Analgesia For Pain Research Articles

Pain management in elective major gynaecology surgery: implementing an enhanced recovery protocol

Background: Enhanced recovery after surgery (ERAS) improves outcomes in major surgery.1 Optimising analgesia with a multimodal, opioid-sparing approach allows for faster recovery, reducing hospital stay, costs, and morbidity.2 We implemented a perioperative enhanced recovery protocol (ERP) in elective major gynaecological surgery and analysed its impact on pain scores, side-effects and return to baseline function. Methods: Pre-ERP implementation data were collected from December 2020 to June 2021. Post-ERP data were collected from September to December 2021. Elective gynaecology lists were screened for eligible patients (>18 yr, hysterectomy or myomectomy, open or laparoscopic). Data were prospectively collected using dedicated questionnaires (anaesthetic technique, postoperative analgesic requirement, pain scores, side-effects, and return to baseline). Results: Comparison of 37 patients pre-ERP and 25 patients post-ERP respectively revealed: (1) low pain score (<3/10) on day 1 postoperatively at rest (54% vs 64%), coughing (18% vs 28%) and moving (8% vs 24%), (2) experiencing side-effects: nausea (27% vs 12%), pruritis (16% vs 12%), drowsiness (19% vs 4%), and (3) return to baseline function: ambulating by Day 1 (76% vs 88%), oral intake by Day 1 (92% vs 100%) and discharged by Day 2 (75% vs 84%). Conclusions: After ERP implementation, patients were more likely to report lower pain scores, despite lower average opioid use, and less likely to report associated side-effects (nausea, itching, and drowsiness). Patients were also more likely to be ambulating and eating by Day 1 postoperatively and discharged by Day 2. These results highlight clinical and, potentially, cost-saving improvements. The authors sincerely thank the anaesthetic, recovery, and pain teams at Whipps Cross Hospital. Approval was obtained from the clinical governance department. 1.Patil S, Cornett EM, Jesunathadas J, et al. J Anaesthesiol Clin Pharmacol 2019; 35: S24–82.Bisch SP, Kooy J, Glaze S, et al. Int J Gynecol Cancer 2019; 29; 1372–6

Acupuncture as Part of Multimodal Analgesia for Chronic Pain.

Chronic pain is a multifactorial condition that is afflicting populations worldwide causing an increasing economic, physical, mental, and emotional burden. Treatments range from medications to interventional procedures to complementary and alternative medicine (CAM), such as acupuncture. This review aims to discuss the use of acupuncture in the treatment of chronic pain, proposed mechanisms, indications, and efficacy for various chronic pain conditions. Evidence is varied on the efficacy and quality of data on the use of acupuncture in the treatment of chronic pain. Recent studies have demonstrated promising results in the support of acupuncture for the use in the treatment of cancer, neck, and back pain, functional dyspepsia, and various chronic abdominal pain syndromes. Acupuncture, deemed well-tolerated and safe to use, has been increasingly studied and is regarded as effective in clinical practice, but its efficacy is limited by the lack of well-conducted, high-quality clinical trials, lower quality evidence, and conflicting study results. Additionally, the exact analgesic mechanism of acupuncture remains to be fully elucidated. Increasing evidence supports the role of acupuncture as therapy in the treatment of cancer, neck, and back pain and functional dyspepsia. Further rigorous studies are needed to fully assess the use of acupuncture in various chronic pain conditions, determine its indications, and optimal treatment schedule. Overall, future studies could benefit from better designed experimental studies, larger groups, and more objectives ways to measure pain reduction and symptom improvement.

Paravertebral vs. Epidural Analgesia for Liver Surgery (PEALS): Protocol for a randomized controlled pilot study

Background: Perioperative thoracic epidural analgesia (TEA) is commonly used in hepatectomy patients since it is opioid-sparing and reduces cardiorespiratory complications. However, TEA has a high failure rate and is associated with potentially devastating complications (particularly spinal haematoma) and the risk is likely increased with hepatectomy. Thus, some centres favour systemic opioid-based modalities which, in turn, are associated with inferior analgesia and well-known risks/side-effects. Hence, alternative analgesic methods are desirable. Paravertebral block (PVB) has been used in liver resection with advantages including hemodynamic stability, low failure rates, and low risk of spinal haematoma. Our purpose is to conduct a blinded, pilot RCT with hepatectomy patients randomised to receive TEA or PVB for perioperative analgesia. Our hypothesis is that opioid consumption, time to first analgesic request, and pain scores will be comparable between groups, but PVB patients will require fewer perioperative vasopressors/blood products, and have fewer adverse events and a shorter hospital stay. Methods: With ethics approval, this non-inferiority, pilot RCT with a convenience sample of 50 hepatectomy patients will examine whether PVB imparts analgesia comparable to TEA but with fewer adverse effects. Primary outcomes are surrogates of analgesia for 72 h postoperatively (i.e., opioid consumption, time to first analgesic request and pain scores at rest and with coughing); Secondary outcomes are blood products/fluids administered; side effects/complications until 72 h postoperatively; length of hospital stay. The results will be used to plan a large multicentre trial comparing TEA vs. PVB in hepatectomy patients. This study has a high potential to positively impact the quality/safety of patient care. ClinicalTrials.gov registration: NCT02909322 (09-21-2016); Available at URL: https://clinicaltrials.gov/ct2/show/NCT0290932

Antagonism of the orexin receptors in the ventral tegmental area diminished the stress-induced analgesia in persistent inflammatory pain

As a part of descending pain inhibitory system, orexin (OXs) in the ventral tegmental area (VTA) are implicated in nociceptive responses. The current study aimed to evaluate the role of OX receptors (OXRs) in the VTA in stress-induced analgesia in persistent inflammatory pain. Ninety-nine adult male Wistar rats underwent forced swim stress (FSS) following intra-VTA infusion of various doses of SB334867 or TCS OX2 29 (1, 3, 10, and 30 nmol/0.3 μL) as an OX1R or OX2R antagonist, respectively. The nociceptive threshold was evaluated using the formalin test as an animal model of persistent inflammatory pain. Current results demonstrated FSS as acute stress produced analgesic responses in the persistent inflammatory pain. Moreover, either OX1R or OX2R antagonist infusion in the VTA hindered the FSS-induced analgesia in both early and late phases. The inhibitory effect of SB334768 in the FSS-induced analgesia was stronger than TCS OX2 29 in both early and late phases of the formalin test. Neither SB334768 nor TCS OX2 29 alone affects pain-related behaviors in formalin tests. Intra-VTA microinjection of each treatment could not modify locomotion in rats. The findings suggest that OX1R and OX2R in the VTA are implicated in FSS-induced analgesia mechanisms.

End-of-life offerings in US medical schools: 1975-2020

ABSTRACT Forty-five years ago, the first author of this paper surveyed the US medical schools to determine their offerings on EOL (End-of-Life) issues. The results showed limited exposure for medical school students to learn about dying and death, thus their “learning” was apparently on-the-job training. The EOL offerings were so limited that the American Association of Medical Colleges (AAMC), following the 1975 publication from the survey, contacted the first author to inquire about death and dying in the curricula of their medical schools. Apparently, it was so insignificant that the AAMC did not have such information. Palliative medicine, geriatric medicine, and hospice were then in the “birthing” process, a mere blur on the horizon. Today, as in 1975, it is likely that most medical students have personally had minimal experience with death and that for many entering students, other than on television, the cadaver is their first sight of a dead person. The objective of this research is a longitudinal study at five-year intervals since 1975 reporting on EOL education in US medical schools. The total number of medical schools has increased from 113 in 1975 to 150 in 2020. The current study surveyed medical schools electronically and via postal services with a response rate of 37%. Findings from the survey over time revealed significant inclusion of death and dying and palliative medicine as well as geriatrics and hospice. Gross anatomy has evolved from strictly hands-on to integrating 3D/virtual models, a change not without controversy. A noticeable difference in emphasis is obvious as care now plays a more significant role in medical training than previously, thus making modern medicine not only about cure, but more about care than was previously emphasized. Communication with dying patients and families, analgesics for chronic pain, and advance directives all are covered in over 90% of schools today. The current emphasis on EOL care, not just disease management, is increasing and puts more of a human face on modern medicine.

The Effect of Pre-emptive Oral Melatonin versus Placebo on Post-operative Analgesia in Infants after Thoracotomy for Closed Cardiac Surgeries: A Randomized Controlled Study

BACKGROUND: Thoracotomy pain is one of the severest types of pain that should be managed properly, especially in children. Opioids are the most widely prescribed analgesics for post-operative pain, but they can have a number of undesirable side effects. Melatonin could be employed as an adjuvant analgesic therapy during procedural discomfort as it had no known major side effects. STUDY DESIGN: This was a double-blinded, controlled randomized study. METHODS: Fifty patients divided randomly into two equal groups. One hour before surgery, children in M group (n = 25) were given 0.5 mg/kg orally of melatonin 3 mg tablets) and patients in Group P (n = 25) received a placebo (5 ml of water by syringe 5 ml) orally. Post-operative pethidine consumption over the 1st 24 h (mg) was recorded, the intraoperative fentanyl consumption (HR and ABP) at baseline, 1 min after induction, at skin incision, and every 30 min till the end of the surgery were recorded. Neonatal Infant Pain Score (NIPS) at 4 h, 6 h, 8 h, 12 h, 18 h, and 24 h postoperatively was recorded. Other reported data include demographic data, extubation time, days of ICU stay, and complications. RESULTS: Total post-operative pethidine consumption (mg) over 24 h was significantly lower in M group than P group (3.48 ± 2.23 vs. 7.68 ± 4.52 p = 0.01). Intraoperative fentanyl consumption (ug) was significantly lower in M group than P group (10.28 ± 4.98 vs. 17.08 ± 7.39 p &lt; 0.001). As regards NIPS, it was statistically lower in M group than P group in all times except at 8 h and 24 h with significant difference. CONCLUSION: Oral melatonin is an effective and safe pre-emptive drug as it reduces the total post-operative pethidine consumption over the first 24 h and decreased post-operative pain scores without any unpleasant effects in pediatrics undergoing closed heart surgery.

A randomized controlled trial assessing the safety and efficacy of palmitoylethanolamide for treating diabetic-related peripheral neuropathic pain

BackgroundPeripheral neuropathy is a common complication of diabetes. The management of the associated neuropathic pain remains difficult to treat.ObjectiveThis study explored the safety, tolerability and efficacy of a palmitoylethanolamide (PEA) formulation in treating diabetic-related peripheral neuropathic pain (PNP). Secondary outcomes included systemic inflammation, sleep and mood changes in patients diagnosed with type 1 and type 2 diabetes and PNP.DesignThis study was a single-centre, quadruple-blinded, placebo-controlled trial with 70 participants receiving 600 mg of PEA or placebo daily, for 8 weeks, with a 94% rate of study participation completion. Primary outcomes were neuropathic pain and specific pain types (the BPI-DPN and NPSI). The secondary outcomes were sleep quality (MOS sleep scale), mood (DASS-21), glucose metabolism and inflammation.ResultsThere was a significant reduction (P ≤ 0.001) in BPI-DPN total pain and pain interference, NPSI total score and sub-scores, except for evoked pain (P = 0.09) in the PEA group compared with the placebo group. The MOS sleep problem index and sub-scores significantly improved (P ≤ 0.001). DASS-21 depression scores significantly reduced (P = 0.03), but not anxiety or stress scores. Interleukin-6 and elevated C-reactive protein levels significantly reduced in the PEA group (P = 0.05), with no differences in fibrinogen between groups (P = 0.78) at treatment completion. There were no changes in safety pathology parameters, and the treatment was well tolerated.ConclusionsThe study demonstrated that the PEA formulation reduced diabetic peripheral neuropathic pain and inflammation along with improving mood and sleep. Further studies on the mechanistic effectiveness of PEA as an adjunct medicine and as a monotherapy pain analgesic are warranted.Clinical Trial RegistrationRegistry name: Australian New Zealand Clinical Trials Registry (ANZCTR), Registration number: ACTRN12620001302943, Registration link: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380826, Actual study start date: 20 November 2020.

Cancer-Related Bone Pain: Patients’ Satisfaction with Analgesic Pain Control

Background: Management of cancer-related bone pain (CRBP) with analgesics poses a substantial challenge. This study aimed to determine the correlation between pain control satisfaction and prescribed analgesics. Methods: This 12-month descriptive prospective study included 96 adults who were consecutively sampled and followed up daily for 5 days. Eligible patients had histopathologically confirmed tumor, osseous lesion(s) on radiographs, and cognitive capacity to rank pain on the Numerical Rating Scale. Data were collected using questionnaires drafted from the Brief Pain Inventory. Self-assessed pain scores within the past 24 hours were reported on a scale of 0 (no pain) to 10 (worst pain). Pain control satisfaction was assessed as a single response question (satisfied, not sure, or dissatisfied). Associations were examined in multiple logistic regression models. Ethical approval and informed consent were obtained. Results: The median age was 57 (range, 19–90) years, and more males (52.1%) than females were recruited. The proportion of CRBP ranged from 83.3% to 86.5%, whereas that of moderate to severe pain ranged from 57.3% to 69.8%. Overall, 70.8% were satisfied with their pain control. Patients prescribed opioids (adjusted odds ratio, 0.027; p=0.041) had an increased likelihood of pain control satisfaction. Conclusion: Although a high percentage of patients experienced moderate to severe CRBP, a majority were satisfied with their analgesic pain control. Prescription opioids were associated with higher satisfaction. Policies that sustain ready accessibility of analgesics, particularly opioids, should be implemented.

5-HT7 receptor-dependent intestinal neurite outgrowth contributes to visceral hypersensitivity in irritable bowel syndrome

AbstractIrritable bowel syndrome (IBS) is characterized by visceral hypersensitivity (VH) associated with abnormal serotonin/5-hydroxytryptamine (5-HT) metabolism and neurotrophin-dependent mucosal neurite outgrowth. The underlying mechanisms of VH remain poorly understood. We investigated the role of 5-HT7 receptor in mucosal innervation and intestinal hyperalgesia. A high density of mucosal nerve fibres stained for 5-HT7 was observed in colonoscopic biopsy specimens from IBS patients compared with those from healthy controls. Staining of 5-HT3 and 5-HT4 receptors was observed mainly in colonic epithelia with comparable levels between IBS and controls. Visceromotor responses to colorectal distension were evaluated in two mouse models, one postinfectious with Giardia and subjected to water avoidance stress (GW) and the other postinflammatory with trinitrobenzene sulfonic acid-induced colitis (PT). Increased VH was associated with higher mucosal density of 5-HT7-expressing nerve fibres and elevated neurotrophin and neurotrophin receptor levels in the GW and PT mice. The increased VH was inhibited by intraperitoneal injection of SB-269970 (a selective 5-HT7 antagonist). Peroral multiple doses of CYY1005 (a novel 5-HT7 ligand) decreased VH and reduced mucosal density of 5-HT7-expressing nerve fibres in mouse colon. Human neuroblastoma SH-SY5Y cells incubated with bacteria-free mouse colonic supernatant, 5-HT, nerve growth factor, or brain-derived neurotrophic factor exhibited nerve fibre elongation, which was inhibited by 5-HT7 antagonists. Gene silencing of HTR7 also reduced the nerve fibre length. Activation of 5-HT7 upregulated NGF and BDNF gene expression, while stimulation with neurotrophins increased the levels of tryptophan hydroxylase 2 and 5-HT7 in neurons. A positive-feedback loop was observed between serotonin and neurotrophin pathways via 5-HT7 activation to aggravate fibre elongation, whereby 5-HT3 and 5-HT4 had no roles. In conclusion, 5-HT7-dependent mucosal neurite outgrowth contributed to VH. A novel 5-HT7 antagonist could be used as peroral analgesics for IBS-related pain.

Prescription of opioid analgesics for non-cancer pain in Germany: study protocol for a mixed methods analysis

AimLong-term therapy with opioid analgesics bears the risk of complications, such as misuse, abuse, and dependence. An evidence-based guideline addresses the long-term use of opioid analgesics for non-cancer pain. Recent studies observed an increase in opioid prescriptions over the past two decades in Germany. However, the exact circumstances of this increase and if long-term therapy adheres to these guidelines in practice remains unknown. Therefore, this study aimed to evaluate the provision of opioid analgesics for adults with non-cancer pain from patients’ and physicians’ perspectives. Based on the results, recommendations for care strategies for the patient groups at risk of misuse, abuse, and dependence were developed.MethodsBuilt on a mixed methods approach, this evaluation combines (i) interviews with primary care physicians and specialists, (ii) surveys of patients and physicians, (iii) analyses based on administrative claims data from a German statutory health insurance provider. Proceeding from the analysis of the evaluation results, the development of care strategies included (iv) semi-structured interviews with stakeholders and (v) expert workshops.ConclusionTo our knowledge, this is the first attempt to analyze opioid prescriptions from the combined perspectives of patients and practitioners in Germany. The results are intended to facilitate the development of target group-specific care strategies and recommendations to establish a general framework for the implementation of care strategies.

Abdominoplasty as an acute postoperative pain model: insights from 8 years of clinical trials.

To have a complete understanding of an experimental analgesic's efficacy in treating acute postoperative pain, it is necessary to understand its effect on both hard-tissue pain and soft-tissue pain. For this reason, regulatory bodies including the U.S. Food and Drug Administration and European EMA typically require drug developers to demonstrate efficacy in both hard-tissue and soft-tissue pain to grant a broad approval for an analgesic in acute postoperative pain. Hard-tissue models such as bunionectomy and molar extraction are well-validated and efficient with long histories in clinical trials, but until recently, a similarly well-standardized and fast-enrolling soft-tissue model was not available. Abdominoplasty was developed as an acute postoperative pain model and introduced to the clinical trial marketplace in 2014 to address the need for a viable soft-tissue model. Since then, at least 13 industry-sponsored studies, including multiple pivotal trials, have been conducted, providing a data set that can be used to interrogate the model's strengths and weaknesses. The authors outline the development history of abdominoplasty, discuss key clinical and design characteristics of the model, and review public data from abdominoplasty acute pain studies available to date. The data suggest that abdominoplasty is a well-validated soft-tissue surgical model that provides high-quality experimental outputs, enabling the efficacy of investigational analgesics in soft-tissue pain to be understood successfully.

Novel N-normetazocine Derivatives with Opioid Agonist/Sigma-1 Receptor Antagonist Profile as Potential Analgesics in Inflammatory Pain.

Although opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) are the most common drugs used in persistent pain treatment; they have shown many side effects. The development of new analgesics endowed with mu opioid receptor/delta opioid receptor (MOR/DOR) activity represents a promising alternative to MOR-selective compounds. Moreover, new mechanisms, such as sigma-1 receptor (σ1R) antagonism, could be an opioid adjuvant strategy. The in vitro σ1R and σ2R profiles of previous synthesized MOR/DOR agonists (−)-2R/S-LP2 (1), (−)-2R-LP2 (2), and (−)-2S-LP2 (3) were assayed. To investigate the pivotal role of N-normetazocine stereochemistry, we also synthesized the (+)-2R/S-LP2 (7), (+)-2R-LP2 (8), and (+)-2S-LP2 (9) compounds. (−)-2R/S-LP2 (1), (−)-2R-LP2 (2), and (−)-2S-LP2 (3) compounds have Ki values for σ1R ranging between 112.72 and 182.81 nM, showing a multitarget opioid/σ1R profile. Instead, (+)-2R/S-LP2 (7), (+)-2R-LP2 (8), and (+)-2S-LP2 (9) isomers displayed a nanomolar affinity for σ1R, with significative selectivity vs. σ2R and opioid receptors. All isomers were evaluated using an in vivo formalin test. (−)-2S-LP2, at 0.7 mg/kg i.p., showed a significative and naloxone-reversed analgesic effect. The σ1R selective compound (+)-2R/S-LP2 (7), at 5.0 mg/kg i.p., decreased the second phase of the formalin test, showing an antagonist σ1R profile. The multitarget or single target profile of assayed N-normetazocine derivatives could represent a promising pharmacological strategy to enhance opioid potency and/or increase the safety margin.

Extended Release of Bupivacaine from Temperature-responsive Hydrogels Provides Multi-day Analgesia for Postoperative Pain.

A local anesthetic that provides analgesia lasting at least three days could significantly improve postoperative pain management. This study evaluated the analgesic efficacy and safety of an extended-release formulation of bupivacaine based on the injectable hydrogel carrier poly(N-isopropylacrylamide-co-dimethylbutyrolactone acrylamide-co-Jeffamine M-1000 acrylamide) (PNDJ). The efficacy of PNDJ containing 4% bupivacaine (SBG004) given by peri-incisional subcutaneous injection (SBG004 SC) or wound filling instillation (SBG004 WF) was evaluated compared to saline, liposomal bupivacaine, bupivacaine collagen sponge, bupivacaine-meloxicam polyorthoester, and bupivacaine HCl in a porcine skin and muscle incision model. Mechanical allodynia was assessed by withdrawal from application of von Frey filaments, and local tolerance was evaluated by histology. Bupivacaine pharmacokinetics for SBG004 SC were measured in rabbits (16.5 mg bupivacaine/kg). Animals demonstrated less mechanical allodynia at incisions receiving SBG004 SC for up to 96 hours postoperatively. Incisions treated with SBG004 SC tolerated more force without a withdrawal indicative of pain compared to saline for 96 hours, and compared to SBG004 WF and all active controls at 24, 48, and 72 hours except bupivacaine-meloxicam polyorthoester at 72 hours. By 49 days, SBG004 was histologically absent and was replaced with granulation tissue infiltrated with immune cells in some areas. In rabbits, Cmax was 41.6 ± 9.7 ng/mL with t1/2 82.0 ± 35.8 hours (mean ± SD). Peri-incisional SBG004 SC provided extended release of bupivacaine sufficient to reduce sensation of incisional pain for 96 hours, in vivo bupivacaine delivery for at least 7 days, and a favorable local and systemic toxicity profile.

Anesthetic and analgesic techniques used for dogs undergoing ovariohysterectomies in general practice in the United States

ObjectiveTo acquire information about anesthesia and analgesia protocols used by United States (US) veterinarians in primary care practices when performing routine ovariohysterectomy in dogs. Study designCross-sectional survey. PopulationPrimary care veterinarians in the US. MethodsAn online anonymous survey, originally created in New Zealand, was modified with permission and made available to Veterinary Information Network (VIN) members. The survey asked questions about performing ovariohysterectomy in healthy adolescent dogs in the categories of preanesthetic evaluation, premedication and induction protocols, maintenance protocols and monitoring equipment, and postoperative analgesic and sedation protocols and pain assessments. ResultsA total of 1213 US veterinarians completed the survey. Respondents (n; %) reported performing preoperative laboratory tests [packed cell volume (135; 11%), complete blood cell count (889; 73%) and biochemistry panels (1057; 87%)] and preanesthetic examinations on the morning of surgery (1083; 90%). The most commonly administered drugs for premedication were acepromazine (512; 42%), hydromorphone (475; 39%) or butorphanol (463; 38%), with propofol (637; 67%) for induction of anesthesia and isoflurane (882; 73%) for maintenance of anesthesia. Most veterinarians reported placing intravenous catheters (945; 78%), administering electrolyte solutions (747; 67%) and providing heat support (1160; 96%). Perioperative and postoperative analgesia included local anesthetics (545; 45%), opioids (844; 70%) and non-steroidal anti-inflammatory drugs (NSAIDs) (953; 79%); NSAIDs were dispensed for home use (985; 81%). Dogs were most frequently discharged on the day of surgery (1068; 88%) and the owners were contacted (914; 75%) for follow-up within 1–2 days. Conclusions and clinical relevanceAnesthetic management for routine ovariohysterectomy in dogs varies among US veterinary VIN members. Information from this study is useful for all veterinarians for comparison with their practice management and for teachers of veterinary anesthesia to continue to emphasize options for analgesia.

Are Pain Screening and Functional Assessment Results Associated with New Diagnoses and Treatment for Pain in Primary Care? An Observational Study

PurposeTo determine if pain screening and functional assessment results are associated with new diagnoses and treatment for pain in primary care.Patients and MethodsObservational study at 13 primary care sites of a statewide federally qualified health center that implemented routine screening and functional assessment for all adults in primary care. The study group included 10,091 adults aged 18+ who had an in-person visit between July 2, 2018, and June 1, 2019, where they screened positive for chronic pain and completed a 3-question functional assessment with the PEG (Pain, Enjoyment of Life, General Activity). Multivariate logistic regressions quantified associations between pain frequency, diagnosis and treatment, sociodemographics, comorbidities, and self-reported severe pain impairment with pain diagnoses and treatment documented after screening.ResultsPatients were mostly women (60.3%), Latinx (41.1%), English-speaking (80.1%), and Medicaid-insured (62.0%); they averaged 49.1 years old (SD = 13.7 years). Patients with severe pain impairment or who were Latinx were more likely to get a newly documented pain diagnosis (absolute risk difference [ARD]: 13.2% and 8.6%, ps < 0.0001), while patients with mental health/substance use or medical comorbidities were less likely (ARDs: −20.0% to −6.2%, ps < 0.001). Factors most consistently associated with treatment were prior treatment of the same modality (4 of 7 treatments, ARDs = 27.3% to 44.1%, ps <0.0001), new pain diagnosis (5 of 7, ARDs = 3.2% to 27.4%, ps <0.001), and severe impairment (4 of 7, ARDs = 2.6% to 6.5%, ps < 0.0001). A new diagnosis had the strongest association with non-opioid pain analgesics and physical medicine (ARD = 27.0% and 27.4%, p < 0.0001). Latinx patients were less likely to receive opioid analgesics and mental health/substance use medications and counseling (ARDs = −3.3% to 7.5%, ps <0.0001).ConclusionScreening and assessment with patient-reported tools may influence pain care. Care for Latinx patients differed from non-Latinx white patients.

Comparison of Analgesic Requirement and Pain Intensity in Lower Segment Cesarean Section (LSCS) with Ketofol and Conventional Induction of General Anesthesia

Objective: to compare the analgesic requirement and pain intensity in LSCS with ketofol and conventional induction of general anesthesia Study Type: randomized controlled trial Study Place and Duration: department of Anesthesiology at Ghazi Medical College &amp; Teaching Hospital, Dera Ghazi Khan, from 1st January 2019 to 30th June 2019. Material and methods: 100 adult participants (20–40 years) ASA physical status 1 and 2, with no previous case of neurologic or cardiovascular undergoing LSCS operations were enlisted in a randomised prospective comparative study after receiving approval from the ethical research committee. Patients were divided into two groups, each with 50 patients: group P (propofol) and group KP (ketamine) (ketofol). The surgeon picked a closed envelope as the method of randomization. Visual analogue scale was used to assess the postoperative pain where, 0 means no pain, 1-3 means mild pain, 4-7 means moderate pain, and 8-10 means severe pain using a visual analog scale, where 0 means no pain, 1-3 means mild pain, 4-7 means moderate pain, and 8-10 means severe pain. Furthermore, the need for postoperative analgesia was examined, including the need for fentanyl. Results: The majority of the patient's Group P and Group KP had 0 VAS scoresof28 (56.0%) and 26 (52.0%), respectively, (p=0.475). Intra operation fentanyl was required 3 (6.0%) in Group P and 1 (2.0%) in Group PK, (p=0.307). While, post-operation fentanyl was required 7 (14.0) in Group P and 4 (8.0) in Group PK, (p=0.338). Conclusion: Ketofol as an induction agent can be used as an alternative which is relatively safe and show less side effects in comparison to propofol alone. Keywords: Ketamine, propofol, ketofol, pain intensity, analgesia requirement, conventional induction, general anesthesia

Sickle cell bone disease and response to intravenous bisphosphonates in children

SummaryChildren with sickle cell disease (SCD) have the potential for extensive and early-onset bone morbidity. This study reports on the diversity of bone morbidity seen in children with SCD followed at three tertiary centers. IV bisphosphonates were effective for bone pain analgesia and did not trigger sickle cell complications.IntroductionTo evaluate bone morbidity and the response to intravenous (IV) bisphosphonate therapy in children with SCD.MethodsWe conducted a retrospective review of patient records from 2003 to 2019 at three Canadian pediatric tertiary care centers. Radiographs, magnetic resonance images, and computed tomography scans were reviewed for the presence of avascular necrosis (AVN), bone infarcts, and myositis. IV bisphosphonates were offered for bone pain management. Bone mineral density was assessed by dual-energy X-ray absorptiometry (DXA).ResultsForty-six children (20 girls, 43%) had bone morbidity at a mean age of 11.8 years (SD 3.9) including AVN of the femoral (17/46, 37%) and humeral (8/46, 17%) heads, H-shaped vertebral body deformities due to endplate infarcts (35/46, 76%), and non-vertebral body skeletal infarcts (15/46, 32%). Five children (5/26, 19%) had myositis overlying areas of AVN or bone infarcts visualized on magnetic resonance imaging. Twenty-three children (8/23 girls) received IV bisphosphonate therapy. They all reported significant or complete resolution of bone pain. There were no reports of sickle cell hemolytic crises, pain crises, or stroke attributed to IV bisphosphonate therapy.ConclusionChildren with SCD have the potential for extensive and early-onset bone morbidity. In this series, IV bisphosphonates were effective for bone pain analgesia and did not trigger sickle cell complications.

Disparities in Prehospital Non-Traumatic Pain Management

Introduction: While prior research has identified racial disparities in prehospital analgesia for traumatic pain, little is known about non-traumatic pain. Using a national prehospital dataset, we sought to evaluate for racial and ethnic disparities in analgesia given by EMS for non-traumatic pain. Methods: We analyzed the 2018 and 2019 data from the ESO Data Collaborative, a collection of de-identified prehospital electronic health records from nearly 1,300 participating EMS agencies in the US. We included all transported, adult, non-traumatic encounters with a primary or secondary impression of a pain complaint, and we stratified encounters based on race and ethnicity as recorded by the EMS clinicians. We performed a mixed model analysis, modeling EMS agency as a random intercept and adjusting for age, sex, pain location, level of service, location of incident, and highest pain score. With non-Hispanic White patients as the reference group, we then evaluated the association between race/ethnicity and receiving any pain medication (acetaminophen, non-steroidal anti-inflammatories, or opioids), receiving opioid pain medication, and receiving pain medication within 20 minutes of EMS arrival. Results: We included 1,035,486 patients; 67.5% non-Hispanic White, 26.8% Black, 4.9% Hispanic, 0.5% Asian, 0.1% Native Hawaiian or Other Pacific Islander, and 0.2% American Indian or Alaska Native patients. 4.7% of patients received pain medications. Compared to White patients (5.1%), Black patients were less likely to receive pain medication (3.3%, aOR 0.7; 95% CI 0.7-0.7) and Hispanics were more likely to receive pain medication (7.6%, aOR 1.5; 95% CI 1.4-1.6). Black patients were also less likely to receive opioids (1.8% for Black v 3.0% for White, aOR 0.7; 95% CI 0.6-0.7), while Hispanic patients were more likely to receive opioids (4.9%, aOR 1.4; 95% CI 1.3-1.5). The odds of receiving pain medication within 20 minutes was lower for Black patients (aOR 0.9; 95% CI 0.8-0.95) but no different for Hispanic patients (aOR 1.0; 95% CI 0.9-1.1), when compared to White patients. Conclusion: Pain medication administration is uncommon for non-traumatic pain complaints. While Black patients were less likely than White patients to receive pain medications and receive pain medication within 20 minutes, Hispanics were more likely to receive pain medications.

Non-opioid analgesics for procedural pain in neonates

Objectives This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To determine the effects of non‐opioid analgesics in neonates (term or preterm) exposed to procedural pain compared to placebo or no drug, non‐pharmacological intervention, other analgesics, or different routes of administration.

Oral Cancer Cells Release Vesicles that Cause Pain.

Oral cancer pain is attributed to the release from cancers of mediators that sensitize and activate sensory neurons. Intraplantar injection of conditioned media (CM) from human tongue cancer cell line HSC-3 or OSC-20 evokes nociceptive behavior. By contrast, CM from noncancer cell lines, DOK, and HaCaT are non-nociceptive. Pain mediators are carried by extracellular vesicles (EVs) released from cancer cells. Depletion of EVs from cancer cell line CM reverses mechanical allodynia and thermal hyperalgesia. CM from non-nociceptive cell lines become nociceptive when reconstituted with HSC-3 EVs. Two miRNAs (hsa-miR-21-5p and hsa-miR-221-3p) are identified that are present in increased abundance in EVs from HSC-3 and OSC-20 CM compared to HaCaT CM. The miRNA target genes suggest potential involvement in oral cancer pain of the toll like receptor 7 (TLR7) and 8 (TLR8) pathways, as well as signaling through interleukin 6 cytokine family signal transducer receptor (gp130, encoded by IL6ST) and colony stimulating factor receptor (G-CSFR, encoded by CSF3R), Janus kinase and signal transducer and activator of transcription 3 (JAK/STAT3). These studies confirm the recent discovery of the role of cancer EVs in pain and add to the repertoire of algesic and analgesic cancer pain mediators and pathways that contribute to oral cancer pain.