Pain Research and Management

Purpose. Two-sample Mendelian randomization (MR) was conducted to assess the causal relationship between angina pectoris and gout. Material and Methods. Based on genome-wide association studies, single nucleotide polymorphisms (SNPs) that were closely associated with gout were selected from the UK Biobank–Neale Lab (ukb-a-107) as genetic instrumental variables. Considering that gout is characterized by elevated blood uric acid levels, SNPs related to blood uric acid levels were screened from BioBank Japan (bbj-a-57) as auxiliary gene instrumental variables. SNPs closely associated with angina pectoris onset were screened from the FINN dataset (finn-b-I9_ANGINA) as outcome variables. Two-sample MR was conducted, with inverse variance weighting (IVW) of the random effects model as the primary result, along with the weighted median method (WME) and the MR-Egger regression method. To further confirm the causal relationship between angina and gout incidence, a meta-analysis was conducted on the IVW results of the ukb-a-107 and bbj-a-57. Results. The odds ratios and 95% confidence intervals of the IVW, WME, and MR-Egger results of ukb-a-107 were (OR = 33.72; 95% CI: 2.07∼550.38), (OR = 57.94; 95% CI: 2.75∼1219.82), and (OR = 96.38; 95% CI: 0.6∼15556.93), respectively. The values of IVW and WME were 0.014 and 0.014 (both <0.05), respectively, indicating that the development of angina pectoris was significantly associated with the incidence of gout. The odds ratios and 95% confidence intervals of the IVW, WME, and MR-Egger about bbj-a-57 were (OR = 1.20; 95% CI: 1.07∼1.34), (OR = 1.19; 95% CI: 1.02∼1.38), and (OR = 1.30; 95% CI; 1.06∼1.60), respectively. The values of IVW, WME and MR-Egger were 0.001, 0.027 and 0.017 (all <0.05), respectively, indicating a significant correlation between angina and blood uric acid levels. Scatter plots of ukb-a-107 and bbj-a-57 showed that the causal association estimates of the IVW, MR-Egger, and weighted median methods were similar and that the MR results were accurate. Funnel plots and the MR-Egger intercept of ukb-a-107 and bbj-a-57 showed the absence of horizontal pleiotropy. The leave-out sensitivity analysis results of ukb-a-107 and bbj-a-57 are stable. The meta-analysis of IVW results for ukb-a-107 and bbj-a-57 showed (OR = 1.20; 95% CI: 1.07–1.34, ), confirming that gout characterized by high blood uric acid levels significantly increases the risk of angina attacks. Conclusions. This MR study found a clear causal relationship between angina pectoris and gout, which increases the risk of angina pectoris.

Objective. To assess the effectiveness of myofascial release (MFR) techniques on the intensity of headache pain and associated disability in patients with tension-type headache (TTH), cervicogenic headache (CGH), or migraine. Design. A systematic review and meta-analysis. Methods. Eight databases were searched on September 15, 2023, including PubMed, Scopus, Web of Science, CINAHL, Cochrane Library, Embase, CNKI, and Wanfang Database. The risk of bias was evaluated utilizing the Cochrane Risk of Bias 2 (RoB 2) tool. Results. Pooled results showed that MFR intervention significantly reduces pain intensity [SMD = −2.01, 95% CI (−2.98, −1.03),  = 90%, ] and improves disability [SMD = −1.3, 95% CI (−1.82, −0.79),  = 74%, ]. Subgroup analysis based on the type of headache revealed significant reductions in pain intensity for CGH [SMD = −2.01, 95% CI (−2.73, −1.29),  = 63%, ], TTH [SMD = −0.86, 95% CI (−1.52, −0.20),  = 50%, ] and migraine [SMD = −6.52, 95% CI (−8.15, −4.89), ] and in disability for CGH [SMD = −1.45, 95% CI (−2.07, −0.83),  = 0%, ]; TTH [SMD = −0.98, 95% CI (−1.32, −0.65),  = 0%, ] but not migraine [SMD = −2.44, 95% CI (−6.04, 1.16),  = 97%, ]. Conclusion. The meta-analysis results indicate that MFR intervention can significantly alleviate pain and disability in TTH and CGH. For migraine, however, the results were inconsistent, and there was only moderate quality evidence of disability improvement for TTH and CGH. In contrast, the quality of other evidence was low or very low.

Background. Patients undergoing breast surgery are at risk of severe postoperative pain. Several opioid-sparing strategies exist to alleviate this condition. Regional anesthesia has long been a part of perioperative pain management for these patients. Aim. This randomized study examined the benefits of interpectoral and pectoserratus plane block (IPP/PSP), also known as pectoralis nerve plain block, compared with advanced local anesthetic infiltration. Methods. We analyzed 57 patients undergoing partial mastectomy with sentinel node dissection. They received either an ultrasound-guided IPP/PSP block performed preoperatively by an anesthetist or local anesthetic infiltration performed by the surgeon before and during the surgery. Results. Pain measured with the numerical rating scale (NRS) indicated no statistically significant difference between the groups (IPP/PSP 1.67 vs. infiltration 1.97; value 0.578). Intraoperative use of fentanyl was significantly lower in the IPP/PSP group (0.18 mg vs 0.21 mg; value 0.041). There was no statistically significant difference in the length of stay in the PACU (166 min vs 175 min; value 0.51). There were no differences in reported postoperative nausea and vomiting (PONV) between the groups. The difference in postoperative use of oxycodone in the PACU ( value 0.7) and the use of oxycodone within 24 hours postoperatively ( value 0.87) was not statistically significant. Conclusions. Our study showed decreased intraoperative opioid use in the IPP/PSP group and no difference in postoperative pain scores up to 24 hours. Both groups reported low postoperative pain scores. This trial is registered with NCT04824599.

Background. Lumbar spinal stenosis (LSS) causes low back pain, leg pain, numbness in the leg, and neurogenic intermittent claudication. Epidural steroid injection (ESI) has been used for treating spinal stenosis symptoms. We hypothesized that dural pulsation was variable for lumbar spinal stenosis. In cases of the presence of dural pulsation, the pain relief after the ESI was better than in the absence of dural pulsation. This study aimed at investigating the relationships between the presence or absence of spinal dural pulsations and the efficacy of ESI. Methods. A total of 71 patients were enrolled in this prospective study. Prior to the ESI, the dural pulsation was measured using a 5-1 MHz array ultrasound transducer. The visual analogue scale (VAS) score was measured pre-ESI and 2 weeks post-ESI and 4 weeks post-ESI. At 4 weeks post-ESI, dural pulsation was rechecked. Results. The VAS scores improved after the ESI procedure regardless of the presence or absence of dural pulsation. There was a correlation between the pulsation of the dura and post-ESI VAS scores. However, VAS was not significantly different for different grades of stenosis. Conclusion. The ESI was effective in patients with spinal stenosis in short-term follow-up. Dural pulsation of the spinal cord was a positive predictive factor for the ESI effect, but the grade of spinal stenosis severity had no effect on the effectiveness of ESI.

Objectives. Knee osteoarthritis (KOA) pain is caused by nociceptors, which are actually sensory nerve fiber endings that can detect stimuli to produce and transmit pain signals, and high levels of NGF in synovial tissue led to peripheral hyperalgesia in KOA. The purpose of this study is to investigate how sensory nerve fibers respond to the NGF/TrKA signal pathway and mediate the peripheral hyperalgesia in KOA rats. Methods. Forty SD male rats were randomly divided into 4 groups: normal, KOA, KOA + NGF, and KOA + siRNA TrKA. KOA model rats were induced by anterior cruciate ligament transection (ACLT). Mechanical and cold withdrawal thresholds (MWT and CWT) were measured 4 times in each group. The synovial tissues were harvested on day 28, and the expressions of NGF, TrKA, TRPV1, IL-1β, and PGP9.5 were determined using western blot, qPCR, and immunofluorescence staining. The primary rat fibroblast-like synoviocytes (FLSs) and DRG cells were divided into 4 groups as in vivo. The expressions of NGF, TrKA, TRPV1, and CGRP in vitro were determined using western blot and qPCR. Results. KOA and intra-articular injection with NGF protein increased both mRNA and protein levels, not only TRPV1, PGP 9.5, and IL-1β in the synovial tissue, but also TRPV1, PGP 9.5, and S100 in the DRG tissue, while above changes were partly reversed after siRNA TrKA intervention. Besides, siRNA TrKA could improve peripheral hyperalgesia and decreased the TRPV1 positive nerve fiber innervation in synovial tissue. The results in vitro were consistent with those in vivo. Conclusion. This study showed the activation of the NGF/TrKA signaling pathway in KOA promoted the release of pain mediators, increased the innervation of sensory nerve fibers in the synovium, and worsened peripheral hyperalgesia. It also showed increased TRPV1 positive sensory innervation in KOA was mediated by NGF/TrKA signaling and exacerbated peripheral hyperalgesia.

Background. Treatment of persistent spinal pain syndrome (PSPS) is challenging. Chronic pain associated with PSPS can lead to an impaired ability to work. Objective. To obtain information on whether receiving a disability pension (DP) affects pain and pain treatments in retiring working-age PSPS patients. Neuropathic pain medication and antidepressant use were considered as an indicator of neuropathic pain. Methods. The study group comprised 129 consecutive PSPS patients with spinal cord stimulation (SCS) devices implanted at Kuopio University Hospital Neurosurgery between January 1, 1996, and December 31, 2014. Purchase data of gabapentinoids, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors from January 1995 to March 2016, as well as the data on working ability, were retrieved from national registries. Results. The data showed that 28 of 129 (21.7%) SCS permanent patients had a DP, and 27 had a sufficient follow-up time (two years before and one year after DP). Most patients (61%) used neuropathic pain medications during the follow-up, while 44% used antidepressants. Most patients (70%, n = 19) retired because of dorsopathies. The dose of gabapentinoids started to increase before the DP; after the DP, the doses started to increase again after the decrease but remained at a lower level. Conclusions. Neuropathic pain medication and antidepressant use suggest that pain continues after the DP—that is, pensioners continue to experience inconvenient chronic pain. Resources for patient care are therefore needed after the DP. However, the DP reduces the dose increase of gabapentinoids; the dose is higher immediately before retirement than at the end of the follow-up.