bisabolol and Nociceptive-Pain

The purposes of this study were to evaluate the anti-nociceptive effect of oral and topical administration of (-)-α-bisabolol (BISA) in rodent models of formalin- or cinnamaldehyde-induced orofacial pain and to explore the inhibitory mechanisms involved. Orofacial pain was induced by injecting 1.5% formalin into the upper lip of mice (20 μL) or into the temporomandibular joint (TMJ) of rats (50 μL). In another experiment, orofacial pain was induced with cinnamaldehyde (13.2 μg/lip). Nociceptive behavior was proxied by time (s) spent rubbing the injected area and by the incidence of head flinching. BISA (100, 200, or 400 mg/kg p.o. or 50, 100, or 200 mg/mL topical) or vehicle was administered 60 min before pain induction. The two formulations (lotion and syrup) were compared with regard to efficacy. The effect of BISA remained after incorporation into the formulations, and nociceptive behavior decreased significantly in all tests. The high binding affinity observed for BISA and TRPA1 in the molecular docking study was supported by in vivo experiments in which HC-030031 (a TRPA1 receptor antagonist) attenuated pain in a manner qualitatively and quantitatively similar to that of BISA. Blockers of opioid receptors, NO synthesis, and K

Topics: Acrolein; Administration, Oral; Administration, Topical; Analgesics; Animals; Behavior, Animal; Binding Sites; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Compounding; Facial Pain; Formaldehyde; Male; Mice; Molecular Docking Simulation; Monocyclic Sesquiterpenes; Nociception; Nociceptive Pain; Protein Binding; Protein Conformation; Rats, Wistar; Sesquiterpenes; Temporomandibular Joint; Transient Receptor Potential Channels; TRPA1 Cation Channel; TRPC Cation Channels

(-)-α-Bisabolol (BISA) is a sesquiterpene alcohol widely used as scent in cosmetic preparations, perfumes, shampoos, toilet soaps and other toiletries with potential for use in the pharmaceutical area.. To evaluate the corneal antinociceptive efficacy of BISA and to analyze the best solubilizing agent.. Acute corneal nociception was induced by the local application of hypertonic saline (5 M NaCl; 20 μL) to the corneal surface of Swiss mice (n = 8/group) 60 min after topical treatment with solutions or ointment containing BISA (50-200 mg/mL). The number of eye wipes performed with the ipsilateral forepaw was counted for a period of 30 s. Control groups (vehicles) were included.. BISA (50, 100 or 200 mg/mL) solubilized with Tween 80 did not reduce the number of eye wipes. Animals treated with the ointment (BISA 50, 100 or 200 mg/mL; p < 0.001), as well the solution containing propylene glycol (BISA 100 mg/mL; p < 0.05), showed significant reduction in the number of nociceptive behaviours. Solutions containing propylene glycol and isopropyl myristate had no effects.. BISA possess corneal antinociceptive activity. Although the ointment presented antinociceptive effect, it is concluded that BISA when associated with propylene glycol has better potential for corneal nociceptive pain since it is more comfortable to use, leading to greater acceptance by patients.

Topics: Administration, Ophthalmic; Analgesics; Animals; Behavior, Animal; Cornea; Disease Models, Animal; Drug Compounding; Excipients; Eye Pain; Mice; Monocyclic Sesquiterpenes; Nociceptive Pain; Ointments; Pain Measurement; Propylene Glycol; Saline Solution, Hypertonic; Sesquiterpenes; Solubility

Stachys lavandulifolia Vahl (Lamiaceae) is a medicinal plant widely used in Turkey and Iranian folk medicine due to its analgesic and anti-inflammatory properties, but little is known about its essential oil.. We studied the antinociceptive and anti-inflammatory effects of S. lavandulifolia essential oil (EOSl) and (-)-α-bisabolol (BIS), its main compound, in algogen-induced orofacial nociceptive behavior in mice, and assessed the possible involvement of pro-inflammatory cytokines in these profiles.. The GC-FID and GC-MS analysis of EOSl demonstrated the presence of (-)-α-bisabolol (56.4%), bicyclogermacrene (5.3%), δ-cadinene (4.2%) and spathulenol (2.9%) as the main compounds. Male Swiss mice were pretreated with EOSl (25 or 50mg/kg, p.o.), BIS (25 or 50mg/kg, p.o.), morphine (3mg/kg, i.p.) or vehicle (saline 0.9% with two drops of tween 80, 0.2%), before formalin- (20μl, 2%), capsaicin- (20μl, 2.5µg) or glutamate- (20μl, 25Mm) injection into the right upper lip (perinasal area) in mice. The anti-inflammatory profile of EOSl or BIS (50mg/kg) was assessed by the inflammatory response induced by carrageenan (2% in 0.2mL) in mice (pleurisy model).. Our results showed that p.o. treatment with EOSl and BIS displayed significant inhibitory (p<0.05 or p<0.01 or p<0.001) effects in different orofacial pain tests on mice, but BIS proved to be more effective, significantly reducing nociceptive behavior in all tests including both phases of the formalin test. The analgesic effect is not related to any abnormality since EOSl- or BIS-treated mice exhibited no performance alteration in grip strength. Moreover, EOS1 and BIS exhibited a significant anti-inflammatory effect (p<0.001) in the pleurisy model of inflammation, which seems to be related to a significant reduction (p<0.05) of the pro-inflammatory cytokine TNF-α in BIS treatment, and of the pro-inflammatory cytokine IL-1β (p<0.01) in EOS1 treatment.. Our results corroborate the use of S. lavandulifolia in traditional medicine as an analgesic and anti-inflammatory, which seems to be related to (-)-α-Bisabolol, the main compound of EOSl.

Topics: Analgesics; Animals; Anti-Infective Agents; Capsaicin; Carrageenan; Disease Models, Animal; Dose-Response Relationship, Drug; Facial Pain; Flame Ionization; Formaldehyde; Gas Chromatography-Mass Spectrometry; Glutamic Acid; Interleukin-1beta; Male; Mice; Monocyclic Sesquiterpenes; Nociception; Nociceptive Pain; Oils, Volatile; Phytotherapy; Plant Extracts; Plant Oils; Plants, Medicinal; Pleurisy; Sesquiterpenes; Stachys; Time Factors; Tumor Necrosis Factor-alpha