The Antinociceptive Effect of (-)-Linalool in Models of Chronic Inflammatory and Neuropathic Hypersensitivity in Mice

Batista, P.; Werner, Maria Fernanda de Paula; Oliveira, Erica Carvalho; Burgos, Leonel; Pereira, Patrı́cia; Brum, Lucimar Filot da Silva; Story, Gina M.; Santos, Adair R.S.

doi:10.1016/j.jpain.2010.02.022

Cited by 117 publications

(73 citation statements)

References 48 publications

(45 reference statements)

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“…Linalool is the naturally occurring enantiomer of the monoterpene compound found in a volatile component of the essential oil extracted from aromatic plants, sage, lavender, rosewood, thyme and bergamot. As previously reported (2,3,(22)(23)(24), (−) linalool administration produces antiinflammatory and antinociceptive activities in several behavioral assays. We recently reported that subcutaneous (s.c.) injection of capsaicin into the hindpaw produced a short-lasting paw-licking/biting response, which was dose-dependently inhibited by intraplantarly administered linalool (28).…”

supporting

confidence: 76%

“…Nonsteroidal antiinflammatory drugs, acetaminophen (15), Shakuyaku-Kanzo-To (a Japanese herb) (11), corticosteroids (17), antihistamines (18), opioids (29) and amifostine (10) have all been tested in the treatment of paclitaxel-induced acute pain but the findings of these studies have not been definitive. Linalool has been shown to be effective as an antinociceptive compound in several nociceptive assays (2,3,(22)(23)(24). Linalool inhibited the biting response induced by intrathecal injection of IL-1β or TNF-α (2).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2012

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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

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confidence: 76%

Section: Discussionmentioning

confidence: 99%

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

et al. 2012

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“…Linalool is a monoterpene compound and is the main volatile component of the essential oils of various plants, including BEO. It has previously been reported that linalool administration produced antibacterial, anticonvulsant, and anti-inflammatory effects, as well as showing antinociceptive activity in several behavioral assays (2)(3)(4)(16)(17)(18)(19)(20). Furthermore, linalool can significantly reduce both mor-Italy).…”

mentioning

confidence: 98%

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

et al. 2015

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This study investigated the effect of bergamot essential oil (BEO) or linalool, a major volatile component of BEO, on the nociceptive response to formalin. Plantar subcutaneous injection of BEO or linalool into the ipsilateral hindpaw reduced both the first and late phases of the formalininduced licking and biting responses in mice. Plantar subcutaneous injection of BEO or linalool into the contralateral hindpaw did not yield an antinociceptive effect, suggesting that the antinociceptive effect of BEO or linalool in the formalin test occurred peripherally. Intraperitoneal and plantar subcutaneous injection pretreatment with naloxone hydrochloride, an opioid receptor antagonist, significantly attenuated both BEO-and linalool-induced antinociception. Pretreatment with naloxone methiodide, a peripherally acting opioid receptor antagonists, also significantly antagonized the antinociceptive effects of BEO and linalool. Our results provide evidence for the involvement of peripheral opioids in antinociception induced by BEO and linalool. These results suggest that activation of peripheral opioid receptors may play an important role in reducing formalin-induced nociception.The essential oil of bergamot (BEO; Citrus bergamia Risso) is one of the most commonly used essential oils and is familiar to most of the general public. BEO is obtained by cold pressing of the epicarp and part of the mesocarp of the fresh bergamot fruit. BEO consists of a volatile (93-96%) and a nonvolatile fraction (4-7%); the former contains monoterpene and sesquiterpene hydrocarbons and oxygenated derivatives such as linalool and linalyl acetate, while the latter fraction contains waxes, polymethoxylated flavones, coumarins, and psoralens such as bergamottin and bergapten (6,14). BEO has been reported to minimize symptoms of stress-induced anxiety and mild mood disorders, as well as cancer pain, however the mechanistic basis for its use in such applications awaits discovery (1). A previous in vitro study showed that BEO reduced neuronal damage caused by excitotoxic stimuli (5), and significantly increased the extracellular levels of the inhibitory amino acid neurotransmitter gamma-aminobutyric acid (GABA) in rat hippocampus (15). Linalool is a monoterpene compound and is the main volatile component of the essential oils of various plants, including BEO. It has previously been reported that linalool administration produced antibacterial, anticonvulsant, and anti-inflammatory effects, as well as showing antinociceptive activity in several behavioral assays (2)(3)(4)(16)(17)(18)(19)(20). Furthermore, linalool can significantly reduce both mor-

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“…Treatments of some painful conditions, such as inflammatory and neurogenic pain, are often unsatisfactory because its etiology is heterogeneous and the underlying pathophysiology mechanisms are complex (Batista et al, 2010). Moreover, currently available drugs that provide relief from these painful conditions are effective only in a fraction of patients.…”

Section: Introductionmentioning

confidence: 99%

“…In general, these drugs present low efficacy and numerous side effects (Basbaum, 1999;Mendell & Sahenk, 2003). In this context, natural products that present fewer side effects emerge as interesting therapeutic resources for the development of new drugs for the management of certain painful states (McCurdy & Scully, 2005;Batista et al, 2010). …”

Section: Introductionmentioning

confidence: 99%

Citral reduces nociceptive and inflammatory response in rodents

Quintans‐Júnior¹,

Guimarães²,

Santana³

et al. 2011

Rev. bras. farmacogn.

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Citral (CIT), which contains the chiral enantiomers, neral (cis) and geranial (trans), is the majority monoterpene from Lippia alba and Cymbopogon citratus. The present study aimed to evaluate CIT for antinociceptive and antiinflammatory activities in rodents. Antinociceptive and anti-inflammatory effects were studied by measuring nociception through acetic acid and formalin tests, while inflammation was verified by inducing peritonitis and paw edema with carrageenan. All tested doses of CIT had significant protection (p<0.001) against acetic acid (0.8%) induced nociceptive behavior and the effects were also similar to morphine while formalin induced nociception was significantly protected (p<0.05) only at higher dose (200 mg/kg) of CIT in the first phase of the test. CIT significantly reduce (p<0.001) nociceptive behavior emanating from inflammation in second phase at all the doses.The pretreatment with CIT (100 and 200 mg/kg) significantly reduced the paw edema induced by carrageenan. Moreover, systemic treatment with CIT (100 and 200 mg/kg) significantly reduced (p<0.001) the leukocyte migration in the carrageenaninduced migration to the peritoneal cavity. Our investigation shows that CIT possess significant central and peripheral antinociceptive effects. It was also verified an anti-inflammatory activity. All together these results suggest that CIT might represent important tool for treatment of painful conditions.

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The Antinociceptive Effect of (-)-Linalool in Models of Chronic Inflammatory and Neuropathic Hypersensitivity in Mice

Cited by 117 publications

References 48 publications

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

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

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

Citral reduces nociceptive and inflammatory response in rodents

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