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Zhaochen Zhu,1,2,* Renzhi Gao,1,2,* Teng Ye,1,2 Kai Feng,1,2 Juntao Zhang,2 Yu Chen,2 Zongping Xie,1 Yang Wang2 1Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, People’s Republic of China; 2Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 200233, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zongping Xie, Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600# Yishan Road, Shanghai, 200233, People’s Republic of China Email x91034@qq.comBackground: Tendinopathy is a common cause of tendon pain. However, there is a lack of effective therapies for managing tendinopathy pain, despite the pain being the most common complaint of patients. This study aimed to evaluate the therapeutic effect of small extracellular vesicles released from induced pluripotent stem cell-derived mesenchymal stem cells (iMSC-sEVs) on tendinopathy pain and explore the underlying mechanisms.Methods: Rat tendinopathy model was established and underwent the injection of iMSC-sEVs to the quadriceps tendon one week after modeling. Pain-related behaviors were measured for the following four weeks. Tendon histology was assessed four weeks after the injection. To further investigate the potential mechanism, tenocytes were stimulated with IL-1β to mimic tendinopathy in vitro. The effect of iMSC-sEVs on tenocyte proliferation and the expression of proinflammatory cytokines were measured by CCK-8, RT-qPCR, and ELISA. RNA-seq was further performed to systematically analyze the related global changes and underlying mechanisms.Results: Local injection of iMSC-sEVs was effective in alleviating pain in the tendinopathy rats compared with the vehicle group. Tendon histology showed ameliorated tendinopathy characteristics. Upon iMSC-sEVs treatment, significantly increased tenocyte proliferation and less expression of proinflammatory cytokines were observed. Transcriptome analysis revealed that iMSC-sEVs treatment upregulated the expression of genes involved in cell proliferation and downregulated the expression of genes involved in inflammation and collagen degeneration.Conclusion: Collectively, this study demonstrated iMSC-sEVs protect tenocytes from inflammatory stimulation and promote cell proliferation as well as collagen synthesis, thereby relieving pain derived from tendinopathy. As a cell-free regenerative treatment, iMSC-sEVs might be a promising therapeutic candidate for tendinopathy.Keywords: tendinopathy, pain relief, extracellular vesicles, iPSC derived MSC

The article deals with local injection therapy (LIT) in arthrological practice, the purpose of which is the introduction of a drug into the joint cavity or periarticularly, removal of excess synovial fluid from the joint cavity with subsequent analysis of its composition for differential diagnosis and decision-making on treatment tactics. The most commonly used in LIT are glucocorticoids, hyaluronic acid (GlK), autologous platelet-rich plasma. The method of introducing GLA into the joint cavity is considered by experts as a promising method for the treatment of osteoarthritis, the most common chronic joint disease. GlK-based preparations differ in concentration, molecular weight and production method. The article presents the results of studies using high- or low-molecular drugs GlK in the treatment of patients with osteoarthritis of the knee, hip and small joints. Attention is drawn to the fact that LIT with GlK preparations is used in the treatment of other diseases of the musculoskeletal system. Data are presented, including those of Russian authors, on the effectiveness of GlK in OA of the shoulder joints, in the syndrome of compression of the shoulder rotators. Thus, the restoration of range of motion and a significant reduction in pain in the shoulder area was achieved against the background of the use of 3 to 5 injections of the GlK preparation produced in the Russian Federation by bacterial fermentation. The unique production technology of the GlK preparation makes it possible to reduce the risk of bacterial endotoxins, completely purify the solution from hyaluronidase, increase homogeneity, and preserve the molecular weight. On the basis of the obtained evidence of efficacy and safety, HLA preparations are included by various medical associations and professional communities in Russian and international clinical guidelines for the treatment of OA.

Abstract Background Sterile water injections can provide effective pain relief during childbirth, particularly for low back pain related to childbirth. However, the pain associated administering the injections can negatively impact women’s impressions of the procedure. It may discourage women from considering repeat doses despite the quality of analgesia experienced. Determining strategies to reduce the pain related to the administration of sterile water injections would improve the acceptability of the technique. Therefore, the aim of this study was to evaluate the effect of topical local anesthesia on the pain associated with administration of sterile water injections. Methods The study was designed as a multi-arm single-blind, randomized, controlled trial and 120 female healthy students were randomly divided according to one of four groups. The Intervention group received sterile water injections with topical local anesthesia. Control group 1 received sterile water injections without topical local anesthesia, control group 2 received injections of isotonic saline 0.9% with topical local anesthesia and control group 3 received injections of isotonic saline 0.9% without topical local anesthesia. Pain Immediately after the injections and subsidence in pain were recorded using a visual analogue scale. Sensations in the injection area were reported 15 min and the day after the injections. Results The main finding of this study was that local anesthesia with EMLA® reduces the pain associated with the administration of intracutaneous sterile water injections. There was a significant difference in the self-assessed pain score immediately following the injections between the control (73.3 mm) and intervention groups (50.0 mm), p = 0.001. No adverse side effects were reported. Conclusion Local anesthesia with EMLA® reduces the pain associated with intracutaneous administration of sterile water injections. Trial registration The study was registered 08/07/2014 at ClinicalTrials.gov Identifier: NCT02213185 .

Introduction: Epidural analgesia is one of the preferred mode of perioperative management. Neuraxial opioids like fentanyl when used in epidural offer advantage of augmenting local anaesthetic effect and reducing the anaesthetic and analgesic requirement. Aim: To compare the adequacy of analgesia, requirement of rescue analgesics between 0.125% bupivacaine with 2 mcg/cc fentanyl and 0.125% levobupivacaine with 2 mcg/cc fentanyl. Materials And Methods: The randomised clinical study was carried out from September 2016 to May 2017 in 70 patients (35 in each group) of American Society of Anaesthesiologists (ASA) 1 and 2 scheduled for elective gynae-oncological surgeries. The epidural analgesia in group Bupivacaine with Fentanyl (BF) was 0.125% Bupivacaine with 2 mcg/cc Fentanyl and group Levobupivacaine with Fentanyl (LF) was 0.125% Levobupivacaine with 2 mcg/cc fentanyl. All data was statistically analysed and compared using Student t-test, Chi-square/Fisher-Exact test. Results: Total of 70 patients were analysed, 35 each in Group BF (mean age: 50.06±7.19 years) and Group LF (mean age: 46.43±8.41 years). Both the groups were compatible with regard to demographic data and haemodynamic variables. The mean Visual Analogue Scale (VAS) score was higher in group BF compared to group LF at 0,1,4,6,1,2 and 18 hours but the observed difference in both the groups was not statistically significant except at 2nd (p-value: 0.016) and 24th hour (p-value 0.017). Number of rescue analgesics as epidural boluses (p-value=0.001) and paracetamol (p-value=0.044) requirement were more in group BF compared to group LF respectively. Conclusion: On account of adequate postoperative analgesia, haemodynamic stability, levobupivacaine with fentanyl is a better option than bupivacaine with fentanyl for epidural infusion.

Relief of ongoing pain is a potent motivator of behavior, directing actions to escape from or reduce potentially harmful stimuli. Whereas endogenous modulation of pain events is well characterized, relatively little is known about the modulation of pain relief and its corresponding neurochemical basis. Here, we studied pain modulation during a probabilistic relief-seeking task (a ‘wheel of fortune’ gambling task), in which people actively or passively received reduction of a tonic thermal pain stimulus. We found that relief perception was enhanced by active decisions and unpredictability, and greater in high novelty-seeking trait individuals, consistent with a model in which relief is tuned by its informational content. We then probed the roles of dopaminergic and opioidergic signaling, both of which are implicated in relief processing, by embedding the task in a double-blinded cross-over design with administration of the dopamine precursor levodopa and the opioid receptor antagonist naltrexone. We found that levodopa enhanced each of these information-specific aspects of relief modulation but no significant effects of the opioidergic manipulation. These results show that dopaminergic signaling has a key role in modulating the perception of pain relief to optimize motivation and behavior.

Background: Recently, cryotherapy has become a common practice for postoperative pain management. The current accepted practice in Japan is the use of cryotherapy at 5 °C after arthroscopic shoulder surgery. However, this therapy has been reported to be highly intense because the sustained low temperature causes discomfort for patients. The optimum temperature and duration of cooling required for comfortable and effective cryotherapy after arthroscopic shoulder surgery were investigated. Methods: Because pain levels might differ depending on the condition, we selected 52 patients with rotator cuff injuries, which were the most common disorders indicated for arthroscopic shoulder surgery. Patients were treated with cryotherapy at 5 °C or 10 °C for 16 h or 24 h. The pain level was determined using the visual analogue scale, and deep shoulder joint temperatures were recorded at different time points for analysis. Results: Pain after arthroscopic shoulder surgery was found to be related to the presence of a brachial plexus block using the interscalene approach during surgical anesthesia. To obtain effective analgesia with cryotherapy, the cooling temperature and duration of cryotherapy had to be changed based on the presence or absence of the brachial plexus block. Patients who received brachial plexus blocks had the lowest recorded pain scores after receiving cryotherapy at 5 °C for 24 h after surgery. Patients who did not receive the block had the lowest recorded pain scores when receiving cryotherapy at either 5 °C for 16 h or 10 °C for 24 h. Conclusions: Using universal cryotherapy intensity and duration settings regardless of the use of other interventions is likely to unintentionally increase postoperative pain levels. This study revealed that cryotherapy at 5 °C for 24 h was optimal for patients who received an anesthesia block and at 5 °C for 16 h or at 10 °C for 24 h for those who did not receive the anesthesia block. These results can be used as a reference for setting the temperature and duration of cryotherapy after arthroscopic shoulder surgery. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is a complex chronic disease that affects approximately 10% of women of reproductive age worldwide and commonly presents with pelvic pain and infertility. Method & outcome measures: A systematic review of the literature was carried out using the databases Pubmed, Scopus, Cochrane and ClinicalTrials.gov in women with a confirmed laparoscopic diagnosis of endometriosis receiving progestins to determine a reduction in pain symptoms and the occurrence of adverse effects. Results: Eighteen studies were included in the meta-analysis. Progestins improved painful symptoms compared to placebo (SMD = −0.61, 95% CI (−0.77, −0.45), P < 0.00001) with no comparable differences between the type of progestin. After median study durations of 6–12 months, the median discontinuation rate due to adverse effects was 0.3% (range: 0 − 37.1%) with mild adverse effects reported. Conclusion: The meta-analysis revealed that pain improvement significantly increased with the use of progestins with low adverse effects. Systematic Review Registration: PROSPERO CRD42021285026. [ABSTRACT FROM AUTHOR]

Background: The optimal dosage for opioids given to patients after surgery for pain management remains controversial. We examined the association of higher post-surgical opioid use with pain relief and recovery. Methods: We retrospectively enrolled adult patients who underwent elective abdominal surgery at our hospital between August 2021 and April 2022. Patients were divided into the "high-intensity" or "low-intensity" groups based on their post-surgical opioid use. Generalized estimating equation models were used to assess the associations between pain scores at rest and during movement on days 1, 2, 3, and 5 after surgery as primary outcomes. The self-reported recovery and incidence of adverse events were analyzed as secondary outcomes. Results: Among the 1170 patients in the final analysis, 293 were in the high-intensity group. Patients in the high-intensity group received nearly double the amount of oral morphine equivalents per day compared to those in the low-intensity group (84.52 vs. 43.80), with a mean difference of 40.72 (95% confidence interval (CI0 38.96–42.48, p < 0.001) oral morphine equivalents per day. At all timepoints, the high-intensity group reported significantly higher pain scores at rest (difference in means 0.45; 95% CI, 0.32 to 0.58; p < 0.001) and during movement (difference in means 0.56; 95% CI, 0.41 to 0.71; p < 0.001) as well as significantly lower recovery scores (mean difference (MD) −8.65; 95% CI, −10.55 to −6.67; p < 0.001). A post hoc analysis found that patients with moderate to severe pain during movement were more likely to receive postoperative high-intensity opioid use. Furthermore, patients in the non-high-intensity group got out of bed sooner (MD 4.31 h; p = 0.001), required urine catheters for shorter periods of time (MD 12.26 h; p < 0.001), and were hospitalized for shorter periods (MD 1.17 days; p < 0.001). The high-intensity group was at a higher risk of chronic postsurgical pain (odds ratio 1.54; 95% CI, 1.14 to 2.08, p = 0.005). Conclusions: High-intensity opioid use after elective abdominal surgery may not be sufficient for improving pain management or the quality of recovery compared to non-high-intensity use. Our results strengthen the argument for a multimodal approach that does not rely so heavily on opioids. [ABSTRACT FROM AUTHOR]

Pain involves both sensory and affective dimensions. The amygdala is a key player in linking nociceptive stimuli to negative emotional behaviors or affective states. Relief of pain is rewarding and activates brain reward circuits. Whether the reward circuit from the ventral tegmental area (VTA) to the central amygdala (CeA) is involved in pain relief remains unexplored. Using a model of experimental postsurgical pain, we found that pain relief elicited conditioned place preference (CPP), activated CeA-projecting dopaminergic cells in the VTA, and decreased dopaminergic D2 receptor expression in the CeA. Activation of the VTA–CeA neural pathway using optogenetic approaches relieved incisional pain. Administration of a D2 receptor agonist reversed the pain relief elicited by light-induced activation of the VTA-CeA pathway. These findings indicate that the VTA-CeA circuit is involved in pain relief in mice via dopamine receptor D2 in the CeA. [ABSTRACT FROM AUTHOR]

Feline oral squamous cell carcinoma (FOSCC) is the most common oral tumour diagnosed in pet cats and carries a poor prognosis with <10% one‐year survival despite multi‐modal therapies. Tumours of the mandible or maxilla are frequently osteo‐invasive and pain can result from osteolysis. Zoledronate is a bisphosphonate that inhibits osteoclasts and reduces bone resorption. Radiation therapy (RT) is used to treat FOSCC due to anti‐cancer activity and ability to improve quality of life. We hypothesized RT can be safely combined with zoledronate, and that this combinatory therapy would be efficacious, well tolerated, and result in decreased bone resorption in cats with FOSCC. SCCF1 cell line was treated with zoledronate before, concurrently, or after RT, and clonogenic assays were performed to determine if an optimal dosing schedule would be identified. Nine cats with osteoinvasive FOSCC were recruited for treatment with 4 weekly doses of 8 Gy RT combined with zoledronate administered at the first and fourth treatments. Serial CT scans were performed to assess tumour response. Safety and tolerability were monitored with hematologic and biochemical parameters, and acute radiation effects were characterized. Serum c‐telopeptide (CTx) and relative bone mineral density (rBMD) by dual ‐energy X‐ray absorptiometry (DEXA) quantified bone resorption. In vitro studies showed no clear benefit to timing of zoledronate with RT, therefore all zoledronate was administered concurrently with RT in FOSCC patients. Based on tumour volume, 4/9 (44.4%) cats achieved partial remission, 4/9 (44.4%) stable disease and 1/9 (11.1%) had progressive disease. The combinatory therapy was well‐tolerated based on biochemical measurements, and all patients experienced decreased serum CTx. Combining RT with zoledronate in tumour‐bearing cats is safe, well‐tolerated, results in a partial remission rate of up to 44%, and decreases serum CTx, a marker of bone resorption. [ABSTRACT FROM AUTHOR]

Background: Perimenstrual migraine attacks in women with menstrual migraine is difficult to treat. This post-hoc analysis evaluated the efficacy of lasmiditan, a high affinity and selective 5-HT1F receptor agonist, for perimenstrual attacks.Methods: Patients from two randomized, double-blind, placebo-controlled clinical trials (MONONOFU and CENTURION) were instructed to treat an attack with a single dose of study medication within four hours of pain onset. After dosing, the proportion of patients who achieved freedom from migraine-related head pain, most bothersome symptom, and disability was reported at baseline up to 48 hours after dose and pooled data were evaluated.Results: A total of 303 patients (MONONOFU N = 78; CENTURION N = 225) treated perimenstrual migraine attacks with lasmiditan 50 mg (N = 24), 100 mg (N = 90), 200 mg (N = 110), and placebo (N = 79). More patients achieved migraine-related head pain freedom with lasmiditan 200 mg versus placebo at all time points assessed. At 2 hours, 33.6% of patients in the 200-mg group (p < 0.001), and 16.7% of patients in the 100-mg (p = 0.11) and 50-mg (p = 0.19) groups were pain free, compared with 7.6% in the placebo group.Conclusions: Lasmiditan treatment of perimenstrual migraine attacks was associated with freedom from migraine-related head pain at two hours, early onset of efficacy, and sustained efficacy.Clinical Trial registration: NCT03962738 and NCT03670810. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the evidence from randomized clinical trials (RCTs) about the effect of music intervention in reducing patients' anxiety during breast biopsy.Methods: Electronic databases including PubMed, Cochrane Library, Scopus, and Web of Science were searched using the relevant MeSH terms. The inclusion criteria were all RCTs assessing the effect of music therapy versus no music in reducing anxiety during breast biopsy. The extracted outcomes were anxiety and pain during breast biopsy. They were pooled as mean difference (MD) with a 95% confidence interval (CI) in a fixed-effects model, using Review Manager 5.3 software for windows. The quality of included studies was assessed with the Cochrane risk of bias assessment tool (RoB 1.0). Then, the outcomes of our meta-analyses were independently evaluated by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to know the grade of their evidence.Results: The final analysis included five RCTs. We found a positive effect of music therapy in reducing anxiety levels compared with control group (MD =  - 2.11; 95% CI (- 4.16 to - 0.06); p = 0.04). No difference between music and control groups regarding pain associated with breast biopsy (MD = 0.22; 95% CI (- 0.81 to 1.25); p = 0.68). The GRADE rating of our outcomes was low for anxiety levels and very low for pain during the biopsy.Conclusions: Music therapy could be an effective, simple, non-pharmacological option in relieving anxiety during breast biopsy; however, it had no effect on procedure-associated pain. More large and high-quality studies are needed to confirm our results. [ABSTRACT FROM AUTHOR]

This systematic review aims to evaluate the effectiveness of pharmacological and non-pharmacological strategies for pain relief in women during contrast-enhanced ultrasound for the assessment of tubal patency and uterine disease, compared with placebo or no intervention. In December 2021, we searched the electronic databases (Pubmed, Embase, Sciencedirect, the Cochrane library and Clinicaltrials.gov) without date restriction: We identified 10 randomized control trials (RCTs) (2098 women) eligible for this systematic review, after applying our inclusion and exclusion criteria. Among these, five studies compared the use of painkillers with the placebo, two studies compared different catheter positions in the cervix or in the uterine cavity, and two others considered different temperatures of the contrast medium, as a method to reduce pain. Topical lidocaine applied before the procedure may be associated with effective pain relief during hysterosonography, though the quality of this evidence is low. New echogenic contrast agents and their temperature at 37 °C ensure a less painful procedure. There is insufficient evidence to draw conclusions on the efficacy of other analgesics or strategies. [ABSTRACT FROM AUTHOR]

What is known and objective: Postoperative pain relief is a critical issue for hip arthroscopy surgery (HAS). This study aimed to investigate the effect of preemptive non‐steroidal anti‐inflammatory drugs (NSAIDs) for postoperative analgesia in femoroacetabular impingement (FAI) patients receiving HAS. Methods: This multicenter, randomized, controlled study enrolled 204 FAI patients receiving HAS, then assigned them to preoperative (PRE, N = 103) or postoperative (POS, N = 101) group as a 1:1 ratio; the PRE group administrated NSAIDs from 24 h pre‐surgery to day 7 (D7) post‐surgery, while the POS group administrated NSAIDs from 12 h post‐surgery to D7 post‐surgery. Results and discussion: Pain at rest was reduced at D1 (p = 0.016) and D2 (p = 0.023); pain at movement was decreased at D1 (p = 0.002), D2 (p = 0.020), and D3 (p = 0.030) in the PRE group compared with POS group, but not at other time points (all p > 0.05). Patient's satisfaction was increased at D1 (p = 0.013) and D3 (p = 0.029) in the PRE group compared to the POS group, but not at D7 (p = 0.145). Pethidine was less consumed at D3 (p = 0.038) and D7 (p = 0.017) in the PRE group in contrast with the POS group. Harris hip scores were similar at D7 (p = 0.124), month 1 (M1) (p = 0.273), and M3 (p = 0.360) between groups. Adverse events incidence was similar between groups (all p > 0.05). Besides, subgroup analysis discovered that pain was not influenced by the types of NSAID in both groups (all p > 0.05). What is new and conclusion: Starting NSAIDs before HAS provides better short‐term pain relief and improves patient's satisfaction compared with its postoperative utilization, while does not induce additional adverse events in FAI patients. [ABSTRACT FROM AUTHOR]

Glossopharyngeal nerve (GPN) block is a useful treatment option for acute post-tonsillectomy pain. This study aimed to assess safety and efficacy of the landmark (LM) technique versus the ultrasound (US)-guided technique for GPN block in children undergoing tonsillectomy. This double-blinded, parallel-group, randomized trial enrolled 54 children of both genders who were American Society of Anesthesiologists physical status grade I–II and were scheduled for tonsillectomy under general anesthesia. All patients underwent percutaneous peristyloid GPN block. In the LM group, 27 patients were managed by insertion of the needle at midpoint of the line between the mastoid process and angle of the mandible. In the US group, 27 patients were managed with the US-guided technique to locate the styloid process. The outcomes were time to first analgesic requirement, pain in rest and during swallowing, easiness of the technique, time required for the technique performance, recovery time from anesthesia, and anesthetist, surgeon, parent, and staff satisfaction. The post-tonsillectomy pain score during rest and swallowing, rescue analgesic request, recovery time from general anesthesia, anesthetist', surgeon', staff nurses', and parents' satisfactions were comparable between the LM technique and US-guided percutaneous peristyloid GPN block (all p ˃ 0.05). However, the LM technique was significantly easier and required shorter duration than the US-guided technique (p ˂ 0.05). In tonsillectomy surgery, both the LM technique and the percutaneous peristyloid US-guided GPN block were safe and effective in reducing postoperative pain. Furthermore, the LM technique was easier and had shorter duration to perform than the US-guided technique. [ABSTRACT FROM AUTHOR]

A grade 3 burn is a nonstatic fatal injury, which can lead to complete damage to the skin structure, accompanied by a series of symptoms such as persistent inflammation, pain, pruritus, ulcer, and peripheral neuropathy. Although the primary clinical burn treatment is skin grafting, it cannot comprehensively solve burn symptoms. Here, a multifunctional DNA hydrogel integrated system is conveniently obtained through dynamic cross‐linking of the DNA unit, polyacrylamide, and l‐ascorbate 2‐phosphate (l‐A2P) formation of dense hydrogen bonds. The DNA hydrogel is doped with borneol for pain and itch relief. The obtained DNA hydrogel provides a hotbed similar to the extracellular matrix structure in vivo for the growth and development of stem cells, which can regulate cell proliferation, maintain cell viability, and achieve perfect release in a suitable environment. Additionally, the pharmacological wound dressing shell features excellent mechanical behavior, tissue adhesion, and antibacterial properties. Beyond that, the multifunctional DNA hydrogel integrated system can promote macrophage transformation, angiogenesis, and neurogenesis. Notably, the system activates the phosphatidylinositol 3′‐kinase (PI3K)‐Akt signaling pathway, which helps to promote tissue regeneration. Therefore, the DNA hydrogel integrated system opens the cascade mode of effective integrated treatment of burn wounds, further driving the in‐depth study of clinical transformation mechanisms in the future. [ABSTRACT FROM AUTHOR]

Background: Stress fractures occur to the musculoskeletal system on a frequent basis. This injury in the foot and ankle is relatively benign and treated conservatively with a walking boot or postoperative shoe. The use of an injectable bone graft has shown success with bone marrow edema and osteoarthritis in the knee, thus the same effects would be seen worthy of stress fractures relating to other parts of the body such as the foot and ankle. The foot and ankle sustains a high level of stress and is prone to stress fractures. This retrospective analysis documents several cases of stress fractures treated with an injectable allograft. Methodology/Procedures: A retrospective analysis was conducted on twenty-eight individuals, ages 20-75, who underwent bone repair with an injectable calcium phosphate graft by one of the study investigators. Diagnosis was made with MRI imaging studies prior to surgical intervention. Intraoperatively, fluoroscopy was used to identify the surgical site to be injected. After appropriate targeted position of a cannula, the graft was injected into the site of injury. Retrospective analysis was performed by chart review and phone contact to each participant with a minimum follow-up of twelve months post-procedure. A prewritten questionnaire was used to acquire patient and procedure feedback after verbal consent was obtained. Results: A total of twenty-seven patients were evaluated. Thirteen underwent injection of bone graft for calcaneal stress fractures, six for talus stress fractures, three for metatarsal fractures, and one for a fibula fracture. One individual presented with both a calcaneus and a talus stress fracture, one with a cuboid and a metatarsal fracture and two patients with both metatarsal and cuneiform fractures. Of those represented in this trial, 24 out of the 27 patients felt no pain and were back to their normal lifestyle and routines four weeks post-procedure. At their 12-month follow-up questionnaire conducted verbally, patients continued to report no pain and actively had resumed their lifestyles. Discussion: The analysis showed that 80% of participants had a minimum of 75% relief twelve-months post-procedure. Only 3/25 patients reported a level 5 or higher on a pain scale of 10, after the use of this treatment. Most participants returned to lifestyle activities quickly and were pain-free after a short postoperative period of treating their bone marrow lesion. [ABSTRACT FROM AUTHOR]

Trigeminal neuralgia is a chronic pain condition associated with sharp, shock-like pain in one or more divisions of the trigeminal nerve. For patients who do not respond well to pharmacotherapy, there is growing evidence that Botulinum toxin type A injections into the trigeminal ganglion provide pain relief for several weeks up to several months at a time. One option is to administer injections into the trigeminal ganglion in Meckel's cave by inserting a needle through the Pterygopalatine Fossa using fluoroscopy to guide and confirm the proper needle placement. However, there is evidence that Botulinum toxin travels across nerve synapses; thus, injecting directly into the trigeminal ganglion may not be necessary. We present two patients with a confirmed diagnosis of trigeminal neuralgia who were treated by injecting Botulinum toxin type A intraorally into the mental foramen which resulted in 6 months or longer of pain relief. Injections into the mental foramen are much easier to administer than those administered directly into the trigeminal ganglion, and both patients treated with this technique experienced comparable results to what can be expected from traditional fluoroscopy-guided botulinum toxin injections. Though more research is needed, these cases potentially imply that a less-invasive injection may be sufficient in managing trigeminal neuralgia-related pain. [ABSTRACT FROM AUTHOR]

Background: Sterile water injections can provide effective pain relief during childbirth, particularly for low back pain related to childbirth. However, the pain associated administering the injections can negatively impact women's impressions of the procedure. It may discourage women from considering repeat doses despite the quality of analgesia experienced. Determining strategies to reduce the pain related to the administration of sterile water injections would improve the acceptability of the technique. Therefore, the aim of this study was to evaluate the effect of topical local anesthesia on the pain associated with administration of sterile water injections. Methods: The study was designed as a multi-arm single-blind, randomized, controlled trial and 120 female healthy students were randomly divided according to one of four groups. The Intervention group received sterile water injections with topical local anesthesia. Control group 1 received sterile water injections without topical local anesthesia, control group 2 received injections of isotonic saline 0.9% with topical local anesthesia and control group 3 received injections of isotonic saline 0.9% without topical local anesthesia. Pain Immediately after the injections and subsidence in pain were recorded using a visual analogue scale. Sensations in the injection area were reported 15 min and the day after the injections. Results: The main finding of this study was that local anesthesia with EMLA® reduces the pain associated with the administration of intracutaneous sterile water injections. There was a significant difference in the self-assessed pain score immediately following the injections between the control (73.3 mm) and intervention groups (50.0 mm), p = 0.001. No adverse side effects were reported. Conclusion: Local anesthesia with EMLA® reduces the pain associated with intracutaneous administration of sterile water injections. Trial registration: The study was registered 08/07/2014 at ClinicalTrials.gov Identifier: NCT02213185. [ABSTRACT FROM AUTHOR]

Background: Pain relief is one of the main objectives of radiotherapy for cancer patients with bone metastases. Stereotactic body radiotherapy (SBRT) enables precise delivery of a higher dosage to the target area. Several trials have reported comparisons between SBRT and conventional radiotherapy (cRT) in patients with painful bone metastasis. However, the results of those investigations were inconsistent, and no systematic review or meta-analysis has been done till now. Methods: We systematically searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and Clinicaltrials.gov up to May 1, 2022 for relevant studies. Patients with painful bone metastasis who received SBRT or cRT were included. The primary outcome was the patients' pain response rate at three months. The secondary outcomes included the rate of pain responders at one month and six months, oral morphine equivalent dose (OMED) use, and any adverse events. STATA software 12.0 was used for the statistical analysis. Results: We collected 533 patients' data from 4 randomized controlled trials (RCTs), there was a significant difference of pain response rate at 3 months between two groups (RR = 1.41, 95% CI: 1.12-1.77, I² = 0.0%, P = 0.003). However, no significant difference was found in pain response rate at 1 month (RR = 1.19, 95% CI: 0.91-1.54, I² = 31.5%, P = 0.201) and 6 months (RR = 1.25, 95% CI: 0.93-1.69, I² = 0.0%, P = 0.140). OMED consumption was not significantly different in patients treated with SBRT compared with control group (WMD = -1.11, 95% CI: -17.51-15.28, I² = 0.0%, P = 0.894). For safety outcome, no statistical difference was found between SBRT and cRT (RR = 0.72, 95% CI: 0.46-1.14, I² = 20.1%, P = 0.162). Conclusion: This study shows that for painful bone metastases, patients with SBRT experienced better pain relief 3 months after radiation than patients with cRT, and SBRT did not increase the incidence of adverse events. [ABSTRACT FROM AUTHOR]

Neurostimulation-based therapeutic approaches are emerging as alternatives to pharmacological drugs, but need further development to optimize efficacy and reduce variability. Despite its key relevance to pain, the insular cortex has not been explored in cortical neurostimulation approaches. Here, we developed an approach to perform repetitive transcranial direct current stimulation of the posterior insula (PI tDCS) and studied its impact on sensory and aversive components of neuropathic pain and pain-related anxiety and the underlying neural circuitry in mice using behavioral methods, pharmacological interventions and the expression of the activity-induced gene product, Fos. We observed that repetitive PI tDCS strongly attenuates the development of neuropathic mechanical allodynia and also reverses chronically established mechanical and cold allodynia for several weeks post-treatment by employing descending opioidergic antinociceptive pathways. Pain-related anxiety, but not pain-related aversion, were inhibited by PI tDCS. These effects were associated with a long-term suppression in the activity of key areas involved in pain modulation, such as the cingulate, prefrontal and motor cortices. These data uncover the significant potential of targeting the insular cortex with the objective of pain relief and open the way for more detailed mechanistic analyses that will contribute to improving cortical neurostimulation therapies for use in the clinical management of pain. [ABSTRACT FROM AUTHOR]

In recent years, activation of thermal transient receptor potential (TRP) ion channels at a range of temperatures has received widespread attention as a target for traditional Chinese medicine (TCM) to regulate body temperature and relieve pain. Discovery of transient receptor potential vanilloid 1 (TRPV1) was awarded a Nobel Prize, reflecting the importance of these channels. Here, the regulatory effects of TCMs and their active ingredients on TRP ion channels are reviewed, and future directions for research on the cold, hot, warm, cool, and neutral natures of TCMs are considered. In herbs with cold, hot, warm, cool, and neutral natures, we found 29 TCMs with regulatory effects on TRP ion channels, including Cinnamomi Cortex, Capsici Fructus, Rhei Radix et Rhizoma, Macleayae cordatae Herba, Menthae Haplocalycis Herba, and Rhodiolae Crenulatae Radix et Rhizoma. Although some progress has been made in understanding the regulation of TRP ion channels by TCMs and their ingredients, the molecular mechanism by which TCMs have this effect remains to be further studied. We hope this review will provide a reference for further research on the cold, hot, warm, cool, and neutral natures of TCMs. [ABSTRACT FROM AUTHOR]

Objective: To analyse the efficacy of sacrospinous ligament (SSL) suture removal on the reduction of pain symptoms in the case of suspected pudendal nerve entrapment after sacrospinous ligament fixation (SSLF). Design: Retrospective cohort study. Setting: Tertiary referral centre, the Netherlands. Population A cohort of 21 women having their SSLF sutures removed because of SSLF‐related pain symptoms. Methods: Clinical record review. Main outcome measures: The primary outcome was reduction of pain after SSL suture removal. Secondary outcome measures were time interval between suture placement and suture removal, complete suture removal, adverse events and recurrence of pelvic organ prolapse (POP). Results: A total of 21 women underwent SSL suture removal for severe and/or persistent pain, which was confirmed on clinical examination: 95% of the women (20/21) reported pain reduction after suture removal, and 57% reported complete pain relief. The time interval between suture placement and suture removal was at a median of 414 days (range 8–1855 days). Sutures could be completely removed in 86% of cases (18/21). One woman had excessive blood loss (520 ml) without blood transfusion. At 6–8 weeks after surgery, 10% of the women (2/21) had renewed symptomatic POP, stage ≥ 2, for which additional POP surgery was indicated. Conclusions: When performed by an experienced clinician, SSL suture removal is feasible and efficacious, with low morbidity. In addition, the risk of recurrent POP in the short term appeared to be low. The surgical removal of sacrospinous ligament sutures is safe and efficacious for pain relief, even remote from initial placement. The surgical removal of sacrospinous ligament sutures is safe and efficacious for pain relief, even remote from initial placement. [ABSTRACT FROM AUTHOR]

In low-income settings, postoperative pain relief could be challenging as a high patient/nurse ratio limits pain assessment and adequate analgesics administration. The multi-center prospective double-blinded parallel randomized controlled trial was done to compare lidocaine, tramadol, and placebo (saline) intraoperative wound infiltration to relieve post-cesarean section wound pain during the first 24 h. Ninety-nine cases were equally randomized into three groups, each containing 33 pregnant women undergoing cesarean section under general anesthesia. During operation, the wound was infiltrated subcutaneously with 20 mL of 2% lidocaine solution in the first group, 2 mg/kg tramadol in the second group, and saline in the third group. The primary outcome was to assess the postoperative pain at 2, 4, 6, 12, and 24 h by the Yes-No-Don't Know (YNDK) Scale, while the secondary outcome was to assess the need for further postoperative analgesia. Wound infiltration with lidocaine or tramadol was effective in pain relief, and both were superior to placebo. Wound infiltration with tramadol was superior to lidocaine in pain relief at 2 h and up to 24 h. Wound infiltration with tramadol has a more prolonged pain relief effect than lidocaine in post-cesarean section pain relief in patients performing cesarean section under general anesthesia lasting up to 24 h, and both are superior to placebo in pain relief. [ABSTRACT FROM AUTHOR]

Aim: Our aim was to compare the outcomes of waterbirths and conventional births in a Finnish hospital setting for the first time. Methods: This retrospective study compared waterbirths with conventional low‐risk deliveries from September 2018 to March 2021 at a level‐two hospital in Finland. Cases and controls were collected from the patient records database. Results: The study comprised 78 waterbirths and 1623 matched conventional births. Mothers in the waterbirth group only required a quarter of the amount of pain medication required by those in the control group. Babies born in water had slightly lower birth temperatures than those born conventionally (36.6 versus 36.8°C). Umbilical cord artery and vein pH were slightly higher in the waterbirth group than in the control group (artery 7.31 versus 7.28 and vein 7.38 versus 7.35). The Apgar scores did not differ. Hospital stays were shorter in the waterbirth group than in the conventional birth group (1.90 versus 2.33 days). Babies in the waterbirth group were significantly less likely to require formula than those in the conventional birth group during their hospital stay. Conclusion: Waterbirth decreased the requirement for maternal pain medication and favoured greater breastfeeding and earlier discharge. Prospective studies must confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Adequate pain relief, early restoration of breathing, and rapid mobilization pose a clinical challenge in patients with blunt chest trauma. Virtual reality (VR) has the potential to achieve these 3 interrelated treatment objectives with enhanced self-efficacy and autonomy of patients and limited support by clinicians., Objective: This study aimed to assess the effectivity of breathing and physical exercises using VR on the pulmonary recovery of patients with blunt chest trauma at the ward., Methods: A pilot randomized controlled trial was performed. The control group received usual physiotherapy consisting of protocolized breathing exercises (8 times daily for 10 minutes) and physical exercises (2 times daily for 10 minutes). The VR group was instructed to perform these exercises using VR. The primary outcome was vital lung capacity at day 5 or earlier at discharge. Secondary outcomes were patient mobility (time standing, lying, and sitting), clinical outcomes (length of hospital stay, pulmonary complications, transfer to intensive care unit, and readmission within 30 days), pain, activities of daily living, patient-reported outcome measures (satisfaction and quality of recovery). Patient experiences and barriers and facilitators toward implementation were assessed through interviews., Results: The study was prematurely ended due to enrollment failure combined with poor protocol adherence to exercises in both groups. A total of 27 patients were included, of which 19 patients completed 3 or more days. Vital lung capacity at 5 days (or last measurement) was equal between groups with 1830 (SD 591) mL and 1857 (SD 435) mL in the control and VR groups, respectively. No marked differences were observed in secondary outcomes. Patient interviews showed positive attitudes toward the use of VR, describing that visualization of the exercises helped patients to perform the exercises correctly and to continue the exercises for a longer duration. Also, patients experienced the immersiveness of VR as an analgesic. However, patients did not experience added value over usual care and reported that better integration in treatment and the hectic hospital environment could improve the use of the VR exercises., Conclusions: The suitability of patients to use virtual reality therapy (VRx) in a hospital (trauma) ward setting is lower than generally expected. Effective application of VRx requires professional guidance and needs thorough alignment with clinical practice. For future research, we recommend to chart adherence to study protocol before designing a VR clinical trial. Patient-reported experiences need to be prioritized in evaluating VR acceptance, usability, and effectiveness. In line, we recommend performing a systematic analysis (eg, using the technology acceptance model) on the acceptance before pilot or main effectiveness studies. Finally, the eligibility of patients and exclusion of patients due to the inability to use VRx should be routinely reported., Trial Registration: ClinicalTrials.gov NCT05194176; https://tinyurl.com/2bzh4tzx., (©Tjitske D Groenveld, Indy GM Smits, Naomi Scholten, Marjan de Vries, Harry van Goor, Vincent MA Stirler. Originally published in JMIR Serious Games (https://games.jmir.org), 09.12.2024.)

Most patients with primary osteoarthritis of the elbow report a history of heavy lifting work with the affected upper limb. Conservative treatment, including activity modifications, nonsteroidal anti-inflammatory drug (NSAID) intake, and intra-articular injections can provide sufficient pain relief in the early stages when used in combination. If surgery is required, many patients experience significant pain relief from joint-preserving procedures despite existing cartilage damage. Although open debridement procedures are effective, arthroscopic osteocapsular arthroplasty has become established as the preferred surgical procedure. The ulnar nerve should be assessed during surgery and treated if necessary. Total elbow arthroplasty (TEP) is successful in terms of pain relief and function; however, it is recommended for older patients with advanced osteoarthritis or for whom joint-preserving procedures have failed., Competing Interests: Einhaltung ethischer Richtlinien. Interessenkonflikt: Gemäß den Richtlinien des Springer Medizin Verlags werden Autorinnen und Autoren sowie die Wissenschaftliche Leitung im Rahmen der Manuskripterstellung und Manuskriptfreigabe aufgefordert, eine vollständige Erklärung zu ihren finanziellen und nichtfinanziellen Interessen abzugeben. Autoren: A. Lenich: A. Finanzielle Interessen: A. Lenich gibt an, dass kein finanzieller Interessenkonflikt besteht. – B. Nichtfinanzielle Interessen: Niedergelassener Unfallchirurg ZEST in Move MVZ Orthopädie am Stiglmaierplatz München | APL der Universität Regensburg, angestellt am Klinikum JOSEPHINUM München | Mitgliedschaften: DVSE aga DGU. N. Zumbansen: A. Finanzielle Interessen: N. Zumbansen gibt an, dass kein finanzieller Interessenkonflikt besteht. – B. Nichtfinanzielle Interessen: Aktuell: Angestellter Facharzt für Orthopädie und Unfallchirurgie, MOVE MVZ am Stiglmaierplatz, München; Davor: Assistenzarzt für Orthopädie und Unfallchirurgie, ISAR Klinikum/HELIOS Klinikum München West/Deutsches Schulterzentrum; München | Mitgliedschaften Gesellschaft/Berufsverband: AGA, DVSE, DKG, GOTS. Wissenschaftliche Leitung: Die vollständige Erklärung zum Interessenkonflikt der Wissenschaftlichen Leitung finden Sie am Kurs der zertifizierten Fortbildung auf www.springermedizin.de/cme . Der Verlag: erklärt, dass für die Publikation dieser CME-Fortbildung keine Sponsorengelder an den Verlag fließen. Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien. Für Bildmaterial oder anderweitige Angaben innerhalb des Manuskripts, über die Patient/-innen zu identifizieren sind, liegt von ihnen und/oder ihren gesetzlichen Vertretern/Vertreterinnen eine schriftliche Einwilligung vor., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Introduction: Hip osteoarthritis (OA) is a prevalent and debilitating condition, necessitating effective and safe treatment options. This systematic review aims to explore the potential of intra-articular mesenchymal stem cell (MSC) infiltrations as a therapeutic approach for hip OA., Methods: Following PRISMA guidelines, a systematic review was conducted, encompassing PubMed, Embase, and Cochrane Library databases. Inclusion criteria involved studies focusing on intra-articular MSC injections in patients with hip OA and reporting pain relief as an outcome measure. Quality assessment utilized the Newcastle-Ottawa scale and methodological index for non-randomized studies., Results: Ten studies were included in the review, exhibiting varied designs and sample sizes (316 patients). Outcome measures consisted of cartilage repair assessed through MRI and radiographies, pain scores (WOMAC, VAS, NRS), and functional improvements (HOS-ADL, OHS, FRI, PDQQ, LEFS). The studies reported favorable improvements in functional scores, pain relief, and cartilage repair/radiographic findings, with minimal reported adverse events., Conclusions: Intra-articular MSC infiltrations demonstrate promise as an effective and safe therapeutic intervention for managing hip OA, offering pain relief and functional enhancements. Nevertheless, limited high-quality studies and outcome measure variations underscore the need for further research to establish definitive treatment guidelines. Future investigations should address optimal MSC utilization, long-term outcomes, and potential complications to ensure the success of MSC-based therapies for hip OA management, ultimately improving patient outcomes. The findings provide valuable insights into the potential of MSC-based treatments for hip OA, advocating further rigorous research in this field., Trial Registration: The protocol was registered on PROSPERO database (CRD42023436973)., (© 2024. The Author(s).)

Overdose deaths from prescription opioids remain elevated, and policymakers seek solutions to curb opioid misuse. Recent proposals call for price-based solutions, such as opioid taxes and removal of opioids from insurance formularies. However, there is limited evidence on how opioid consumption responds to price stimuli. This study addresses that gap by estimating the effects of prices on the utilization of opioids, as well as other prescription painkillers. I use nationally representative individual-level data on prescription drug purchases and exploit the introduction of Medicare Part D in 2006 as an exogenous change in out-of-pocket drug prices. I find that new users have a relatively high price elasticity of demand for prescription opioids, and that consumers treat over-the-counter painkillers as substitutes for prescription painkillers. My results suggest that increasing out-of-pocket prices of opioids, through formulary design or taxes, may be effective in reducing new opioid use., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The introduction of the xxxxxxxx (GIBPS) technique represents a patient-centric novel and innovative method of ultrasound guided corticosteroid injection targeting the Glenohumeral joint (GHJ) and the Subacromial-Subdeltoid (SASD) bursa in a sequential manner, in the same setting. By integrating the two different sites of injection into a single technique, the procedure has the potential of transforming musculoskeletal interventional radiology and maximising patient care in shoulder pathologies. This procedure aims to reduce patient discomfort, optimise procedural efficiency, and enhance treatment precision through ultrasound guidance and improve the overall patient experience., (© 2024. Società Italiana di Ultrasonologia in Medicina e Biologia (SIUMB).)

A re-examination of clinical principles of long-term opioid therapy (LTOT) for chronic pain is long overdue amid the ongoing opioid crisis. Most patients on LTOT report ineffectiveness (poor pain control, function and health) but still find deprescribing challenging. Although prescribed as analgesics, opioids more likely provide pain relief primarily through reward system actions (enhanced relief and motivation) and placebo effect and less through antinociceptive effects. The unavoidable physiologic LTOT dependence can automatically lead to a paradoxical worsening of pain, disability and medical instability (maladaptive opioid dependence) without addiction due to allostatic opponent neuroadaptations involving reward/antireward and nociceptive/antinociceptive systems. This opioid-induced chronic pain syndrome (OICP) can persist/progress whether LTOT dose is maintained at the same level, increased, decreased or discontinued. Current conceptualization of LTOT as a straightforward long-term analgesic therapy appears incongruous in view of the complex mechanisms of opioid action, LTOT dependence and OICP. LTOT can be more appropriately conceptualized as therapeutic induction and maintenance of an adaptive LTOT dependence for functional improvement irrespective of analgesic benefits. Adaptive LTOT dependence should be ideally used for a limited time to achieve maximum functional recovery and deprescribed while maintaining functional gains. Patients on LTOT should be regularly re-evaluated to identify if maladaptive LTOT dependence with OICP has diminished any functional gains or leads to ineffectiveness. Ineffective LTOT (with maladaptive LTOT dependence) should be modified to make it safer and more effective. An adequately functional life without opioids is the ideal healthy long-term goal for both LTOT initiation and LTOT modification., (© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Objectives: This systematic review compares the long-term efficacy of cylindrical-lead spinal cord stimulation (CL-SCS) vs paddle-lead spinal cord stimulation (Paddle-SCS) for chronic pain management., Materials and Methods: We included prospective and retrospective studies with at least ten patients reporting on the efficacy of either lead type. Primary outcomes were pain score reduction (measured by the visual analog scale [VAS] and numeric rating scale [NRS]) and 50% pain relief after at least 12 months. Secondary outcomes included functional disability and complications, such as lead migration and infection rates. Meta-analyses compared effect sizes, while meta-regression and subgroup analyses addressed heterogeneity., Results: A total of 96 studies, comprising 7726 patients, met the inclusion criteria. Paddle-SCS demonstrated superior pain reduction, with a standardized mean difference (SMD) of 5.37 (95% CI [5.35, 5.38]) compared with CL-SCS, which had an SMD of 4.09 (95% CI [4.08, 4.10]) on the VAS. However, CL-SCS outperformed Paddle-SCS on the NRS, with SMDs of 4.39 vs 2.35, respectively. For 50% pain relief, Paddle-SCS had a success rate of 41.4%, as opposed to 35.4% for CL-SCS. Paddle-SCS showed a lower migration rate (4.3% vs 7.2% for CL-SCS) but higher infection rates (5.0% vs 3.3%)., Conclusions: Paddle-SCS offers superior pain reduction (as measured by the VAS) and a lower migration rate, but a higher infection risk compared with CL-SCS. CL-SCS showed better outcomes as measured by the NRS. The choice between Paddle-SCS and CL-SCS should be individualized according to patient-specific factors and treatment goals. Further research with rigorous study designs is needed to provide clearer comparisons between these interventions., Competing Interests: Conflict of Interest Damiano G. Barone is listed as an inventor on patent family members of international patent application PCT/GB2020/051684, published as WO 2021005382. The remaining authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The SMILE study addresses a significant need in palliative oncology by evaluating the non-inferiority of a shortened, 3-fraction stereotactic body radiotherapy (SBRT) schedule against the traditional 5-fraction approach for non-spine bone metastases in terms of pain control. Optimizing SBRT could significantly enhance the quality of life for patients by providing effective pain relief while minimizing treatment sessions., Methods: This international, multicenter phase III trial will randomize 162 patients to receive either a 3-fraction regimen (9 Gy per fraction) or a standard 5-fraction regimen (7 Gy per fraction). Outcomes, assessed at 3 months post-treatment, will focus on pain response, quality of life, and control of metastasis. With a hypothesis-driven design, the study will incorporate intent-to-treat and per-protocol analyses, incorporating appropriate measures for data integrity and handling of missing information., Discussion: If the 3-fraction SBRT regimen demonstrates non-inferiority, it could streamline palliative care protocols, reduce patient burden, and set a new standard for treatment, reflecting a patient-centered approach in palliative radiation oncology., Trial Registration: The trial has been registered prospectively on ClinicalTrials.gov under the identifier NCT05406063, as of May 3, 2022., Competing Interests: Declarations Ethics approval and consent to participate {24} Ethics approval has been obtained from Ethics Committee Zurich (BASEC2022 – 0063) and Bern. All methods are carried out in accordance with the current version of the World Medical Association Declaration of Helsinki and ICH-GCP guidelines as well as the local legally applicable requirements. All individual study participants will provide written informed consent to participate in the study. Consent will be obtained by study investigators in conjunction with clinical trials staff. Consent for publication {32} Not applicable—no identifying images or other personal or clinical details of participants are presented here or will be presented in reports of the trial results. The participant information materials and informed consent form are available from the corresponding author on request. Competing interests {28} The authors declare no competing interests., (© 2024. The Author(s).)

Background: Lateral epicondylitis impacts 1-3% of the population. It affects nearly half of all tennis players, primarily due to repetitive forearm muscle use leading to pain at the lateral elbow, particularly at the extensor carpi radialis brevis tendon. While conservative treatments resolve most cases, 4-11% of patients with persistent pain require surgery. Tenotomy is the gold standard for repair, but the research comparing the benefits of specific types of tenotomies (open, arthroscopic, percutaneous, ultrasonically assisted, and Tenex forms) is lacking. Methods: PubMed and Embase searches were conducted for articles focused on four tenotomy techniques. The inclusion criteria allowed for the use of randomized controlled trials (RCTs), prospective cohort studies, and comparative observational studies, while the exclusion criteria excluded meta-analyses. Following the PRISMA guidelines, the initial search resulted in 2327 articles. Once the inclusion and exclusion criteria were applied, 1702 articles underwent abstract screening. Finally, 232 articles proceeded to full-text screening, resulting in 37 articles undergoing data extraction. Results: The primary outcomes included functional improvement, pain relief, overall performance, and postoperative disability. The secondary outcomes included patient-reported satisfaction, return-to-work timeframes, and procedural complications. Conclusions: The tenotomy outcomes were similar, regardless of the method, indicating that discussions with patients about their specific outcome preferences may help guide tenotomy method selection.

Higher employment ratios can affect opioid use through two main channels: by increasing physical pain from working or by reducing mental distress that may contribute to substance misuse. To separate these channels, I contrast the effect of labor demand shocks on the use of opioids with the effect on the use of over-the-counter painkillers-commonly used to treat pain but not mental distress. I find that during local economic expansions, opioid use declines while the demand for over-the-counter pain relief medication increases. Employment changes in high injury industries accentuate this pattern. One possible explanation is that, during local economic expansions, the use of pain medications to manage work injuries increases while the misuse of opioids decreases., (© 2024 John Wiley & Sons Ltd.)

Osteoarthritis (OA) is a type of highly prevalent heterogeneous degenerative disease that leads to joint pain, deformity, the destruction of articular cartilage, and eventual disability. The current treatment strategies for OA often suffer from systemic side effects, poor anti-inflammatory efficacy, and persistent pain. To address these issues, we develop light-inducible nanomedicine that enables the co-delivery of anti-inflammatory drug (diacerein, DIA) and small interfering RNA (siRNA) targeting nerve growth factor (NGF) for pain relief to enhance the therapeutic efficacy of OA. The nanomedicine is based on poly( β -amino-ester)-coated gold nanocages (AuNCs), which is further incorporated with the phase-change material (lauric acid/stearic acid, LA/SA). Following intra-articular (IA) injection in vivo , the nanomedicine displays high degree of drug accumulation and retention in the joint lesion of OA mouse models. The photothermal effect, induced by AuNCs, not only promotes DIA and siRNA release, but also upregulates the expression of heat shock protein 70 (HSP-70) to resist the apoptosis of chondrocytes in the inflammatory condition. The internalization of both DIA and siRNA results in strong anti-inflammatory and pain-relieving effects, which greatly contribute to the joint repair of OA mice. This study offers a promising combination strategy for OA treatment., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Authors.)

Background: Recently, enhanced recovery after surgery (ERAS) protocols have attracted attention; they emphasize on avoiding intraoperative hypothermia while performing lumbar fusion surgery. However, none of the studies have reported the protocol for determining the temperature of saline irrigation during biportal endoscopic spine surgery (BESS) procedure. This study evaluated the effectiveness of warm saline irrigation during BESS in acute postoperative pain and inflammatory reactions., Materials and Methods: Fifty-five patients who underwent BESS procedure were retrospectively analyzed for the incidence of perioperative hypothermia (< 36 o C), postoperative inflammatory factors (white blood cells (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-6 (IL-6), serum amyloid A (SAA)), and clinical outcomes (back visual analog scale (VAS) score, postoperative shivering). The patients were divided into the warm and cold saline irrigation groups., Results: Hemoglobin, WBC, ESR, creatine kinase, and creatine kinase-muscle brain levels did not significantly differ between the warm and cold saline groups. The mean CRP, IL-6, and SAA levels were significantly higher in the cold saline group than in the warm saline group (p = 0.0058, 0.0028, and 0.0246, respectively); back VAS scores were also higher with a statistically significant difference until two days postoperatively (p < 0.001). During the entire procedure, the body temperature was significantly lower in the cold saline irrigation group, but the hypothermia incidence rate significantly differed 30 min after the operation was started., Conclusions: Using warm saline irrigation during BESS is beneficial for early recovery after surgery, as it is associated with reduced postoperative pain and complication rates., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The International Classification of Headache Disorders (ICHD-3) uses moderate or severe pain intensity in the diagnostic criterion for migraine. However, few studies have analyzed pain rating on a visual analog scale to identify the numerical intensity that correlates with migraine., Objective: To evaluate the impact of daily self-rated headache pain among patients with either episodic or chronic migraine. This study specifically aims to evaluate the probability of patients labeling their head pain as a headache vs. migraine based on the pain level reported., Methods: A retrospective chart review was conducted on patients with a clinical diagnosis of migraine from July 1, 2014, to July 1, 2019., Results: Data of 114 subjects (57 episodic migraine and 57 chronic migraine) were used for analysis. Patients with episodic migraine on average rated a migraine more severe than a headache (4.1 vs. 6.4; p < 0.001). Patients with chronic migraine on average also rated migraine more severe than a headache (4.3 vs. 6.8; p = 0.0054). Chronic migraine patients transitioned from calling head pain a headache to a migraine significantly later than episodic migraine patients (4.5 vs. 6.8; p < 0.05)., Conclusion: A migraine is perceived as having higher pain intensity than a headache in patients with both episodic and chronic migraine. On average, patients with chronic migraine had a higher pain rating at which they report head pain to be considered a migraine., (© 2024. The Author(s).)

Background and Objectives: Trigeminal Neuralgia (TN) is a debilitating facial pain disorder, often necessitating surgical interventions when medication proves insufficient. Stereotactic Radiosurgery (SRS) is an established therapeutic option. Limited studies explored the feasibility of a third SRS procedure. Our study investigates the safety and efficacy of a third SRS procedure for recurrent TN., Methods: We performed a retrospective analysis across multiple centers using databases collected prospectively. Pain status was evaluated utilizing the BNI Pain Intensity Scales. The Kaplan-Meier method was employed to estimate the time to recurrence, with group comparisons conducted using log-rank tests. Associations were explored using Chi-square and logistic regression models., Results: Ten institutions contributed with a total of 35 patients. A third SRS revealed sustained effectiveness with a pain control rate of 82.7%. The median time to recurrence was 35.5 months. New sensory dysfunction following the third procedure occurred in 22% of patients who had preserved sensory function after the second procedure. When considering those who developed sensory dysfunction after the second procedure, 40% of the entire cohort was affected. There were no significant differences in pain recurrence intervals among the three procedures. A meta-analysis, combining data from previous studies, showed that 89.6% of patients achieved some degree of pain control after a third SRS, with 27.4% experiencing new sensory dysfunction and a median time to recurrence of 31.6 months., Conclusion: Our study, the largest on the topic, affirms the sustained effectiveness of a third SRS for TN, providing comparable pain relief to initial procedures. Notably, an extended pain-free interval after the third SRS session was observed. Facial sensory dysfunction emerged as the primary side effect. Larger studies are warranted to explore correlations with demographics and treatment parameters for a comprehensive understanding of repeat SRS in managing recurrent TN., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background: Osteoporotic vertebral compression fractures (OVCF) severely affect the quality of life in the aged population. Percutaneous vertebroplasty (PVP) alleviates pain and stabilizes vertebrae, but suboptimal bone cement distribution can cause complications. Hence, this study aimed to clarify whether a new technique for PVP, using a curved guide wire, enhances the distribution of bone cement and improves clinical outcomes in patients with OVCF., Methods: Patients with single-segment OVCF underwent PVP or curved guide wire percutaneous vertebroplasty (C-PVP). Propensity score matching (PSM) was employed to balanced the baseline characteristics. The primary outcomes were the visual analog scale (VAS) and Oswestry disability index (ODI) scores. The secondary outcomes included assessments of bone cement distribution, bone cement injection volume, radiological parameters, and general clinical results. Additionally, Complications and adverse events were documented., Results: After PSM analysis, each group comprised 54 patients, which significantly reduced baseline differences. The C-PVP group showed better clinical outcomes compared to the traditional PVP group. One month after surgery, the C-PVP group had significantly lower VAS and ODI scores (p < 0.001). These improvements persisted at six months and the final follow-up. Additionally, bone cement distribution scores were better (p < 0.001), injection volume was higher (p = 0.03), leakage was less frequent (p = 0.02), and adjacent vertebral fractures occurred less frequently (p = 0.04) in the C-PVP group. Radiological parameters and overall clinical outcomes revealed no significant differences between the two groups., Conclusion: The use of curved guide wire in PVP significantly improves bone cement distribution and injection volume, resulting in better clinical efficacy in patients with OVCF., (© 2024. The Author(s).)