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Objective: Qualitative assessment investigating patients’ perceptions related to opioids including their role in pain control, risks, and handling and disposal prior to undergoing hip replacement.Design: A prospective, cross-sectional survey study.Setting: Large urban teaching hospital specializing in orthopedic surgery affiliated with Weill Cornell Medical College.Participants: Patients aged 18-80, English-speaking, without recent or chronic opioid use, and planning to undergo primary total hip replacement. A total of 128 patients were enrolled and completed the study.Intervention: A 27-item interview evaluating perceptions on opioid-related topics.Main outcome measures: Responses to interview questions were documented by research assistant.Results: Most patients believe that there should be minimal or no pain with the use of opioids, though they also agree that opioids should be limited to pain that interferes with function or activity. Patients generally appreciate risks of addiction with opioids but are less familiar with risks associated with sleep apnea and sedatives. Minority of patients understand that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in combination with opioids would effectively reduce pain. Majority of patients were unsure of how to properly store and dispose of opioids.Conclusions: Qualitative assessment demonstrates that patients may benefit from education and discussion specifically about pain expectations, the role of opioids in treating pain, multimodal analgesia, and proper storage and disposal.

Background Opioids are the most commonly prescribed analgesics in the United States. Current guidelines have proposed education initiatives to reduce the risk of chronic opioid consumption, yet there is lack of efficacy data on such interventions. Our study evaluates the impact of perioperative opioid education on postoperative opioid consumption patterns including opioid cessation, number of pills consumed, and opioid prescription refills. Methods The MEDLINE/PubMed, Embase, Cochrane Library, Scopus, and Google Scholar databases were systematically searched for randomized controlled trials (RCTs) assessing the impact of perioperative educational interventions (using either paper- or video-based instruments regarding pain management and drug-induced side effects) on postoperative opioid patterns compared to standard preoperative care among patients undergoing elective surgery. Our end points were opioid consumption (number of pills used), appropriate disposal of unused opioids, opioid cessation (defined as no use of opioids), and opioid refills within 15 days, 6 weeks, and 3 months. Results In total, 11 RCTs fulfilled the inclusion criteria, totaling 1604 patients (804 received opioid education, while 800 received standard care). Six trials followed patients for 15 days after surgery, and 5 trials followed patients up to 3 months. After 15 days, the opioid education group consumed a lower number of opioid pills than those in the control group (weighted mean difference [WMD], -3.39 pills; 95% confidence interval [CI], -6.40 to -0.37; P =.03; I2 = 69%) with no significant difference in overall opioid cessation (odds ratio [OR], 0.25; 95% CI, 0.04-1.56; P = .14; I2 = 83%). Likewise, perioperative opioid education did not have significant effects on opioid cessation at 6 weeks (OR, 0.69; 95% CI, 0.45-1.05; P = .10; I2 = 0%) and 3 months (OR, 0.59; 95% CI,0.17-2.01; P = .10; I2 = 0%) after surgery, neither reduced the need for opioid refills at 15 days (OR, 0.57; 95% CI, 0.28-1.15; P = .12; I2 = 20%) and 6 weeks (OR, 1.08; 95% CI, 0.59-1.98; P = .80; I2 = 37%). There was no statistically significant difference in the rate of appropriate disposal of unused opioids between both groups (OR, 1.99; 95% CI, 0.66-6.00; P = .22; I2 = 71%). Subgroup analysis by type of educational intervention showed a statistical reduction of opioid consumption at 15 days when implementing multimedia/audiovisual strategies (4 trials: WMD, -4.05 pills; 95% CI, -6.59 to -1.50; P = .002; I2 = 45%), but there was no apparent decrease when using only paper-based strategies (2 trials: WMD, -2.31 pills; 95% CI, -12.21 to 7.59; P = .65; I2 = 80%). Conclusions Perioperative educational interventions reduced the number of opioid pills consumed at 15 days but did not demonstrate a significant effect on opioid cessation or opioid refills at 15 days, 6 weeks, and 3 months. Further randomized trials should focus on evidence-based educational interventions with strict homogeneity of material to draw a more definitive recommendation.

Cannabis use is increasingly common, and with a growing number of jurisdictions implementing legalization frameworks, it is likely that providers will encounter more patients who use cannabis. Therefore, it is important for providers to understand the implications of cannabis use and practical considerations for the perioperative period. Cannabis affects multiple organ systems and may influence intraoperative anesthesia, as well as postoperative pain management. The effects of cannabis and key anesthetic considerations are reviewed here.

Objectives Spinal cord ischemia secondary to trauma or a vascular occlusive event is a threatening phenomenon. The neuroprotective properties of minocycline have been shown in several models of central nervous system diseases and after spinal cord ischemia; however, the benefit of using the drug requires additional confirmation in different animal models. Astrocytes are essential as regulators of neuronal functions and for providing nutrients. The authors hypothesized that astrocytes in the spinal cord may be an important target for minocycline action after ischemia and thus in the prevention of secondary spreading damage. Design A prospective, randomized animal study. Setting University research laboratory, single institution. Participants Adult male Sprague Dawley rats, weighing between 400 and 450 g. Interventions A model of spinal cord ischemia in the rat was used for this study to determine whether a single, high-dose (10 mg/kg) of minocycline protects against damage to the neuronal cytoskeleton, both in the white and gray matter, and whether it reduces glial fibrillary acidic protein levels, which is an index for prevention of astrocyte activation during ischemia. Thirty minutes before thoracic aorta occlusion, minocycline was administered for 18 minutes using a 2 F Fogarty catheter. Measurements and Main Results Minocycline given prophylactically significantly mitigated severe hindlimb motor impairment and reduced glial fibrillary acidic protein plus astrocytosis in both the white and gray matter of the spinal cord, caudal to the occlusion. Neuronal histologic cytoarchitecture, which was severely and significantly compromised in control animals, was preserved in the minocycline-treated animals. Conclusions This study's data imply that minocycline may attenuate reactive astrocytosis in response to injury with better neurologic outcome in a model of spinal cord ischemia in rats. The data suggest that future use of minocycline, clinically, might be advantageous in surgeries with a potential risk for paraplegia due to spinal cord ischemia.

BackgroundThere is growing evidence that cytokines and adipokines are associated with osteoarthritis (OA) severity, progression, and severity of associated pain. However, the cytokine response to total knee arthroplasty (TKA) and its association with persistent postoperative pain is not well understood. This study aims to describe the perioperative systemic (plasma) and local (synovial fluid) cytokine profiles of patients who do and do not develop persistent pain after TKA.MethodsPatients undergoing primary unilateral TKA for end-stage OA were prospectively enrolled. Demographic and clinical data were gathered preoperatively and postoperatively. Synovial fluid was collected pre arthrotomy and plasma was collected at multiple time points before and after surgery. Persistent postoperative pain (PPP) was defined as Numerical Rating Score≥4 at 6 months. Cytokine levels were measured using the V-Plex Human Cytokine 30-Plex Panel (Mesoscale—Rockville, Maryland, USA). Cytokine levels were compared between PPP and minimal pain groups. Given that the study outcomes are exploratory, no adjustment was performed for multiple testing.ResultsIncidence of persistent pain at 6 months post TKA was 15/162 (9.3%). Postoperative plasma levels of four cytokines were significantly different in patients who developed persistent postoperative pain: interleukin (IL)-10, IL-1β, vascular endothelial growth factor, and IL12/IL23p40. Significantly lower IL-10 levels in the prearthrotomy synovial fluid were associated with development of postoperative persistent pain.ConclusionsThis prospective cohort study described a distinct acute perioperative inflammatory response profile in patients who developed persistent post-TKA pain, characterized by significant differences in four cytokines over the first 2 postoperative days. These results support the growing evidence that the patient-specific biologic response to surgery may influence longer-term clinical outcomes after TKA.Trial registration numberClinicaltrials.gov NCT02626533.

BACKGROUND Spinal anesthesia is known to have numerous benefits, including reductions in nausea and opioid consumption; however, postdural puncture headache (PDPH) remains a significant risk associated with this technique. The literature specifically examining this complication in adolescents is scarce. Our primary objective was therefore (1) to estimate the incidence of PDPH with a 27G pencil-point needle in patients between the ages of 12 and 19 undergoing ambulatory lower extremity procedures and (2) to compare it to the incidence in adults aged 20-45 years. METHODS After institutional review board (IRB) approval, patients aged 12-45 years undergoing ambulatory lower extremity surgery were approached. Patients undergoing the procedure under combined spinal-epidural (CSE) or spinal anesthesia with a 27G pencil-point needle were eligible for enrollment. Patients were consented before surgery and received a survey via e-mail on postoperative day (POD) 4 inquiring about the presence of a headache. Each headache was described by the participant and assessed for severity, time of onset, duration, location, and whether it was of a postural nature. All patients reporting a postural headache were contacted by a physician author to confirm a diagnosis of PDPH using the International Headache Society diagnostic criteria. RESULTS A total of 656 patients were included in the analysis. Overall, 3.4% of patients developed PDPH. The percentage developing PDPH was 4.9% (3.0-7.8) among those aged 12-19 years and 1.8% (0.8-3.9) in the 20- to 45-year-old group. After adjusting for covariates, the age group between 12 and 19 years was associated with an almost 3-fold increase in the odds (2.8 [95% confidence interval {CI}, 1.1-7.3]) for the development of PDPH compared to that in the 20-45 age group. One patient in the adult group required an epidural blood patch. CONCLUSIONS The overall incidence for the development of PDPH in ambulatory patients

Background AMPAkines augment the function of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the brain to increase excitatory outputs. These drugs are known to relieve persistent pain. However, their role in acute pain is unknown. Furthermore, a specific molecular and anatomic target for these novel analgesics remains elusive. Methods The authors studied the analgesic role of an AMPAkine, CX546, in a rat paw incision (PI) model of acute postoperative pain. The authors measured the effect of AMPAkines on sensory and depressive symptoms of pain using mechanical hypersensitivity and forced swim tests. The authors asked whether AMPA receptors in the nucleus accumbens (NAc), a key node in the brain’s reward and pain circuitry, can be a target for AMPAkine analgesia. Results Systemic administration of CX546 (n = 13), compared with control (n = 13), reduced mechanical hypersensitivity (50% withdrawal threshold of 6.05 ± 1.30 g [mean ± SEM] vs. 0.62 ± 0.13 g), and it reduced depressive features of pain by decreasing immobility on the forced swim test in PI-treated rats (89.0 ± 15.5 vs. 156.7 ± 18.5 s). Meanwhile, CX546 delivered locally into the NAc provided pain-relieving effects in both PI (50% withdrawal threshold of 6.81 ± 1.91 vs. 0.50 ± 0.03 g; control, n = 6; CX546, n = 8) and persistent postoperative pain (spared nerve injury) models (50% withdrawal threshold of 3.85 ± 1.23 vs. 0.45 ± 0.00 g; control, n = 7; CX546, n = 11). Blocking AMPA receptors in the NAc with 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione inhibited these pain-relieving effects (50% withdrawal threshold of 7.18 ± 1.52 vs. 1.59 ± 0.66 g; n = 8 for PI groups; 10.70 ± 3.45 vs. 1.39 ± 0.88 g; n = 4 for spared nerve injury groups). Conclusions AMPAkines relieve postoperative pain by acting through AMPA receptors in the NAc.

Background The function of the Cannabinoid 1 receptor (CB1R) in the development of neuropathic pain is not clear. Mounting evidence suggest that CB1R expression and activation may contribute to pain. Cannabinoid 1 receptor knockout mice (CB1R−/−) generated on a C57Bl/6 background exhibit hypoalgesia in the hotplate assay and formalin test. These findings suggest that Cannabinoid 1 receptor expression mediates the responses to at least some types of painful stimuli. By using this mouse line, we sought to determine if the lack of Cannabinoid 1 receptor unveils a general hypoalgesic phenotype, including protection against the development of neuropathic pain. The acetone test was used to measure cold sensitivity, the electronic von Frey was used to measure mechanical thresholds before and after spared-nerve injury, and analysis of footprint patterns was conducted to determine if motor function is differentially affected after nerve-injury in mice with varying levels of Cannabinoid 1 receptor. Results At baseline, CB1R−/− mice were hypersensitive in the acetone test, and this phenotype was maintained after spared-nerve injury. Using calcium imaging of lumbar dorsal root ganglion (DRG) cultures, a higher percentage of neurons isolated from CB1R−/− mice were menthol sensitive relative to DRG isolated from wild-type (CB1R+/+) mice. Baseline mechanical thresholds did not differ among genotypes, and mechanical hypersensitivity developed similarly in the first two weeks following spared-nerve injury (SNI). At two weeks post-SNI, CB1R−/− mice recovered significantly from mechanical hypersensitivity, while the CB1R+/+ mice did not. Heterozygous knockouts (CB1R+/−) transiently developed cold allodynia only after injury, but recovered mechanical thresholds to a similar extent as the CB1R−/− mice. Sciatic functional indices, which reflect overall nerve health, and alternation coefficients, which indicate uniformity of strides, were not significantly different among genotypes. Conclusion Cold allodynia and significant recovery from spared-nerve injury-induced mechanical hypersensitivity are two novel phenotypes which characterize the global CB1R−/− mice. An increase in transient receptor potential channel of melastatin 8 channel function in DRG neurons may underlie the cold phenotype. Recovery of mechanical thresholds in the CB1R knockouts was independent of motor function. These results indicate that CB1R expression contributes to the development of persistent mechanical hypersensitivity, protects against the development of robust cold allodynia but is not involved in motor impairment following spared-nerve injury in mice.