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Background: Nociceptive and inflammatory orofacial pain is highly prevalent in the population, which justifies the search for safer analgesics. There is increasing evidence of the analgesic and anxiolytic potential of Lavandula angustifolia essential oil (LAV EO), which may represent, when administered through inhalation, may represent a safer alternative for pain treatment., Objective: to evaluate whether LAV EO has antinociceptive effect in the formalin test, and anti-hyperalgesic and anxiolytic-like effects in rats subjected to a model of orofacial postoperative pain., Methodology: Female Wistar rats were exposed to LAV EO (5%) by inhalation for 30 minutes. After exposure, animals were injected with formalin (2.5%, 50 μL) or saline into the hind paw or upper lip and the number of flinches or facial grooming time, respectively, were evaluated. Likewise, on day 3 after intraoral mucosa incision, the animals were exposed to LAV EO and facial mechanical, and heat hyperalgesia were assessed. The influence of LAV EO inhalation on anxiety-like behavior was assessed in operated rats by testing them on the open field (OF) and elevated plus maze (EPM)., Results: LAV EO reduced the phase II of the paw formalin test and both phases of the orofacial formalin test. On day three post-incision, LAV EO reduced heat and mechanical hyperalgesia, from 30 minutes up to three hours, and reduced the anxiety-like behavior in operated rats without causing locomotor deficit., Conclusion: LAV EO inhalation results in antinociceptive and anxiolytic-like effects in orofacial pain models, which encourages further studies on LAV EO indications and effectiveness on orofacial pain conditions.

Trigeminal neuralgia (TN) is a severe form of neuropathic pain frequently associated with anxiety. The chronic constriction injury of the infraorbital nerve (CCI-ION) of rodents is a well-established model to study sensory alterations related to TN. However, few studies have addressed the emotional component of pain, which is fundamental to increase its translational capability. Emission of ultrasonic vocalization (USV) is considered a reliable measure of the emotional state of rats. Rats emit 50-kHz USVs in social and appetitive situations, whereas 22-kHz USVs may index a negative state. Studies suggest that persistent pain causes reduction in 50-kHz calls, but this may also indicate anxiety-like behavior. Thus, we hypothesize that CCI-ION would decrease 50-kHz calls and that pharmacological pain relief would restore USVs, without interfering with anxiety-like behavior. On day 15 after surgery, male rats were treated with local lidocaine, midazolam or carbamazepine to determine their effect on facial mechanical hyperalgesia, USV and anxiety-like behavior. The results showed that CCI-ION induced hyperalgesia, which was attenuated by lidocaine or carbamazepine, developed anxiety-like behavior, which was reduced only by midazolam, and displayed a reduced number of 50-kHz calls, compared to sham. Lidocaine and carbamazepine increased 50-kHz calls emitted by CCI-ION rats, but midazolam failed to change them. These data add information on the translational aspects of CCI-ION model and carbamazepine treatment for trigeminal neuropathic pain. Furthermore, they suggest that the reduction of USV in persistent pain conditions is related to spontaneous pain and reinforce the idea that it reflects the emotional component of pain., (Copyright © 2022 Elsevier B.V. All rights reserved.)

It has been shown that kappa opioid receptor (KOR) antagonists, such as nor-binaltorphimine (nor-BNI), have antinociceptive effects in some pain models that affect the trigeminal system. Also, its anxiolytic-like effect has been extensively demonstrated in the literature. The present study aimed to investigate the systemic, local, and central effect of nor-BNI on trigeminal neuropathic pain using the infraorbital nerve constriction model (CCI-ION), as well as to evaluate its effect on anxiety-like behavior associated with this model. Animals received nor-BNI systemically; in the trigeminal ganglion (TG); in the subarachnoid space to target the spinal trigeminal nucleus caudalis (Sp5C) or in the central amygdala (CeA) 14 days after CCI-ION surgery. Systemic administration of nor-BNI caused a significant reduction of facial mechanical hyperalgesia and promoted an anxiolytic-like effect, which was detected in the elevated plus-maze and the light-dark transition tests. When administered in the TG or CeA, the KOR antagonist was able to reduce facial mechanical hyperalgesia induced by CCI-ION, but without changing the anxiety-like behavior. Moreover, no change was observed on nociception and anxiety-like behavior after nor-BNI injection into the Sp5C. The present study demonstrated antinociceptive and anxiolytic-like effects of nor-BNI in a model of trigeminal neuropathic pain. The antinociceptive effect seems to be dissociated from the anxiolytic-like effect, at both the sites involved and at the dose need to achieve the effect. In conclusion, the kappa opioid system may represent a promising target to be explored for the control of trigeminal pain and associated anxiety. However, further studies are necessary to better elucidate its functioning and modulatory role in chronic trigeminal pain states., (Copyright © 2021. Published by Elsevier B.V.)

Acute pain that persists for a few days is associated with a reduction in patients' quality of life. Orofacial persistent pain promotes psychological disorders such as anxiety, impairs daily essential activities such as eating, and results in decreased social interaction. Here, we investigated whether rats subjected to orofacial formalin injection or intraoral incision surgery display persistent facial heat hyperalgesia, ongoing pain, anxiety-like behavior, and changes in ultrasonic vocalization. Orofacial formalin injection or intraoral incision caused facial heat hyperalgesia for 3 days compared with saline-injected and sham animals. In addition, both experimental groups showed a reduction in the number of entries and in the time spent in the open arms in the elevated plus maze test on day 3, suggesting that anxiety-like behavior developed as a consequence of persistent pain. At this time point, both groups also displayed a reduction in the number of 50-kHz calls, specifically in the flat subtype, which suggests a decrease in social communication. Moreover, on day 3 after surgery, systemic morphine produced robust conditioned place preference in rats subjected to intraoral incision compared with sham, and the former group also presented increased spontaneous facial grooming, revealing the presence of ongoing pain. Finally, Western blot and immunohistochemistry analysis showed a reduction in tyrosine hydroxylase expression in the nucleus accumbens, which may reflect a decrease in mesolimbic dopaminergic activity. Altogether, the results demonstrate that acute orofacial pain causes prolonged changes in behavioral and affective pain components, which may be related to dopaminergic changes in the nucleus accumbens.