In order to investigate whether the effect of Yuxuebi Tablets on the peripheral and central inflammation resolution of mice with inflammatory pain is related to their regulation of G protein-coupled receptor 37(GPR37), an inflammatory pain model was established by injecting complete Freund's adjuvant(CFA) into the paws of mice, with a sham-operated group receiving a similar volume of normal saline. The mice were assigned randomly to the sham-operated group, model group, ibuprofen group(91 mg·kg~(-1)), and low-, medium-, and high-dose groups of Yuxuebi Tablets(60, 120, and 240 mg·kg~(-1)). The drug was administered orally from days 1 to 19 after modeling. Von Frey method and the hot plate test were used to detect mechanical pain thresholds and heat hyperalgesia. The levels of interleukin-10(IL-10) and transforming growth factor-beta(TGF-β) in the spinal cord were quantified using enzyme-linked immunosorbent assay(ELISA), and the mRNA and protein expression of GPR37 in the spinal cord was measured by real-time quantitative reverse transcription PCR(qRT-PCR) and Western blot. Additionally, immunofluorescence was used to detect the expression of macrosialin antigen(CD68), mannose receptor(MRC1 or CD206), and GPR37 in dorsal root ganglia, as well as the expression of calcium-binding adapter molecule 1(IBA1), CD206, and GPR37 in the dorsal horn of the spinal cord. The results showed that compared with those of the sham-operated group, the mechanical pain thresholds and hot withdrawal latency of the model group significantly declined, and the expression of CD68 in the dorsal root ganglia and the expression of IBA1 in the dorsal horn of the spinal cord significantly increased. The expression of CD206 and GPR37 significantly decreased in the dorsal root ganglion and dorsal horn of the spinal cord, and IL-10 and TGF-β levels in the spinal cord were significantly decreased. Compared with those of the model group, the mechanical pain thresholds and hot withdrawal latency of the high-dose group of Yuxuebi Tablets significantly increased, and the expression of CD68 in the dorsal root ganglion and IBA1 in the dorsal horn of the spinal cord significantly decreased. The expression of CD206 and GPR37 in the dorsal root ganglion and dorsal horn of the spinal cord significantly increased, as well as IL-10 and TGF-β levels in the spinal cord. These findings indicated that Yuxuebi Tablets may reduce macrophage(microglial) infiltration and foster M2 macrophage polarization by enhancing GPR37 expression in the dorsal root ganglia and dorsal horn of the spinal cord of CFA-induced mice, so as to improve IL-10 and TGF-β levels, promote resolution of both peripheral and central inflammation, and play analgesic effects.
Inflammation/genetics* ; Pain/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Mice ; Freund's Adjuvant/pharmacology* ; Ibuprofen ; Pain Threshold/drug effects* ; Hyperalgesia/genetics* ; Ganglia, Spinal ; Interleukin-10/genetics* ; Transforming Growth Factor beta/genetics* ; Reverse Transcriptase Polymerase Chain Reaction ; Tablets ; Receptors, G-Protein-Coupled

OBJECTIVE: Acupuncture has demonstrated efficacy as a treatment for fibromyalgia; however, predictors of short- and long-term analgesic response in this population are not well understood. METHODS: This manuscript describes a secondary analysis of a single-center, blinded, sham-controlled, randomized longitudinal acupuncture clinical trial in fibromyalgia. Baseline characterization included pressure pain threshold and pain interference, while residualized change in pain intensity from baseline to follow-up served as the primary outcome measure. Participants were randomized into groups that received verum (n = 36) or sham (n = 29) acupuncture treatment over a 12-week period (18 treatments) and were followed for 37 weeks from the initiation of treatment. RESULTS: Lower pressure pain thresholds at baseline were associated with greater analgesia only in the sham treatment group immediately following treatment, while those with higher pressure pain thresholds had greater analgesia with verum treatment (B = -13.43, P = 0.001). Additionally, greater perceived impact of pain at baseline was predictive of greater short-term analgesia irrespective of treatment. Pressure pain threshold was not found to be predictive of long-term differential treatment response (B = -1.71, P = 0.66). There was a significant difference in the relationship between perceived impact of pain at baseline and subsequent long-term analgesia between groups where those with greater perceived impact of pain displayed improved long-term analgesia for verum acupuncture compared to the sham group (B = -11.37, P = 0.004). CONCLUSION Our results support the use of a self-reported pain outcome in predicting long-term analgesia following acupuncture in fibromyalgia. Please cite this article as: Murphy AE, Arewasikporn A, Taylor-Swanson L, Williams DA, Harris RE. Pressure pain threshold and perceived impact of pain differentially predict short-term and long-term pain reduction following acupuncture in fibromyalgia. J Integr Med. 2025; 23(2): 152-158.
Adult ; Female ; Humans ; Male ; Middle Aged ; Acupuncture Therapy ; Fibromyalgia/therapy* ; Pain Management/methods* ; Pain Measurement/statistics & numerical data* ; Pain Threshold/physiology* ; Pressure ; Treatment Outcome ; Longitudinal Studies

Objective:To explore the trend of hearing changes in infants with GJB2 gene p.V37I mutation at different months. Methods:The subjects were 54 children（108 ears） with p.V37I homozygous or compound heterozygous mutation in GJB2 gene. All the subjects underwent auditory brainstem response, auditory steady-state response, acoustic immittance and other audiological tests. Children were divided into three groups according to their age, 26 cases in group A were ≤3 months old, 17 cases in group B were>3~≤6 months old, and 11 cases in group C were>6 months old. Statistical analysis was performed on the three groups of ABR response threshold, hearing degree, the ASSR average response threshold of four frequencies and the ASSR response thresholds for each frequency of 500, 1 000, 2 000 and 4 000 Hz. Results:Among the 54 cases, 35 were male and 19 were female, with an age rang of 2-27 months and a median age of 4 months. The ABR response threshold of the three groups were ranked from low to high as group A, group B and group C, and the difference was statistically significant（P<0.05）. The ABR response thresholds of the three groups were ranked from low to high as group A, group B, and group C. The comparison between groups showed that the ABR response thresholds of group C was higher than that of group A（P=0.006）. The proportion of confirmed hearing loss in the three groups was 34.61%, 50.00% and 63.64%, respectively, and the difference of hearing level among the three groups was statistically significant（P<0.05）. The comparison between groups showed that the difference between group A and group C was statistically significant（P=0.012）, normal hearing accounted for the highest proportion in group A（65.39%）, while mild hearing loss accounted for the highest proportion in group C（45.46%）. The ASSR average response thresholds of the four frequencies in the three groups were ranked from low to high as group A, group B and group C, and the difference is statistically significant（P<0.05）. The comparison between groups showed that response ASSR thresholds of group C was higher than that of group A（P=0.002）. Response thresholds of ASSR in each frequency in the three groups were all ranked from low to high as in group A, group B and group C, and the differences were statistically significant（P<0.05）. Compared with each other between groups, response ASSR thresholds of group C was higher than those of group A（P=0.003） and group B（P=0.015） at 500 Hz, while response ASSR thresholds of group C was higher than group A at 1 000 Hz（P=0.010） and 2 000 Hz（P<0.001）, and there was no statistical difference at 4 000 Hz. Conclusion:The incidence of hearing loss in GJB2 gene p.V37I mutation increased with age, and the degree of hearing loss increased, the hearing progression was mainly 500, 1 000 and 2 000 Hz suggesting regular follow-up and alert to hearing changes.
Humans ; Connexin 26 ; Male ; Female ; Infant ; Child, Preschool ; Mutation ; Evoked Potentials, Auditory, Brain Stem ; Connexins/genetics* ; Auditory Threshold ; Hearing/genetics* ; Hearing Loss/genetics*

Objective:To evaluate the effectiveness of amplification intervention with hearing aids for restoring binaural auditory function in patients with unilateral moderate to severe sensorineural hearing loss. Methods:This study selected 30 patients with normal hearing in one ear and moderate to severe sensorineural hearing loss in the other ear. They were fitted with hearing aids for the worse ear and underwent more than half a year and one year of adaptation training. The Chinese translation of the Twelve-item version of SSQ（C-SSQ12）, angle identification test, speech recognition score（SRS） at different signal-to-noise ratios（SNR=5 and SNR=10） and audiometric thresholds were used to compare the results before and after hearing aid use to evaluate the effectiveness of the unilateral hearing loss intervention. Results:The results of the audiometric thresholds, C-SSQ12 scores, angle identification test, and SRS at SNR=5 and SNR=10 in the worse ear of the unilateral hearing loss patients after hearing aid use were all statistically significant compared to before hearing aid use（P<0.01）. Conclusion:Amplification intervention with hearing aids has significant effects on restoring binaural auditory function in patients with unilateral moderate to severe sensorineural hearing loss.
Humans ; Hearing Aids ; Hearing Loss, Unilateral/therapy* ; Middle Aged ; Hearing Loss, Sensorineural/rehabilitation* ; Adult ; Female ; Male ; Auditory Threshold ; Young Adult ; Aged

Objective:To explore the hearing changes of children with different genotypes of SLC26A4 with enlarged vestibular aqueduct（EVA） using the linear mixed effect model（LMM）, providing evidence for the risk prediction of progressive hearing loss. Methods:A total of 48 children with EVA diagnosed in our hospital from January 2017 to January 2024. All subjects underwent two or more auditory tests. According to the results of deafness gene screening and sequencing, the genotypes are divided into: type A: homozygous mutation of c. 919-2A>G, type B: compound heterozygous or heterozygous mutation containing c. 919-2A>G, and type C: no mutation site of c. 919-2A>G of SLC26A4 gene. LMM was used to analyze the hearing thresholds change of 500 Hz, 1 000 Hz, 2 000 Hz, 4 000 Hz and the average in children with different genotypes with age. Results:A total of 92 ears, 314 audiograms of 48 children were included, the median number of audiograms was 3, the median age of initial diagnosis was 4 months, and the median follow-up time was 13 months. According to LMM, the standard deviation of random effects between patients and ears was large. There was no significant difference in hearing thresholds of different frequencies and the average in genotype A, genotype B, and genotype C, indicating that genotype had no effect on hearing threshold. There is an interaction between age and genotype. Taking genotype C as the reference, children with genotype B had the lowest increase in 500 Hz, 1000 Hz, and the average hearing threshold, followed by type A. Conclusion:EVA children exhibit substantial inter-individual/ear hearing threshold variability. Low-frequency thresholds progress slower than high frequencies. Genotype modulates progression rates, with wild-type（Type C） demonstrating fastest deterioration, supporting personalized auditory monitoring strategies.
Humans ; Vestibular Aqueduct/abnormalities* ; Genotype ; Sulfate Transporters ; Mutation ; Auditory Threshold ; Hearing Loss, Sensorineural/genetics* ; Male ; Female ; Child ; Child, Preschool ; Hearing Loss/genetics* ; Hearing Tests ; Linear Models ; Infant

Objective:To explore the application value of P1 response threshold of cortical auditory evoked potential（CAEP） in evaluating the rehabilitation effect of cochlear implant in young children. Methods:Thirty-three young children after cochlear implantation were divided into groups according to hearing age: Group A（hearing age 1-<2 years old） 10 people; Group B（hearing age 2-<3 years old） 13 people; Group C（hearing age 3-<4 years old） 10 people. The subjective assessment was carried out using the assessment tool for hearing-impaired children- "Criteria and Methods for assessing Auditory and language ability of hearing-impaired children" and objective electrophysiological examination was carried out using CAEP to evaluate the rehabilitation effect. SPSS 25.0 software was used for statistical analysis. Results:The results of subjective assessment of auditory ability and language ability in each group showed an increasing trend with the increase of auditory age. In this study, the P1 response threshold of CAEP in CI implanted children had a significant positive correlation with the 2 kHz hearing threshold after intervention, and the P1 response threshold of CAEP was negatively correlated with many items in subjective auditory ability and language ability assessment. Conclusion:The P1 response threshold of CAEP has a stable correlation with the results of speech audiometry, which can effectively and objectively evaluate the postoperative rehabilitation effect of young children with cochlear implantation.
Humans ; Child, Preschool ; Infant ; Male ; Female ; Evoked Potentials, Auditory ; Cochlear Implantation/rehabilitation* ; Cochlear Implants ; Auditory Threshold

Objective:This study aims to analyze the threshold changes in distortion product otoacoustic emissions（DPOAE） and auditory brainstem response（ABR） in adult Otof-/- mice before and after gene therapy, evaluating its effectiveness and exploring methods for assessing hearing recovery post-treatment. Methods:At the age of 4 weeks, adult Otof-/- mice received an inner ear injection of a therapeutic agent containing intein-mediated recombination of the OTOF gene, delivered via dual AAV vectors through the round window membrane（RWM）. Immunofluorescence staining assessed the proportion of inner ear hair cells with restored otoferlin expression and the number of synapses.Statistical analysis was performed to compare the DPOAE and ABR thresholds before and after the treatment. Results:AAV-PHP. eB demonstrates high transduction efficiency in inner ear hair cells. The therapeutic regimen corrected hearing loss in adult Otof-/- mice without impacting auditory function in wild-type mice. The changes in DPOAE and ABR thresholds after gene therapy are significantly correlated at 16 kHz. Post-treatment,a slight increase in DPOAE was observeds,followed by a recovery trend at 2 months post-treatment. Conclusion:Gene therapy significantly restored hearing in adult Otof-/- mice, though the surgical delivery may cause transient hearing damage. Precise and gentle surgical techniques are essential to maximize gene therapy's efficacy.
Mice ; Animals ; Otoacoustic Emissions, Spontaneous/physiology* ; Hearing/physiology* ; Ear, Inner ; Hearing Loss/therapy* ; Genetic Therapy ; Auditory Threshold/physiology* ; Evoked Potentials, Auditory, Brain Stem/physiology* ; Membrane Proteins

Sleep deprivation has been shown to exacerbate pain sensitivity and may contribute to the onset of chronic pain, yet the precise neural mechanisms underlying this association remain elusive. In our study, we explored the contribution of cholinergic neurons within the medial habenula (MHb) to hyperalgesia induced by sleep deprivation in rats. Our findings indicate that the activity of MHb cholinergic neurons diminishes during sleep deprivation and that chemogenetic stimulation of these neurons can mitigate the results. Interestingly, we did not find a direct response of MHb cholinergic neurons to pain stimulation. Further investigation identified the interpeduncular nucleus (IPN) and the paraventricular nucleus of the thalamus (PVT) as key players in the pro-nociceptive effect of sleep deprivation. Stimulating the pathways connecting the MHb to the IPN and PVT alleviated the hyperalgesia. These results underscore the important role of MHb cholinergic neurons in modulating pain sensitivity linked to sleep deprivation, highlighting potential neural targets for mitigating sleep deprivation-induced hyperalgesia.
Animals ; Habenula/physiology* ; Sleep Deprivation/physiopathology* ; Cholinergic Neurons/physiology* ; Male ; Hyperalgesia/physiopathology* ; Rats, Sprague-Dawley ; Rats ; Interpeduncular Nucleus/physiology* ; Pain Threshold/physiology* ; Midline Thalamic Nuclei/physiology* ; Neural Pathways/physiopathology*

OBJECTIVES: Pelvic floor sensory training is commonly used in clinical practice for the treatment of stress urinary incontinence (SUI); however, there is a lack of comparative studies evaluating pelvic floor sensation between women with SUI and healthy controls. Additionally, normative data for two-point discrimination thresholds in the female pelvic floor region remain scarce. This study aims to compare the results of 4 sensory tests in the pelvic floor region between women with mild SUI and healthy women, in order to provide reference values for two-point discrimination thresholds in this area. METHODS: From April 1 to October 30, 2023, 108 healthy women [(32.5±3.6) years] and 90 women with mild SUI [(32.9±3.3) years] were recruited from the Third Xiangya Hospital, Central South University. Participants underwent 4 sensory tests in the pelvic floor region: Two-dot discrimination, weight perception, shape recognition, and 9-grid localization. The results were compared between the 2 groups. RESULTS: Compared with healthy women, those with mild SUI had lower sensitivity and higher thresholds in 2-dot discrimination tests in the pelvic floor region (all P<0.001). No significant differences were found between groups in weight perception, shape recognition, or grid localization tests (P>0.05). CONCLUSIONS Women with mild stress urinary incontinence have impaired two-point discrimination ability in the pelvic floor region.
Humans ; Female ; Urinary Incontinence, Stress/physiopathology* ; Pelvic Floor/physiopathology* ; Adult ; Sensory Thresholds/physiology*

Objective:To investigate the application value of NB CE-Chirp ASSR in the assessment of hearing threshold in children with hearing impairment. Methods:The hearing test results of 44 children with sensorineural hearing loss（88 ears） diagnosed in Shanghai Children's Hospital from January 2023 to December 2023 were retrospectively studied, including 19 ears in mild hearing loss group, 26 ears in moderate group, 20 ears in severe group and 23 ears in extremely severe group. Correlations between auditory brainstem response（ABR） thresholds, pure tone audiometry（PTA） thresholds and NB CE-Chirp ASSR response thresholds in different hearing loss groups were analyzed. Results:The threshold difference between ABR and NB CE-Chirp ASSR（2 000-4 000 Hz） was between 0.50-4.08 dB in different degrees of hearing loss group. There was a significant correlation between NB CE-Chirp ASSR and ABR response threshold in each group（P<0.001）, and the correlation coefficients of mild, severe and extremely severe groups were all greater than 0.8, showing a strong correlation. The average threshold difference between PTA and NB CE-Chirp ASSR in each group was between 1.88-3.91 dB. The correlation coefficients were all greater than 0.8, showing a strong correlation. The difference between PTA and NB CE-Chirp ASSR response threshold at 500, 1 000, 2 000 and 4 000 Hz in each groupwas between 0.25-3.84 dB. With the increase of frequency, the correlation coefficient between PTA and NB CE-Chirp ASSR response threshold showed an upward trend. The frequency with the highest coefficient was 4 000 Hz, and the r values were all greater than 0.9, followed by 2 000 Hz, and the correlation coefficient was relatively low at 500 Hz. In the extremely severe group, each frequency coefficient was greater than 0.7, showing a strong correlation. Conclusion:NB CE-Chirp ASSR has good frequency specificity and can reliably assess hearing thresholds in hearing-impaired children.
Humans ; Auditory Threshold ; Child ; Retrospective Studies ; Female ; Male ; Audiometry, Pure-Tone/methods* ; Evoked Potentials, Auditory, Brain Stem ; Child, Preschool ; Hearing Loss, Sensorineural/physiopathology* ; Adolescent