Circadian changes of autonomic function in patients with zoster-associated pain: A heart rate variability analysis.

OBJECTIVE: To investigate the circadian changes of the autonomic function in patients with zoster-associated pain (ZAP). METHODS: A total of 37 patients with ZAP from April 2022 to October 2022 were enrolled as the observation group, and 37 normal volunteers at the same time were selected as the control group. All participants were required to wear a 24-h Holter, which was used to compare the heart rate variability (HRV) between the two groups. HRV analysis involved time- and frequency-domain parameters. RESULTS: There was no statistically significant difference in general information between two groups. Patients with ZAP had an increased mean heart rate and decreased the standard deviation of normal-to-normal (SDNN) R-R interval, the root mean square of the differences (RMSSD) in successive RR interval, low frequency (LF), and high frequency (HF) compared with control groups in all periods (p < .05). The ratio of LF/HF between two groups had no significant difference (p = .245). SDNN had no significant difference between day and night in the control group (p > .05), whereas SDNN of ZAP patients in night period was reduced than that in day period (p < .001). The level of RMSSD during the day was lower than those at night in the control group (p < .05), whereas no significant difference of RMSSD between two periods was observed in patients with ZAP (p > .05). CONCLUSION: The results of this study indicated that ZAP contributes to the decline of autonomic nervous system (ANS) function, especially parasympathetic components. The patients with ZAP lost parasympathetic advantage and had a worse ANS during the night.

Glutamatergic neurons in the paraventricular nucleus of the hypothalamus participate in the regulation of visceral pain induced by pancreatic cancer in mice.

Background: Visceral pain induced by pancreatic cancer seriously affects patients' quality of life, and there is no effective treatment, because the mechanism of its neural circuit is unknown. Therefore, the aim of this study is to explore the main neural circuit mechanism regulating visceral pain induced by pancreatic cancer in mice. Methods: The mouse model of pancreatic cancer visceral pain was established on C57BL/6N mice by pancreatic injection of mPAKPC-luc cells. Abdominal mechanical hyperalgesia and hunch score were performed to assess visceral pain; the pseudorabies virus (PRV) was used to identify the brain regions innervating the pancreas; the c-fos co-labeling method was used to ascertain the types of activated neurons; in vitro electrophysiological patch-clamp technique was used to record the electrophysiological activity of specific neurons; the calcium imaging technique was used to determine the calcium activity of specific neurons; specific neuron destruction and chemogenetics methods were used to explore whether specific neurons were involved in visceral pain induced by pancreatic cancer. Results: The PRV injected into the pancreas was detected in the paraventricular nucleus of the hypothalamus (PVN). Immunofluorescence staining showed that the majority of c-fos were co-labeled with glutamatergic neurons in the PVN. In vitro electrophysiological results showed that the firing frequency of glutamatergic neurons in the PVN was increased. The calcium imaging results showed that the calcium activity of glutamatergic neurons in the PVN was enhanced. Both specific destruction of glutamatergic neurons and chemogenetics inhibition of glutamatergic neurons in the PVN alleviated visceral pain induced by pancreatic cancer. Conclusions: Glutamatergic neurons in the PVN participate in the regulation of visceral pain induced by pancreatic cancer in mice, providing new insights for the discovery of effective targets for the treatment of pancreatic cancer visceral pain.

Neuroinflammation in the paraventricular nucleus of the hypothalamus precipitates visceral pain induced by pancreatic cancer in mice.

Background: Given the pivotal role of neuroinflammation in chronic pain and that the paraventricular nucleus of the hypothalamus (PVN) is a crucial brain region involved in visceral pain regulation, we sought to investigate whether the targeted modulation of microglia and astrocytes in the PVN could ameliorate pancreatic cancer-induced visceral pain (PCVP) in mice. Methods: Using a mouse model of PCVP, achieved by tumor cell injection at the head of the pancreas, we measure the number of glial cells, and at the same time we employed minocycline to inhibit microglia and chemogenetic methods to suppress astrocytes in order to investigate the respective roles of microglia and astrocytes within the PVN in PCVP. Results: Mice exhibited visceral pain at 12, 15 and 18 days post-tumor cell injection. We observed a significant increase in the population of both microglia and astrocytes. Inhibition of microglial activity through minocycline microinjection into the PVN resulted in alleviation of visceral pain within 30 and 60 min. Similarly, chemogenetic inhibition of astrocyte function at 14 and 21 days post-injection also led to relief from visceral pain. Conclusions: This study found that PVN microglia and astrocytes were involved in regulating PCVP. Our results suggest that targeting glia may be a potential approach for alleviating visceral pain in patients with pancreatic cancer.

Inhibition of GABAergic neurons in the paraventricular nucleus of the hypothalamus precipitates visceral pain induced by pancreatic cancer in mice.

Background: For patients with pancreatic cancer, visceral pain is a debilitating symptom that significantly compromises their quality of life. Unfortunately, the lack of effective treatment options can be attributed to our limited understanding of the neural circuitry underlying this phenomenon. The primary objective of this study is to elucidate the fundamental mechanisms governing visceral pain induced by pancreatic cancer in murine models. Methods: A mouse model of pancreatic cancer visceral pain was established in C57BL/6N mice through the intrapancreatic injection of mPAKPC-luc cells. Abdominal mechanical hyperalgesia and hunch score were employed to evaluate visceral pain, whereas the in vitro electrophysiological patch-clamp technique was utilized to record the electrophysiological activity of GABAergic neurons. Specific neuron ablation and chemogenetics methods were employed to investigate the involvement of GABAergic neurons in pancreatic cancer-induced visceral pain. Results: In vitro electrophysiological results showed that the firing frequency of GABAergic neurons in the paraventricular nucleus of the hypothalamus (PVN) was decreased. Specific destruction of GABAergic neurons in the PVN exacerbated visceral pain induced by pancreatic cancer. Chemogenetics activation of GABAergic neurons in the PVN alleviated visceral pain induced by pancreatic cancer. Conclusions: GABAergic neurons located in PVN play a crucial role in precipitating visceral pain induced by pancreatic cancer in mice, thereby offering novel insights for identifying effective targets to treat pancreatic cancer-related visceral pain.

Efficacy and Safety of Chuanxiong Qingnao Granule in Patients with Migraine: A Randomized, Double-Blind, Placebo-Controlled Trial.

OBJECTIVE: To evaluate the efficacy and safety of Chuanxiong Qingnao Granule (CQG) to treat migraine. METHOD: This study was a randomized, double-blind, placebo-controlled trial. All migraineurs were recruited and randomly assigned into a treatment group treated with CQG and a control group treated with a placebo. The whole research process included a 4-week baseline, 12-week intervention, and 12-week follow-up. The primary outcome was responder rate, defined as the percentage of migraineurs with 50% or more reduction in the frequency of migraine attack during treatment and posttreatment period compared with the baseline. The secondary outcomes were the number of migraine days, migraine attack frequency, visual analogue scale (VAS), Fatigue Severity Scale (FSS), Hamilton Depression Scale (HAMD), and Migraine Disability Assessment (MIDAS). RESULTS: A total of 346 migraineurs completed the research and were included in the intention-treatment analyses. The response rates differed significantly between the treatment group and the control group (71.5% vs. 12.1% at week 12 and 83.1% vs. 3.4% at week 24). Attack frequency, days of headache attack, VAS, FSS, HAMD, and MIDAS decreased at week 12 in both groups with more reduction in the treatment group (P < 0.001). No severe adverse events were observed in this trial. CONCLUSION: Chuanxiong Qingnao Granule can significantly improve headache symptoms in patients with migraine while improving disability, fatigue, and depression with a good safety profile.

Predicting Postherpetic Neuralgia in Patients with Herpes Zoster by Machine Learning: A Retrospective Study.

INTRODUCTION: Postherpetic neuralgia (PHN) is a neuropathic pain secondary to shingles. Studies have shown that early pain intervention can reduce the incidence or intensity of PHN. The aim of this study was to predict whether a patient with acute herpetic neuralgia will develop PHN and to help clinicians make better decisions. METHOD: Five hundred two patients with shingles were reviewed and classified according to whether they had PHN. The risk factors associated with PHN were determined by univariate analysis. Logistic regression and random forest algorithms were used to do machine learning, and then the prediction accuracies of the two algorithms were compared, choosing the superior one to predict the next 60 new cases. RESULTS: Age, NRS score, rash site, Charlson comorbidity index (CCI) score, antiviral therapy and immunosuppression were found related to the occurrence of PHN. The NRS score was the most closely related factor with an importance of 0.31. As for accuracy, the random forest was 96.24%, better than that of logistic regression in which the accuracy was 92.83%. Then, the random forest model was used to predict 60 newly diagnosed patients with herpes zoster, and the accuracy rate was 88.33% with a 95% confidence interval (CI) of 77.43-95.18%. CONCLUSIONS: This study provides an idea and a method in which, by analyzing the data of previous cases, we can develop a predictive model to predict whether patients with shingles will develop PHN.

Patient and economic burdens of postherpetic neuralgia in China.

BACKGROUND: Little is known about the patient-reported and economic burdens of postherpetic neuralgia (PHN) among China's urban population. METHODS: This noninterventional study was conducted among adults ≥40 years with PHN who were seeking medical care at eight urban hospitals in China. At one study site, patients completed a questionnaire evaluating the patient-reported disease burden (N=185). The questionnaire consisted of validated patient-reported outcomes including the Brief Pain Inventory (BPI), 5-dimension, 3-level EuroQol (EQ-5D-3L), Medical Outcomes Study Sleep Scale, and Work Productivity and Activity Impairment Questionnaire for Specific Health Problems. Questions on non-pharmacologic therapy and out-of-pocket (OOP) expenses were also included. At all study sites, physicians (N=100) completed a structured review of patient charts (N=828), which was used to derive health care resource utilization and associated costs from the societal perspective. Annual costs in Chinese Yuan Renminbi (RMB) for the year 2016 were converted to US dollars (US$). RESULTS: Patients (N=185, mean age 63.0 years, 53.5% female) reported pain of moderate severity (mean BPI score 4.6); poor sleep quantity (average of 5.3 hrs per night) and quality; and poorer health status on the EQ-5D-3L relative to the general Chinese population. Respondents also reported average annual OOP costs of RMB 16,873 (US$2541) per patient, mainly for prescription PHN medications (RMB 8990 [US$1354]). Substantial work impairment among employed individuals resulted in annual indirect costs of RMB 28,025 (US$4221). In the chart review, physicians reported that patients (N=828) had substantial health resource utilization, especially office visits; 98% had all-cause and 95% had PHN-related office visits. Total annual direct medical costs were RMB 10,002 (US$1507), mostly driven by hospitalizations (RMB 8781 [US$1323]). CONCLUSION: In urban China, PHN is associated with a patient-reported burden, affecting sleep, quality-of-life, and daily activities including work impairment, and an economic burden resulting from direct medical costs and indirect costs due to lost productivity. These burdens suggest the need for appropriate prevention and management of PHN.

Peripheral nerve field stimulation to the preauricular area for intractable chronic migraine: a case report.

Objective: To report a successful attempt of peripheral nerve field stimulation (PNFS) in preauricular area to treat refractory chronic migraine (CM). This article focuses on novel utilization of PNFS and discusses its existing issues. Case report: A 35-year-old woman diagnosed with CM complained about a 2-year history of severe pain at the occipitocervical and left auriculotemporal area, sometimes bilaterally, which did not benefit from conventional medical therapy. After failed attempts of occipital nerve stimulation and PNFS at the retroauricular area, we used exploratory PNFS at the preauricular area, which to our knowledge is the first reported case in literature, to such an area in refractory CM. The patient experienced satisfactory pain relief and obvious improvement in quality of life. And the amelioration on the severity of pain was validated by reduced scores (from 9 to 2) on the numerical rating scale. The clinical effects continued in the next 2-year follow-up after the implantation, without adverse events. Conclusion: PNFS is a promising and safe neuromodulation therapy for refractory CM. Facial areas like preauricular region are applicable for lead implantation. Nevertheless, the underlying mechanisms are still unverified, and there is still a lack of standardized operation guides of PNFS. Large-scale randomized clinical trials should be conducted to further validate these findings.

Proportion of neuropathic pain in the back region in chronic low back pain patients -a multicenter investigation.

Neuropathy can contribute to low back pain (LBP) in the region of the back. Our study investigated the proportion of neuropathic pain (NP) in low back region in chronic LBP patients from multicenter and clinics in China and identified associated factors. Assessment was made using a questionnaire and the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS, only tested in low back region), as well as Quantitative Sensory Testing (QST, merely applied to the low back region), the Hospital Anxiety and Depression Scale (HADS) and the Oswestry Disability Index (ODI). Our questionnaire collected demographic information, behavioral habits and medical records. 2116 outpatients over 18 years old complaining of LBP lasting more than 3 months were enrolled in this study. The NP proportion in low back region in chronic LBP patients was 2.8%. Multivariable logistic regression analysis showed that histories of lumbar surgery, abdominal or pelvic surgery, and drinking alcohol were independent positive predictors for LBP of predominantly neuropathic origin (LBNPO), while history of low back sprain and frequently carrying weight as independent negative predictor. Using these parameters may help the identification of patients with chronic LBP likely to develop NP leading to improved treatment outcomes.

Postmarketing surveillance study of OxyContin tablets for relieving moderate to severe postherpetic neuralgia pain.

OBJECTIVE: To evaluate the efficacy and safety of OxyContin tablets(controlled-release oxycodone hydrochloride: 5, 10, 20, and 40 mg) in relieving moderate to severe postherpetic neuralgia (PHN) pain. METHOD: A multicenter, open-label, prospective, self-controlled clinical observation. RESULTS: Pain was relieved in 17.3% of patients within 30 min and in 94.1% patients within 1 h after drug administration. OxyContin tablets showed good clinical efficacy in relieving both moderate and severe PHN pain. Response rate reached 98.4% at the end of the 8th week of treatment. After the 1st week of treatment, stable pain relief was achieved, and pain scores on a Visual Analogue Scale decreased dramatically in most patients. During treatment with controlled-release OxyContin tablets, the use of concomitant medications was significantly decreased. Some patients developed adverse drug reactions (ADRs) in the 1st week, which decreased significantly during the following weeks of treatment. Nausea (18.1%) was the most commonly reported ADR, followed by constipation (10.1%) and dizziness (10.1%). A number of ADRs disappeared during treatment. CONCLUSION: Controlled-release OxyContin tablets demonstrated fast onset of PHN pain control, superior efficacy in relieving both moderate and severe PHN pain, and a good safety profile.

[Randomized controlled trials of acupuncture at Tiaokou (ST 38) for treatment of periarthritis of shoulder].

OBJECTIVE: To study the basic therapeutic function of Tiaokou (ST 38). METHODS: According to clinically multi-central randomized controlled and single-blind test principle, 257 cases of periarthritis of shoulder were divided into two groups, a test group (n = 124) treated with oral anti-inflammatory analgesic medicine combined with acupuncture at Tiaokou (ST 38), and a control group (n = 133) treated with oral anti-inflammatory analgesic medicine. Their therapeutic effects were compared. RESULTS: The total effective rate for stopping pain was 96.0% in the test group and 91.7% in the control group with a very significant difference between the two groups (P< 0.01). And the total effective rate for improvement of shoulder activity was 86.3% in the test group and 59.4% in the control group with a very significant difference between the two groups (P<0.01). CONCLUSION: Oral anti-inflammatory analgesic medicine combined with acupuncture has obvious therapeutic effect on periarthritis of shoulder, which is better than that of simple oral anti-inflammatory analgesic medicine.