Essential oils for treating anxiety: a systematic review of randomized controlled trials and network meta-analysis.

Background and purpose: The findings of clinical studies exploring essential oils (EOs) for anxiety remain disputed, and no studies have yet clarified the differences in the efficacy of EOs. The purpose of the study was to directly or indirectly compare the efficacy of different types of EOs on anxiety by pooling the results of randomized controlled trials (RCTs). Methods: PubMed, Cochrane Library, Embase, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from inception to November 2022. Only full texts of RCTs that investigated the effects of EOs on anxiety were included. The trial data were extracted and the risk of bias was assessed by two reviewers independently. Pairwise meta-analysis and network meta-analysis were performed by Stata 15.1 or R 4.1.2 software. Results: Forty-four RCTs (fifty study arms) involving 10 kinds of EOs and 3419 anxiety patients (1815 patients in EOs group and 1604 patients in control group) were included. Pairwise meta-analyses showed that EOs were effective in reducing State Anxiety Inventory scores (SAIS) [WMD = -6.63, 95% CI-8.17, -5.08] and Trait Anxiety Inventory scores (TAIS) [WMD = -4.97, 95% CI-6.73, -3.20]. Additionally, EOs could decrease systolic blood pressure (SBP) [WMD = -6.83, (95% CI -10.53, -3.12), P < 0.001] and heart rate (HR) [WMD = -3.43, (95% CI -5.51, -1.36), P < 0.001]. Network meta-analyses demonstrated that regarding the outcome of SAIS, Jasminum sambac (L.)Ait. (jasmine) was the most effective with a weighted mean difference (WMD) of-13.61 (95% CrI-24.79, -2.48). Followed by Citrus (citrus aurantium L.), which had a WMD of-9.62 (95% CrI-13.32, -5.93). Moderate effect sizes were observed for Rosa rugosa Thunb. (damask rose) (WMD = -6.78, 95% CrI-10.14, -3.49) and Lavandula angustifolia Mill. (lavender) (WMD = -5.41, 95% CrI-7.86, -2.98). Regarding the results of TAIS, citrus aurantium L. was the best ranked intervention with a WMD of-9.62 (95% CrI-15.62, -3.7). Moderate-to-large effect sizes were observed for Citrus limon (L.) Burm. F. (lemon) (WMD:-8.48; 95% CrI-16.67, -0.33) and lavender (WMD:-5.5; 95% CrI-8.7, -2.46). Conclusion: According to the comprehensive analysis, EOs are effective in reducing both state anxiety and trait anxiety, and citrus aurantium L. essential oil seems to be the most recommended type of EO for treating anxiety because of its significant effects in reducing SAIS and TAIS. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022331319.

Reduced GABAergic transmission in the ventrobasal thalamus contributes to thermal hyperalgesia in chronic inflammatory pain.

The ventrobasal (VB) thalamus is innervated by GABAergic afferents from the thalamic reticular nucleus (TRN) and participates in nociception. But how the TRN-VB pathway regulates pain is not fully understood. In the present study, we reported decreased extracellular GABA levels in the VB of rats with CFA-induced chronic inflammatory pain, measured by microdialysis with HPLC analysis. In vitro whole-cell patch-clamp recording showed decreased amplitudes of tonic currents, increased frequencies of mIPSCs, and increased paired-pulse ratios in thalamic slices from chronic inflammatory rats (7 days). Microinjection of the GABAAR agonist muscimol and optogenetic activation of the TRN-VB pathway relieved thermal hyperalgesia in chronic inflammatory pain. By contrast, microinjecting the extrasynaptic GABAAR agonist THIP or selective knockout of synaptic GABAAR γ2 subunits aggravated thermal hyperalgesia in the chronic stage of inflammatory pain. Our findings indicate that reduced GABAergic transmission in the VB contributes to thermal hyperalgesia in chronic inflammatory pain, which could be a synaptic target for pharmacotherapy.

Shp-1 dephosphorylates TRPV1 in dorsal root ganglion neurons and alleviates CFA-induced inflammatory pain in rats.

Transient receptor potential vanilloid 1 (TRPV1) receptors are expressed in nociceptive neurons of rat dorsal root ganglions (DRGs) and mediate inflammatory pain. Nonspecific inhibition of protein-tyrosine phosphatases (PTPs) increases the tyrosine phosphorylation of TRPV1 and sensitizes TRPV1. However, less is known about tyrosine phosphorylation's implication in inflammatory pain, compared with that of serine/threonine phosphorylation. Src homology 2 domain-containing tyrosine phosphatase 1 (Shp-1) is a key phosphatase dephosphorylating TRPV1. In this study, we reported that Shp-1 colocalized with and bound to TRPV1 in nociceptive DRG neurons. Shp-1 inhibitors, including sodium stibogluconate and PTP inhibitor III, sensitized TRPV1 in cultured DRG neurons. In naive rats, intrathecal injection of Shp-1 inhibitors increased both TRPV1 and tyrosine-phosphorylated TRPV1 in DRGs and induced thermal hyperalgesia, which was abolished by pretreatment with TRPV1 antagonists capsazepine, BCTC, or AMG9810. Complete Freund's adjuvant (CFA)-induced inflammatory pain in rats significantly increased the expression of Shp-1, TRPV1, and tyrosine-phosphorylated TRPV1, as well as the colocalization of Shp-1 and TRPV1 in DRGs. Intrathecal injection of sodium stibogluconate aggravated CFA-induced inflammatory pain, whereas Shp-1 overexpression in DRG neurons alleviated it. These results suggested that Shp-1 dephosphorylated and inhibited TRPV1 in DRG neurons, contributing to maintain thermal nociceptive thresholds in normal rats, and as a compensatory mechanism, Shp-1 increased in DRGs of rats with CFA-induced inflammatory pain, which was involved in protecting against excessive thermal hyperalgesia.