Pain and Therapy最新文献

Introduction: This review aimed to investigate the inadvertent administration of antibiotics via epidural and intrathecal routes. The secondary objective was to identify the contributing human and systemic factors.

Methods: PubMed, Scopus and Google Scholar databases were searched for the last five decades (1973-2023). The author recorded the antibiotics involved, the route of administration, clinical details and consequences in a standardised format. The author utilized the Human Factors Analysis Classification System (HFACS) framework to identify contributing factors.

Results: Twenty publications reported neuraxial administration of antibiotics (adults, 19, paediatric, three patients). Fifteen (of 22) incidents happened in the post-surgical or post-chronic pain procedure period. Most errors (14 of 22) occurred via the epidural route. Cefazolin (six) and gentamicin (five) were the most common among 13 antibiotics involved. Intrathecal cephalosporin incidents (n = 6) were associated with devastating consequences (death, one, permanent residual neurological deficits, three). In the unsafe act category of the HFACS, the perceptual error contributing to occurrences of neuraxial antibiotics administration errors was due to IV-neuraxial device (e.g. intrathecal drain or catheter, epidural catheter) confusion (eight patients) or syringe/infusion bag swap (nine patients).

Conclusions: Intrathecal cephalosporins and gentamicin administration are associated with devastating consequences. Prevention of neuraxial antibiotic administration requires improvements in clinical deficiencies and the implementation of supporting technological tools to prepare and administer antibiotics correctly, thereby ensuring patient safety.

Introduction: There is a high unmet need for safe and effective non-opioid medicines to treat moderate to severe pain without risk of addiction. Voltage-gated sodium channel 1.8 (Na_V1.8) is a genetically and pharmacologically validated pain target that is selectively expressed in peripheral pain-sensing neurons and not in the central nervous system (CNS). Suzetrigine (VX-548) is a potent and selective inhibitor of Na_V1.8, which has demonstrated clinical efficacy and safety in multiple acute pain studies. Our study was designed to characterize the mechanism of action of suzetrigine and assess both nonclinical and clinical data to test the hypothesis that selective Na_V1.8 inhibition translates into clinical efficacy and safety, including lack of addictive potential.

Methods: Preclinical pharmacology and mechanism of action studies were performed in vitro using electrophysiology and radiolabeled binding methods in cells recombinantly expressing human Na_V channels, human proteins, and primary human dorsal root ganglion (DRG) sensory neurons. Safety and addictive potential assessments included in vitro secondary pharmacology studies, nonclinical repeat-dose toxicity and dependence studies in rats and/or monkeys, and a systematic analysis of adverse event data generated from 2447 participants from phase 3 acute pain studies of suzetrigine.

Results: Suzetrigine is selective against all other Na_V subtypes (≥ 31,000-fold) and 180 other molecular targets. Suzetrigine inhibits Na_V1.8 by binding to the protein's second voltage sensing domain (VSD2) to stabilize the closed state of the channel. This novel allosteric mechanism results in tonic inhibition of Na_V1.8 and reduces pain signals in primary human DRG sensory neurons. Nonclinical and clinical safety assessments with suzetrigine demonstrate no adverse CNS, cardiovascular or behavioral effects and no evidence of addictive potential or dependence.

Conclusions: The comprehensive pharmacology assessment presented here indicates that suzetrigine represents the first in a new class of non-opioid analgesics that are selective Na_V1.8 pain signal inhibitors acting in the peripheral nervous system to safely treat pain without addictive potential.

Background: Children under the age of 3 years have been diagnosed with complex regional pain syndrome (CRPS). They were found to be functionally disadvantaged and psychologically distressed in relation to children with other painful conditions.

Case presentation: An 18-month-old baby girl was referred to the pain clinic with a history of severe right lower limb pain that had begun 2 months earlier. The parents were unable to recall any trauma before the painful situation. Pain and allodynia were severe and extended from the toes to the gluteus area. She was low weight for her age (6700 g). The patient was on the maximum doses of gabapentin and amitriptyline accepted for her body weight and did not have the possibility to start rehabilitation due to severe pain and allodynia. After discussing the risks and potential benefits of a planned lumbar sympathetic block (LSB), the parents approved the interventional procedure. This is the first case report describing the LSB technique at such a young age.

Method: A lumbar sympathetic block was carried on at the third lumbar vertebral level, fluoroscopy-guided, and under general anesthesia (GA) initiated with ketamine iv. A 4-cm needle was introduced using a tunneled vision approach in an oblique view at the L3 level until adequate depth was confirmed in the lateral position. Safety considerations were taken in relation to the radiation dose and all drugs injected with dose adjustment to her body weight. The block was successful (the skin temperature increased by 2.8 °C) and was uneventful. Pain and allodynia were completely alleviated in the recovery room. At the follow-up after 3 and 8 weeks, the parents reported an 80% improvement in pain and allodynia, a 70% improvement in sleep, a weight gain of 900 g, and that she had started rehabilitation.

Conclusions: Lumbar sympathetic blocks can be considered at a very young age to treat CRPS if other non-invasive measures fail.

Introduction: Critically ill patients often endure pain, a distressing experience that can trigger diverse pathophysiological consequences. While remifentanil, with its rapid kinetics, is commonly used for analgesia in intensive care units (ICU), it frequently leads to opioid-related adverse effects. A promising alternative has emerged in oliceridine, a novel G protein-biased μ-opioid receptor agonist. This new drug offers the potential for effective pain relief with fewer side effects. However, its efficacy and safety profile in mechanically ventilated ICU patients remain to be fully elucidated.

Methods: This is a multicenter, prospective, randomized, single-blind, active-controlled trial conducted across 24 ICUs in China. A total of 292 mechanically ventilated patients requiring analgesia and sedation will be randomly assigned in a 1:1 ratio to either the oliceridine or remifentanil group. The oliceridine group will receive oliceridine (2-20 μg/kg/h), while the remifentanil group will receive remifentanil (1.5-12 μg/kg/h). Both groups will receive propofol for sedation if necessary. The target for analgesia is Critical-Care Pain Observation Tool (CPOT) < 3, and for sedation is Richmond Agitation-Sedation Scale (RASS) - 2 to 0.

Planned outcomes: The primary outcome will be the percentage of time within target analgesia during study drug administration. Secondary outcomes will include gastrointestinal dysfunction, respiratory depression, sedative usage, mechanical ventilation duration, ICU stay length, extubation failure rate, etc. TRIAL REGISTRATION: NCT06454292. Registered on June 11, 2024.

In recent decades, cranial and cervical vascular disorders have become major global health concerns, significantly impacting patients, families, and societies. Headache is a prevalent symptom of these vascular diseases and can often be the initial, primary, or sole manifestation. The intricate relationship between headaches and cranial/cervical vascular disorders poses a diagnostic and therapeutic challenge, with the underlying mechanisms remaining largely elusive. Understanding this association is crucial for the early diagnosis, prevention, and intervention of such conditions. This review aims to provide a comprehensive overview of the clinical features and potential pathogenesis of headaches attributed to cranial and cervical vascular disorders and provide a reference for disease management and a basis for potential pathological mechanisms.

Introduction: Methadone has shown effectiveness in pain control in patients with cancer who are intolerant to other opioids in China. However, the optimal strategy for methadone conversion from previous high doses of opioids in refractory cancer pain remains debatable. This study aimed to describe the efficacy and safety of a 3-day switch (3DS) strategy for methadone conversion in patients with refractory cancer pain on high doses of opioids.

Methods: We retrospectively reviewed 30-day medical records of 70 patients with refractory cancer pain who used a 3DS strategy for methadone conversion from previous high doses of opioids from July 2018 to December 2022. The 3DS strategy indicated that the methadone dose was increased by one third every day for 3 days. Data on the rate of successful conversion, the time to stable analgesia after conversion, the conversion efficiency, the corrected QT (QTc) interval, the actual conversion ratios, adverse events (AEs), and quality of life were analyzed.

Results: Seventy patients received 3DS methadone conversion and 64 patients were eligible for analysis. Fifty patients (78%) achieved stable analgesia, and the median time to stable analgesia was 8.14 ± 2.70 (range 6-14) days. The average dose of methadone was 77.94 ± 42.74 mg. The most common AEs (≥ 10%) included constipation, dry mouth, nausea, and cold sweats. The incidence of constipation was reduced post-methadone conversion, and a statistically significant but asymptomatic prolongation of the QTc interval was observed. Additionally, the actual conversion ratios were lower than Ayonrinde's recommended ratios.

Conclusions: The 3DS strategy for methadone conversion is applicable in Chinese patients with refractory cancer pain on high doses of opioids.

Introduction: There is a multitude of evidence supporting the use of manual and manipulative therapy techniques for patients with cervicogenic headache (CGH). However, evidence in finding and comparing the efficacy of instrument assisted soft tissue mobilization with manual therapy in unilateral cervicogenic headache is lacking. Therefore, the objective of the study is to find and compare the long term effects of instrument assisted soft tissue mobilization along with spinal manipulation therapy in patients with cervicogenic headache.

Methods: It is a randomized, single-blinded controlled study conducted at University hospital. Overall, 64 participants with CGH were divided into spinal manipulation therapy group (SMT; n = 32) and spinal manipulation therapy with instrument assisted soft tissue mobilization (ISM) group (SMT + ISM; n = 32) and they received the respective treatment for 4 weeks. In addition, both groups received 10 min of heat therapy and neck isometric exercises three times a day. The primary (CGH frequency) and secondary (CGH pain intensity, CGH disability neck pain frequency, pain intensity, pain threshold, neck disability index and quality of life) scores were measured at baseline, after 4 weeks, and at 6 months.

Results: The reports of the SMT and SMT + ISM group were compared. Following 4 weeks of training, and at 6 months follow up the SMT + ISM group showed more significant changes in the primary outcome (CGH frequency) with a -4.3 [(95% confidence interval (CI) -4.80 to -3.79] and -1.7 (95% CI -1.92 to -1.47), when compared with the SMT group alone (p = 0.001). The secondary outcomes (CGH pain intensity, CGH disability, neck pain frequency, neck pain intensity, neck disability index, and quality of life) also shows more significant changes in the SMT + ISM group than the SMT group (p = 0.001). The same gradual improvement can be seen in the above variables at 6 months follow up. At the same time, neck pain threshold level does not show any improvement at 4 weeks (p ≥ 0.05) but shows a statistical difference at 6 months follow up. No such adverse effects or consequences were noted during or after the intervention.

Conclusions: The study concluded that spinal manipulation therapy with instrument assisted soft tissue mobilization provided better long-term outcomes in patients with cervicogenic headache. This study provided a piece of sound physical therapy evidence for a widespread and costly clinical condition, such as cervicogenic headache.

Clinical trial registration: The trial was registered prospectively in the Indian clinical trial registry with CTRI/2020/06/026243 on 30/06/2020.

Introduction: The purpose of this systematic review and network meta-analysis was to evaluate the efficacy and safety of different preemptive analgesia measures given before laparoscopic cholecystectomy (LC) for postoperative pain in patients.

Methods: We conducted a comprehensive search in databases including PubMed, Web of Science, Embase, and the Cochrane Library up to March 2024, and collected relevant research data on the 26 preemptive analgesia measures defined in this article in LC surgery. Outcomes included postoperative Visual Analogue Scores (VAS) at different times (2, 6, 12, and 24 h), opioid consumption within 24 h post-operation, time to first rescue analgesia, incidence of postoperative nausea and vomiting (PONV), and incidence of postoperative headache or dizziness.

Results: Forty-nine articles involving 5987 patients were included. The network meta-analysis revealed that multimodal analgesia, nerve blocks, pregabalin, and gabapentin significantly reduced postoperative pain scores at all postoperative time points and postoperative opioid consumption compared to placebo. Tramadol, pregabalin, and gabapentin significantly extended the time to first rescue analgesia. Ibuprofen was the best intervention for reducing PONV incidence. Tramadol significantly reduced the incidence of postoperative headache or dizziness. Subgroup analysis of different doses of pregabalin and gabapentin showed that compared to placebo, pregabalin (300 mg, 150 mg) and gabapentin (600 mg, 300 mg, and 20 mg/kg) were all more effective without significant differences in efficacy between these doses. Higher doses increased the incidence of PONV and postoperative headache and dizziness, with gabapentin 300 mg having a lower adverse drug reaction (ADR) incidence.

Conclusions: Preemptive analgesia significantly reduced postoperative pain intensity, opioid consumption, extended the time to first rescue analgesia, and decreased the incidence of PONV and postoperative headache and dizziness. Multimodal analgesia, nerve blocks, pregabalin, and gabapentin all showed good efficacy. Gabapentin 300 mg given preoperatively significantly reduced postoperative pain and ADR incidence, recommended for preemptive analgesia in LC.

Trial registration: PROSPERO CRD42024522185.

Introduction: Multi-modal analgesia is desirable for the management of acute pain since it can provide effective pain relief at lower doses, thereby aiding tolerability. Co-crystal of tramadol-celecoxib (CTC) provides effective analgesia in models of acute pain. Co-crystallization can alter the pharmacokinetics of individual components, potentially improving tolerability. We sought to better understand the safety and tolerability of CTC in patients with acute postoperative pain.

Methods: We conducted a pooled analysis of safety data from three phase 3 randomized controlled trials in adults with acute moderate-to-severe pain following oral surgery, bunionectomy, and elective abdominal hysterectomy. We present data for CTC 200 mg twice daily (BID) and its comparators: tramadol 50 mg four times daily (QID) (one trial), tramadol 100 mg QID (two trials), celecoxib 100 mg BID (two trials), and placebo (three trials).

Results: In total, n = 551 patients received CTC 200 mg BID, n = 183 received tramadol 50 mg QID, n = 368 received tramadol 100 mg QID, n = 388 received celecoxib 100 mg BID, and n = 274 received placebo. The prevalence of adverse events (AEs) related to study drug up to 48 h was numerically lower with CTC 200 mg BID (35.9%) than with tramadol 50 mg QID (47.5%) and 100 mg QID (44.8%) but greater than with celecoxib 100 mg BID (12.4%) and placebo (20.4%). The most frequent AEs related to study drug up to 48 h were somnolence, nausea, dizziness, and vomiting, which occurred more frequently in patients receiving tramadol 100 mg QID than in those receiving CTC 200 mg BID.

Conclusion: CTC 200 mg BID appears to be better tolerated than tramadol 100 mg QID, possibly because of reduced total exposure to tramadol. This may contribute to a more favorable benefit-risk profile for CTC versus individual components, making it a promising treatment for acute pain.

Trial registration: ClinicalTrials.gov identifiers: NCT03108482, NCT02982161 (EudraCT: 2016-000592-24), NCT03062644 (EudraCT: 2016-000593-38).