose used in this study has been reported to produce painful neuropathy in mice, which manifested as thermal hyperalgesia, cold allodynia and mechanical allodynia 21 22 23 . Our group also previously observed thermal hyperalgesia using the same paclitaxel treatment regimen 20 24 .…”

<b>Effect of plantar subcutaneous administration of bergamot essential oil and linalool on formalin-induced nociceptive behavior in </b><b>mice </b>

“…the acute pain models (11,23), suggesting that BEO and linalool may be effective in reducing nociception linked to a range of paradigms. The present data suggest that plantar subcutaneous injection of BEO or linalool significantly reduces formalin-induced nociception.…”

“…BEO and linalool were diluted in jojoba wax (Simmondsia chinensis) (K.S.A. International Co. Ltd., Kanagawa, Japan) to reach total amounts of 1.25-10 μg (11,23). Jojoba wax alone had no effect on formalin-induced nociception.…”

Terpenoids, Cannabimimetic Ligands, beyond the Cannabis Plant

“…Linalool has also reported to be protective against ultraviolet B (UVB)-induced tumor through inhibition of inflammation and angiogenesis signaling, as well as induction of apoptosis in the mouse skin [118]. Finally, a study showed that linalool reduced paclitaxel-induced acute pain in mice, which was antagonized by the direct injection of naloxone hydrochloride, suggesting opioid signaling modulation [119]. What can be appreciated so far, and will continue to be addressed, is the general ability of different terpenes to modulate inflammation and oxidative stress through different pathways, which in turn could be very useful to shed light to novel treatments for pain, cancer, autoimmune diseases, and CNS diseases that rely greatly on the impact of these processes.…”