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Hypothalamic orexin (hypocretin) neurons play crucial roles in arousal control. Their involvement in anesthesia and analgesia remains to be better understood. In order to enhance our view on the neuroanatomy, we systematically mapped the projections of orexin neurons with confocal microscope and light sheet microscope. We specifically expressed optogenetic opsins tagged with fluorescence markers in orexin neurons through adeno-associated viral infection in the mouse brain. The imaging results revealed fine details and novel features of the orexin projections throughout the brain, particularly related to the nuclei regulating arousal and pain. We then optogenetically activated orexin neurons in the lateral hypothalamus to study the effects on anesthesia-related behaviors. cFos staining showed that optogenetic stimulation can activate orexin neurons in the ChR2-mCherry group, but not the control mCherry group (62.86 ± 3.923% vs. 7.9 ± 2.072%; P < 0.0001). In behavior assays, optogenetic stimulation in the ChR2-mCherry group consistently elicited robust arousal from light isoflurane anesthesia (9.429 ± 3.804 s vs. 238.2 ± 17.42 s; P < 0.0001), shortened the emergence time after deep isoflurane anesthesia (109.5 ± 13.59 s vs. 213.8 ± 21.77 s; P = 0.0023), and increased the paw withdrawal latency in a hotplate test (11.45 ± 1.185 s vs. 8.767 ± 0.7775; P = 0.0317). The structural details of orexin fibers established the neuroanatomic basis for studying the role of orexin in anesthesia and analgesia.

Background: This research aimed to examine the global developing patterns in the treatment of diabetic peripheral neuropathy (DPN) using a bibliometric analysis of published literature. Methods: We extracted publication data from papers published between 2014 and 2024 using a specific topic search in the "Web of Science Core Collection" (WoSCC) database. Various metrics, such as the number of papers, citations, authors, countries, institutions, and references, were collected for analysis. To further explore the data, CiteSpace was employed to examine co-citation patterns among authors, identify collaborative efforts between countries and institutions, and uncover emerging trends using burst keywords and reference analysis. Results: The study encompassed 2,488 publications that exhibited an increasing trend in annual output. Notably, the journal PAIN , the United States, the Pfizer institution, and the author Feldman, EvaL emerged as the most prolific contributors to this research domain. The term "placebo-controlled trial" was the most prominent burst keyword from 2014 to 2017, whereas "spinal cord stimulation" held this distinction in the recent 5-year span. Furthermore, the publication titled "Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis-2015" demonstrated the highest burst in terms of references. Conclusion: This study is the first to objectively reveal the current hotspots and trends in DPN treatment. The results indicate that drug therapy remains the primary first-line treatment for DPN and that future research on DPN treatment will likely focus on "spinal cord stimulation" and "pain management." These findings provide valuable insights into DPN treatment. [ABSTRACT FROM AUTHOR]

Aims: Chronic pain is highly associated with anxiety. Electroacupuncture (EA) is effective in relieving pain and anxiety. Currently, little is known about the neural mechanisms underlying the comorbidity of chronic pain and anxiety and the EA mechanism. This study investigated a potential neural circuit underlying the comorbid and EA mechanisms. Methods: Spared nerve injury (SNI) surgery established the chronic neuropathic pain mouse model. The neural circuit was activated or inhibited using the chemogenetic method to explore the relationship between the neural circuit and mechanical allodynia and anxiety‐like behaviors. EA combined with the chemogenetic method was used to explore whether the effects of EA were related to this neural circuit. Results: EA attenuated mechanical allodynia and anxiety‐like behaviors in SNI mice, which may be associated with the activity of CaMKII neurons in the basolateral amygdala (BLA). Inhibition of BLACaMKII‐rACC induced mechanical allodynia and anxiety‐like behaviors in sham mice. Activation of the BLACaMKII‐rACC alleviated neuropathic pain and anxiety‐like behaviors in SNI mice. The analgesic and anxiolytic effects of 2 Hz EA were antagonized by the inhibition of the BLACaMKII‐rACC. Conclusion: BLACaMKII‐rACC mediates mechanical allodynia and anxiety‐like behaviors. The analgesic and anxiolytic effects of 2 Hz EA may be associated with the BLACaMKII‐rACC. [ABSTRACT FROM AUTHOR]

Aims: Negative emotions induced by chronic pain are a serious clinical problem. Electroacupuncture (EA) is a clinically proven safe and effective method to manage pain‐related negative emotions. However, the circuit mechanisms underlying the effect of EA treatment on negative emotions remain unclear. Methods: Plantar injection of complete Freund's adjuvant (CFA) was performed to establish a rat model of chronic inflammatory pain‐induced anxiety‐like behaviors. Adeno‐associated virus (AAV) tracing was used to identify excitatory synaptic transmission from the rostral anterior cingulate cortex (rACC) to the dorsal raphe nucleus (DRN). Employing chemogenetic approaches, we examined the role of the rACC‐DRN circuit in chronic pain‐induced anxiety‐like behaviors and investigated whether EA could reverse chronic pain‐induced dysfunctions of the rACC‐DRN circuit and anxiety‐like behaviors. Results: We found that chemogenetic activation of the rACC‐DRN circuit alleviated CFA‐induced anxiety‐like behaviors, while chemogenetic inhibition of the rACC‐DRN circuit resulted in short‐term CFA‐induced anxiety‐like behaviors. Further research revealed that the development of CFA‐induced anxiety‐like behaviors was attributed to the dysfunction of rACC CaMKII neurons projecting to DRN serotonergic neurons (rACCCaMKII‐DRN5‐HT neurons) but not rACC CaMKII neurons projecting to DRN GABAergic neurons (rACCCaMKII‐DRNGABA neurons). This is supported by the findings that chemogenetic activation of the rACCCaMKII‐DRN5‐HT circuit alleviates anxiety‐like behaviors in rats with chronic pain, whereas neither chemogenetic inhibition nor chemogenetic activation of the rACCCaMKII‐DRNGABA circuit altered CFA chronic pain‐evoked anxiety‐like behaviors in rats. More importantly, we found that EA could reverse chronic pain‐induced changes in the activity of rACC CaMKII neurons and DRN 5‐HTergic neurons and that chemogenetic inhibition of the rACCCaMKII‐DRN5‐HT circuit blocked the therapeutic effects of EA on chronic pain‐induced anxiety‐like behaviors. Conclusions: Our data suggest that the reversal of rACCCaMKII‐DRN5‐HT circuit dysfunction may be a mechanism underlying the therapeutic effect of EA on chronic pain‐induced anxiety‐like behaviors. [ABSTRACT FROM AUTHOR]