Effects of electroacupuncture on pain sensation in a rat model of hyperalgesia with nicotine dependence

Tobacco smoking is considered to be one of the main risk factors in the development of chronic pain.Long-term chronic exposure to nicotine and other forms of tobacco have been shown to be associated with an increased incidence of pain.Studies have shown that acupuncture can help smokers to reduce their desire to smoke,reduce their withdrawal symptoms,and avoid a relapse after treatment.However,little has been reported about the effects of acupuncture on pain sensitivity caused by long-term smoking.Models of hyperalgesia were established in rats exposed to nicotine for 6 weeks.After 6 weeks of continuous nicotine exposure,electroacupuncture at bilateral acupoints Zusanli(ST36)and Taichong(LR3)was performed 20 minutes per day for 6 days at a continuous wave with a frequency of 2 Hz and a stimulus intensity of 1 m A.The results revealed that electroacupuncture treatment increased the mechanical response threshold of hind paw of nicotine-dependent rats with hyperalgesia and up-regulated the protein expression of pain-related factorsμ-opioid receptor,β-endorphin and glutamic acid decarboxylase 65 in the spinal cord and midbrain periaqueductal gray and the protein expression of glutamic acid decarboxylase 67 in the spinal cord.These findings suggest that electroacupuncture treatment has positive analgesic effects on pain sensitivity caused by long-term chronic nicotine exposure.One possible mechanism for the improved analgesia is that electroacupuncture increases the expression of painrelated factors in the spinal cord and midbrain periaqueductal gray.This study was approved by Institutional Animal Care and Use Committee(IACUC)of the University of Miami(#18-167)on December 12,2018.

Mechanism of persistent hyperalgesia in neuropathic pain caused by chronic constriction injury

Transmembrane member 16 A(TMEM16 A) is involved in many physiological functions, such as epithelial secretion, sensory conduction, nociception, control of neuronal excitability, and regulation of smooth muscle contraction, and may be important in peripheral pain transmission. To explore the role of TMEM16 A in the persistent hyperalgesia that results from chronic constriction injury-induced neuropathic pain, a rat model of the condition was established by ligating the left sciatic nerve. A TMEM16 A selective antagonist(10 μg T16 Ainh-A01) was intrathecally injected at L5–6. For measurement of thermal hyperalgesia, the drug was administered once at 14 days and thermal withdrawal latency was recorded with an analgesia meter. For measurement of other indexes, the drug was administered at 12 days,once every 6 hours, totally five times. The measurements were performed at 14 days. Western blot assay was conducted to analyze TMEM16 A expression in the L4–6 dorsal root ganglion. Immunofluorescence staining was used to detect the immunoreactivity of TMEM16 A in the L4–6 dorsal root ganglion on the injured side. Patch clamp was used to detect electrophysiological changes in the neurons in the L4–6 dorsal root ganglion. Our results demonstrated that thermal withdrawal latency was shortened in the model rats compared with control rats.Additionally, TMEM16 A expression and the number of TMEM16 A positive cells in the L4–6 dorsal root ganglion were higher in the model rats, which induced excitation of the neurons in the L4–6 dorsal root ganglion. These findings were inhibited by T16 Ainh-A01 and confirm that TMEM16 A plays a key role in persistent chronic constriction injury-induced hyperalgesia. Thus, inhibiting TMEM16 A might be a novel pharmacological intervention for neuropathic pain. All experimental protocols were approved by the Animal Ethics Committee at the First Affiliated Hospital of Shihezi University School of Medicine, China(approval No. A2017-170-01) on February 27, 2017.

Evidence for Positive Effects of Date Extract That Attenuates Thermal Hyperalgesia in a Diabetic Rat Model of Neuropathic Pain

Aim: Diabetic neuropathic pain is one of the pains which hardly respond to pharmaceutical treat. Today, various chemical and herbal compounds have been used to reduce pain. The aim of this study is to compare the effect of date extract and melatonin in preventing pain in diabetic rats.Method: To study hyperalgesia response and to compare the effect of date extract and melatonin in preventing pain, hot plate and tail flick tests were used. After prescribing single dose of streptozotocin to rats and approving their diabetes, treatment rats received date extract (4ml/kg/day) or melatonin [10 mg/kg/day, intraperitoneally (i.p.)] for a period of 6 weeks. At the end of the sixth week, control and treated rats were examined by thermal pain response and explorative activity tests.Results: According to hot plate results, response time to thermal pain in treated group showed a significant decrease in comparison with the control group (P 0.01). Prescription of date extract increased response time to thermal pain in comparison with treated group (P 0.01), so that response time approximated to control group. Although melatonin approximated to the response time to control group, the significant difference was not observed among melatonin receivers and other groups. In the assessment of diabetic neuropathy on the explorative activity of rats in an open field behavioral test, total distance moved and rearing frequency were significantly decreased, while administration of date extract did also improve motor deficits induced by STZ. Conclusions:Findings of this study showed that date extract decreased thermal hyperalgesia and can prevent pain resulted from diabetic neuropathy.

Guidance on opioids prescribing for the management of persistent non-cancer pain in older adults

Many older adults suffer from persistent pain but prevalence studies consistently showed high levels of untreated or under-treated pain in old population.Both persistent pain and pain under-treatment adversely affect independence and quality of life in geriatric patients.Pain management is challenging in this age-group because of the declining organ function,the presence of concurrent diseases and polypharmacy.For all the above reasons,persistent pain in the elderly should be considered a geriatric syndrome per se and effective approaches are warranted.Current guidelines and consensus statements recommend opioid therapy for older adults with moderateto-severe persistent pain or functional impairment and diminished quality of life due to pain.However clinicians and patients themselves have some concerns about opioids use.Age-related decline in organs functions and warnings about risk of addiction and drug misuse/abuse also in geriatric patients need particular attention for safe prescribing.On the basis of clinical evidence,these practical recommendations will help to improve the competence on opioid role in persistent pain management and the likelihood of a successful analgesic trial in older patients.

Facial pain induces the alteration of transient receptor potential vanilloid receptor 1 expression in rat trigeminal ganglion

Objective To investigate the involvement of transient receptor potential vanilloid receptor 1 （TRPV1） in the facial inflammatory pain in relation to thermal hyperalgesia and cold pain sensation. Methods Facial inflammatory pain model was developed by subcutaneous injection of turpentine oil （TO） into rat facial area. Head withdrawal thermal latency （HWTL） and head withdrawal cold latency （HWCL） were measured once a day for 21 d after TO treatment using thermal and cold measurement apparatus. The immunohistochemical staining, cell-size frequency analysis and the survey of average optical density （OD） value were used to observe the changes of TRPV1 expression in the neurons of the trigeminal ganglion （TG）, peripheral nerve fibers in the vibrissal pad, and central projection processes in the trigeminal sensory nuclei caudalis （Vc） on day 3, 5, 7, 14, and 21 after TO injection. Results HWTL and HWCL decreased significantly from day 1 to day 14 after TO injection with the lowest value on day 5 and day 3, respectively, and both recovered on day 21. The number of TRPV1-labeled neurons increased remarkably from day 1 to day 14 with a peak on day 7, and returned back to the normal level on day 21. In control rats, only small and medium-sized TG neurons were immunoreactive （IR） to TRPV1, and the TRPV1-IR terminals were abundant in both the vibrissal pad and the Vc. Within 2 weeks of inflammation, the expression of TRPV1 in small and medium-sized TG neurons increased obviously. Also the TRPV1 stained terminals and fibers appeared more frequent and denser in both the vibrissal pad skin and throughout laminae Ⅰ and the outer zone of laminae Ⅱ （Ⅱo） of Vc. Conclusion Facial inflammatory pain could induce hyperalgesia to noxious heat and cold stimuli, and result in increase of the numbers of TRPV1 positive TG neurons and the peripheral and central terminals of TG. These results suggest that the phenotypic changes of TRPV1 expression in small and medium-sized TG neurons and terminals might play an important role in the development and maintenance of TO-induced inflammatory thermal hyperalgesia and cold pain sensation.

Adaptive Modeling of Monthly Depression Levels in Terms of Daily Assessments of Opioid Medications Taken and Pain Levels for Cancer Patients

A research study collected intensive longitudinal data from cancer patients on a daily basis as well as non-intensive longitudinal survey data on a monthly basis. Although the daily data need separate analysis, those data can also be utilized to generate predictors of monthly outcomes. Alternatives for generating daily data predictors of monthly outcomes are addressed in this work. Analyses are reported of depression measured by the Patient Health Questionnaire 8 as the monthly survey outcome. Daily measures include numbers of opioid medications taken, numbers of pain flares, least pain levels, and worst pain levels. Predictors are averages of recent non-missing values for each daily measure recorded on or prior to survey dates for depression values. Weights for recent non-missing values are based on days between measurement of a recent value and a survey date. Five alternative averages are considered: averages with unit weights, averages with reciprocal weights, weighted averages with reciprocal weights, averages with exponential weights, and weighted averages with exponential weights. Adaptive regression methods based on likelihood cross-validation (LCV) scores are used to generate fractional polynomial models for possible nonlinear dependence of depression on each average. For all four daily measures, the best LCV score over averages of all types is generated using the average of recent non-missing values with reciprocal weights. Generated models are nonlinear and monotonic. Results indicate that an appropriate choice would be to assume three recent non-missing values and use the average with reciprocal weights of the first three recent non-missing values.

Puerarin ameliorates allodynia and hyperalgesia in rats with peripheral nerve injury

Puerarin is a major active ingredient of the traditional Chinese plant medicine,Radix Puerariae,and commonly used in the treatment of myocardial and cerebral ischemia.However,the effects of puerarin on neuropathic pain are still unclear.In this study,a neuropathic pain animal model was created by partial sciatic nerve ligation.Puerarin（30 or 60 mg/kg） was intraperitoneally injected once a day for 7 days.Mechanical allodynia and thermal hyperalgesia were examined at 1 day after model establishment.Mechanical threshold and paw withdrawal latency markedly increased in a dose-dependent manner in puerarin-treated rats,especially at 7 days after model establishment.At 7 days after model establishment,quantitative real-time reverse transcriptase-polymerase chain reaction results showed that puerarin administration reversed m RNA expression of transient receptor potential vanilloid 1（Trpv1） and transient receptor potential ankyrin 1（Trpa1） in a dose-dependent manner in dorsal root ganglion neurons after peripheral nerve injury.These results suggest that puerarin dose-dependently ameliorates neuropathic pain by suppressing Trpv1 and Trpa1 up-regulation in dorsal root ganglion of neuropathic pain rats.

Na_v1.7 protein and mRNA expression in the dorsal root ganglia of rats with chronic neuropathic pain

Neuropathic pain was produced by chronic constriction injury of the sciatic nerve in rats. Behaviora tests showed that the thresholds for thermal and mechanical hyperalgesia were significantly reduced in neuropathic pain rats 3 28 days following model induction. The results of immunohistochemistry, western blot assays and reverse transcription-PCR showed that Nay1.7 protein and mRNA expression was significantly increased in the injured dorsal root ganglia. These findings indicated that Nay1.7 might play an important role in the model of chronic neuropathic pain

Effects of p38 MAPK inhibitor on the rat pain behavior and proinflammatory cytokines in a metastatic bone cancer pain model

Objective： To observe the effects of p38 mitogen activated protein kinase （MAPK） inhibitor SB203580 by intrathecal injection on the pain behavior and the spinal proinflammatory cytokines in a rat model of bone cancer pain induced by breast cancer cells. Methods： Eleven rats were used to establish the models of bone cancer pain, six rats were treated by intrathecal SB203580 injection, and the other 5 were as the controls. The paw withdrawal latency （PWL）, histology and the spinal levels of IL-1β and TNF-α were detected. Results： All the 11 rats presented evident bone destruction and thermal hyperalgesia after intra-tibial injection of breast cancer cells. No effect of SB203580 on the bone destruction was observed. However, following intrathecal injection of SB203580, the left PWLs （12.12± 1.26 s at 16 days and 12.99 ± 1.65 s at 19 days） were significant higher than that of controls （9.05 ± 1.08 s at 16 days and 8.55 ± 1.60 s at 19 days）, P 〈 0.05. Meanwhile, inkathecal injection of SB203580 evidently reduced the levels of spinal IL-1β and TNF-α. Conclusion： Intrathecal injection of SB203580 in a rat model of bone cancer pain cannot prevent the tibial destruction but significantly depress the thermalgia sensitivity, which might result from inhibiting inkacellular p38 MAPK signaling transduction, and thereby reducing the release of the proinflammatory cytokines.

Effectiveness and safety of acupuncture on cancer pain: a meta-analysis

Objective:The aim of the study was to evaluate the efficacy of acupuncture combined with opiates in the treatment of cancer pain through the meta-analysis system.Methods:China national knowledge infrastructure and VIP Database for Chinese technical periodicals,China Biology Medicine,PubMed,Embase databases were searched from January 2016 to February 8,2020 for the randomized controlled trials on the effects of acupuncture combined with opiates on cancer pain.Meta-analysis of ordered data was performed using Stata-MP64 and Review Manager 5.3 software.Results:A total of 242 Chinese studies and 25 English studies were retrieved.According to the inclusion and exclusion criteria,19 literatures finally were included.The fixed effect model was used to combine the total effect values,and the combined odds ratio(OR)(95%confidence interval(CI))was 2.981(2.384,3.729),suggesting that acupuncture combined with opiates was better than opiates alone in treating cancer pain(Z=9.57,P<0.05);the combination treatment could improve Karnofsky Performance Status score(Z=2.48,P=0.01),decrease Numerical Rating Scale score(Z=2.89,P=0.004);it also could reduce eruption pain frequency(Z=4.32,P<0.0001),improve the effects time(Z=2.51,P=0.01),and extend analgesia duration(Z=4.33,P<0.0001);the combination group also had lower Oxycodone dose than the control group(Z=3.193,P=0.001).At the same time,the incidence of adverse reactions was lower than that of the opiate treatment group alone,with a OR(95%CI)of 0.27(0.19,0.37)and statistical significance,Z=8.06,P<0.05.Conclusion:Acupuncture combined with opioids for cancer pain is superior to opioids alone with a lower incidence of adverse reactions.

Effect of Electro-acupuncture Stimulation of Ximen(PC4) and Neiguan(PC6) on Remifentanil-induced Breakthrough Pain Following Thoracal Esophagectomy

The clinical analgesic effect of electro-acupuncture（EA） stimulation（EAS） on breakthrough pain induced by remifentanil in patients undergoing radical thoracic esophagectomy, and the mechanisms were assessed. Sixty patients（ASAⅢ） scheduled for elective radical esophagectomy were randomized into three groups： group A（control） receiving a general anesthesia only; group B（sham） given EA needles at PC4（Ximen） and PC6（Neiguan） but no stimulation; and group C（EAS） electrically given EAS of the ipsilateral PC4 and PC6 throughout the surgery. The EAS consisting of a disperse-dense wave with a low frequency of 2 Hz and a high frequency of 20 Hz, was performed 30 min prior to induction of general anesthesia and continued through the surgery. At the emergence, sufentanil infusion was given for postoperative analgesia with loading dose of 7.5 μg, followed by a continuous infusion of 2.25 μg/h. The patient self-administration of sufentanil was 0.75 μg with a lockout of 15 min as needed. Additional breakthrough pain was treated with dezocine（5 mg） intravenously at the patient＇s request. Blood samples were collected before（T1）, 2 h（T2）, 24 h（T3）, and 48 h（T4） after operation to measure the plasma β-EP, PGE2, and 5-HT. The operative time, the total dose of sufentanil and the dose of self-administration, and the rescue doses of dezocine were recorded. Visual Analogue Scale（VAS） scores at 2, 12, 24 and 48 h postoperatively and the incidence of apnea and severe hypotension were recorded. The results showed that the gender, age, weight, operative time and remifentanil consumption were comparable among 3 groups. Patients in EAS group had the lowest VAS scores postoperatively among the three groups（P〈0.05）. The total dose of sufentanil was 115±6.0 μg in EAS group, significantly lower than that in control（134.3±5.9 μg） and sham（133.5±7.0 μg） groups. Similarly, the rescue dose of dezocine was the least in EAS group（P〈0.05） among the three groups. Plasma β-EP levels in EAS group at T3（176.90±45.73） and T4（162.96±35.00 pg/mL） were significantly higher than those in control（132.33±36.75 and 128.79±41.24 pg/mL） and sham（136.56±45.80 and 129.85±36.14 pg/mL） groups, P〈0.05 for all. EAS could decrease the release of PGE2. Plasma PGE2 levels in EAS group at T2 and T3（41±5 and 40±5 pg/mL respectively） were significantly lower than those in control（64±5 and 62±7 pg/mL） and sham（66±6 and 62±6 pg/mL） groups. Plasma 5-HT levels in EAS group at T2（133.66±40.85） and T3（154.66±52.49 ng/mL） were significantly lower than those in control（168.33±56.94 and 225.28±82.03） and sham（164.54±47.53 and 217.74±76.45 ng/mL） groups. For intra-group comparison, plasma 5-HT and PGE2 levels in control and sham groups at T2 and T3, and β-EP in EAS group at T3 and T4 were significantly higher than those at T1（P〈0.05）; PGE2 and 5-HT levels in EAS group showed no significant difference among the different time points（P〉0.05）. No apnea or severe hypotension was observed in any group. It was concluded that intraoperative ipsilateral EAS at PC4 and PC6 provides effective postoperative analgesia for patients undergoing radical esophagectomy with remifentanil anesthesia and significantly decrease requirement for parental narcotics. The underlying mechanism may be related to stimulation of the release of endogenous β-EP and inhibition of inflammatory mediators（5-HT and PGE2）.

Multimodal pain stimulation of the gastrointestinal tract

Understanding and characterization of pain and other sensory symptoms are among the most important issues in the diagnosis and assessment of patient with gastrointestinal disorders. Methods to evoke and assess experimental pain have recently developed into a new area with the possibility for multimodal stimulation （e.g., electrical, mechanical, thermal and chemical stimulation） of different nerves and pain pathways in the human gut. Such methods mimic to a high degree the pain experienced in the clinic. Multimodal pain methods have increased our basic understanding of different peripheral receptors in the gut in health and disease. Together with advanced muscle analysis, the methods have increased our understanding of receptors sensitive to mechanical, chemical and temperature stimuli in diseases, such as systemic sclerosis and diabetes. The methods can also be used to unravel central pain mechanisms, such as those involved in allodynia, hyperalgesia and referred pain. Abnormalities in central pain mechanisms are often seen in patients with chronic gut pain and hence methods relying on multimodal pain stimulation may help to understand the symptoms in these patients. Sex differences have been observed in several diseases of the gut, and differences in central pain processing between males and females have been hypothesized using multimodal pain stimulations. Finally, multimodal methods have recently been used to gain more insight into the effect of drugs against pain in the GI tract. Hence, the multimodal methods undoubtedly represents a major step forward in the future characterization and treatment of patients with various diseases of the gut.

Antinociceptive effects of novel melatonin receptor agonists in mouse models of abdominal pain

AIM: To characterize the antinociceptive action of the novel melatonin receptor (MT) agonists, Neu-P11 and Neu-P12 in animal models of visceral pain. METHODS: Visceral pain was induced by intracolonic (ic) application of mustard oil or capsaicin solution or by intraperitoneal (ip) administration of acetic acid. Neu-P11, Neu-P12, or melatonin were given ip or orally and their effects on pain-induced behavioral responses were evaluated. To identify the receptors involved, the non-selective MT1/MT2 receptor antagonist luzindole, the MT2 receptor antagonist 4-P-PDOT, or the mu-opioid receptor antagonist naloxone were injected ip or intra-cerebroventricularly (icv) prior to the induction of pain. RESULTS: Orally and ip administered melatonin, Neu-P11, and Neu-P12 reduced pain responses in a dose-dependent manner. Neu-P12 was more effective and displayed longer duration of action compared to melatonin. The antinociceptive effects of Neu-P11 or Neu-P12 were antagonized by ip or icv. administered naloxone. Intracerebroventricularly, but not ip administration of luzindole or 4-P-PDOT blocked the antinociceptive actions of Neu-P11 or Neu-P12. CONCLUSION: Neu-P12 produced the most potent and long-lasting antinociceptive effect. Further development of Neu-P12 for future treatment of abdominal pain seems promising. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

Chronic pain, posttraumatic stress disorder, and opioid intake: A systematic review

BACKGROUND The literature suggests that there is a high degree of co-occurrence between chronic pain and posttraumatic stress disorder(PTSD). An association has been found between PTSD and substance abuse. PTSD is a severe disorder that should be taken into account when opioids are prescribed. It has been found that the prevalence of opioid use disorder(OUD) in chronic pain patients is higher among those with PTSD than those without this disorder.AIM To perform a systematic review on the association between PTSD, chronic noncancer pain(CNCP), and opioid intake(i.e., prescription, misuse, and abuse).METHODS We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Patient, Intervention,Comparator, and Outcomes(PICOS) criteria were formulated a priori in the protocol of the systematic review. A search was conducted of the PROSPERO database. In March 2019, searches were also conducted of 5 other databases:Pub Med, MEDLINE, Psyc INFO, Web of Science, and PILOTS. The Scottish Intercollegiate Guidelines Network checklist for cohort studies was used to assess the selected studies for their methodological quality and risk of bias. Each study was evaluated according to its internal validity, participant sampling,confounding variables, and the statistical analysis.RESULTS A total of 151 potentially eligible studies were identified of which 17 were retained for analysis. Only 10 met the selection criteria. All the studies were published between 2008 and 2018 and were conducted in the United States. The eligible studies included a total of 1622785 unique participants. Of these, 196516 had comorbid CNCP and PTSD and were consuming opiates. The participants had a cross-study mean age of 35.2 years. The majority of participants were men(81.6%). The most common chronic pain condition was musculoskeletal pain:back pain(47.14% across studies;range: 16%-60.6%), arthritis and joint pain(31.1%;range: 18%-67.5%), and neck pain(28.7%;range: 3.6%-63%). In total,42.4% of the participants across studies had a diagnosis of PTSD(range: 4.7%-95%). In relation to opioid intake, we identified 2 different outcomes: opioid prescription and OUD. All the studies reported evidence of a greater prevalence of PTSD in CNCP patients who were receiving prescribed opioids and that PTSD was associated with OUD in CNCP patients.CONCLUSION Opioid analgesic prescription as the treatment of choice for CNCP patients should include screening for baseline PTSD to ensure that these drugs are safely consumed.

Trends and risk factors for opioid administration for non-emergent lower back pain

BACKGROUND Non-emergent low-back pain(LBP)is one of the most prevalent presenting complaints to the emergency department(ED)and has been shown to contribute to overcrowding in the ED as well as diverting attention away from more serious complaints.There has been an increasing focus in current literature regarding ED admission and opioid prescriptions for general complaints of pain,however,there is limited data concerning the trends over the last decade in ED admissions for non-emergent LBP as well as any subsequent opioid prescriptions by the ED for this complaint.AIM To determine trends in non-emergent ED visits for back pain;annual trends in opioid administration for patients presenting to the ED for back pain;and factors associated with receiving an opioid-based medication for non-emergent LBP in the ED METHODS Patients presenting to the ED for non-emergent LBP from 2010 to 2017 were retrospectively identified from the National Hospital Ambulatory Medical Care Survey database.The“year”variable was transformed to two-year intervals,and a weighted survey analysis was conducted utilizing the weighted variables to generate incidence estimates.Bivariate statistics were used to assess differences in count data,and logistic regression was performed to identify factors associated with patients being discharged from the ED with narcotics.Statistical significance was set to a P value of 0.05.RESULTS Out of a total of 41658475 total ED visits,3.8%(7726)met our inclusion and exclusion criteria.There was a decrease in the rates of non-emergent back pain to the ED from 4.05%of all cases during 2010 and 2011 to 3.56%during 2016 and 2017.The most common opioids prescribed over the period included hydrocodone-based medications(49.1%)and tramadol-based medications(16.9),with the combination of all other opioid types contributing to 35.7%of total opioids prescribed.Factors significantly associated with being prescribed narcotics included age over 43.84-years-old,higher income,private insurance,the obtainment of radiographic imaging in the ED,and region of the United States(all,P<0.05).Emergency departments located in the Midwest[odds ratio(OR):2.42,P<0.001],South(OR:2.35,<0.001),and West(OR:2.57,P<0.001)were more likely to prescribe opioid-based medications for non-emergent LBP compared to EDs in the Northeast.CONCLUSION From 2010 to 2017,there was a significant decrease in the number of nonemergent LBP ED visits,as well as a decrease in opioids prescribed at these visits.These findings may be attributed to the increased focus and regulatory guidelines on opioid prescription practices at both the federal and state levels.Since nonemergent LBP is still a highly common ED presentation,conclusions drawn from opioid prescription practices within this cohort is necessary for limiting unnecessary ED opioid prescriptions.

Review of Coeliac Plexus Blockade for the Management of Chronic Pancreatitis Pain at Tallaght University Hospital (TUH)

Background: Pain is a major problem for patients suffering from chronic pancreatitis. Unfortunately, medical therapy often fails to adequately control pain. Coeliac plexus block (CPB) is sometimes performed to treat intractable pain in patients with chronic pancreatitis. Aims: Our primary objective was to determine the effect of CPB for pain management in a cohort of patients with chronic pancreatitis. We also sought to quantify opioid use in patients with chronic pancreatitis. Methods: We reviewed the database of pain referrals for chronic pancreatitis and recorded opioid use for each patient. We interviewed all patients who underwent CPB for chronic pancreatitis at TUH from January 2018-December 2020. Effect of the block, duration of pain relief, analgesia requirements, complications and patient satisfaction were recorded. Results: 62 inpatient referrals were made to the pain service over a 3-year period regarding pain management in chronic pancreatitis. 76% of patients referred for chronic pancreatitis pain management require regular long-term opioids. Mean daily oxycodone requirement in this group was 52 mg. 11 of these patients underwent CPB over a 3-year period. Mean age of patients who underwent CPB was 44 years. Effective reduction in pain scores (>50% improvement) was achieved in 7 of 11 patients. The mean NRS pain score decreased from 9.2 (±0.9) to 4.4 (±3.1). Mean duration of pain relief experienced was 69 days. Transient diarrhoea was reported by 1 patient. 4 patients reported a temporary decrease in oral analgesia requirement, while 3 patients reported a sustained decrease in analgesia requirement post CPB. For those who had further CPBs, the effect of repeated interventions was comparable to the initial procedure. Conclusion: High regular opioid consumption is common in patients with chronic pancreatitis. CPB can provide significant improvement in pain control and quality of life in appropriately selected patients. CPB can assist with opioid reduction and containment. It is not effective in all cases and there is high inter-patient variability. The procedure has a good safety profile.

Newborn with Giant Non-Involuting Congenital Hemangioma: Mechanisms of Allodynia, Hyperalgesia and Treatment

In a newborn affected by a non involuting congenital hemangioma we measured allodynia through the application of a standard tactile stimulus and hyperalgesia through the regular administration of the Comfort scale which rates pain intensity. The baby presented signs of these pathological events over long periods of the disease. They may be attributed to the high amount of the nociceptive ligands in the hemangioma microenviroment and to the elevated concentration of TNF-alpha and IL-6 in the blood. For a long time, the pain was relieved by a combination of opioids, adjuvants and paracetamol, but also by thalidomide and unexpectedly by interferon alpha. A mechanism-based pain treatment needs to take into account the processes underlying pain and also the ongoing pathology.

Salient concerns in using analgesia for cancer pain among outpatients: A cluster analysis study

AIM To identify unique clusters of patients based on their concerns in using analgesia for cancer pain and predictors of the cluster membership.METHODS This was a 3-mo prospective observational study(n = 207).Patients were included if they were adults(≥ 18 years), diagnosed with solid tumors or multiple myelomas, and had at least one prescription of around the clock pain medication for cancer or cancer-treatment-related pain.Patients were recruited from two outpatient medical oncology clinics within a large health system in Philadelphia.A choice-based conjoint(CBC) analysis experiment was used to elicit analgesic treatment preferences(utilities).Patients employed trade-offs based on five analgesic attributes(percent relief from analgesics, type of analgesic, type of sideeffects, severity of side-effects, out of pocket cost).Patients were clustered based on CBC utilities using novel adaptive statistical methods.Multiple logistic regression was used to identify predictors of cluster membership.RESULTS The analyses found 4 unique clusters: Most patients made trade-offs based on the expectation of pain relief(cluster 1, 41%).For a subset, the main underlying concern was type of analgesic prescribed, i.e., opioid vs non-opioid(cluster 2, 11%) and type of analgesic side effects(cluster 4, 21%), respectively.About one in four made trade-offs based on multiple concerns simultaneously including pain relief, type of side effects, and severity of side effects(cluster 3, 27.5%).In multivariable analysis, to identify predictors of cluster membership, clinical and socioeconomic factors(education, health literacy, income, social support) rather than analgesic attitudes and beliefs were found important; only the belief, i.e., pain medications can mask changes in health or keep you from knowing what is going on in your body was found significant in predicting two of the four clusters [cluster 1(-); cluster 4(+)].CONCLUSION Most patients appear to be driven by a single salient concern in using analgesia for cancer pain.Addressing these concerns, perhaps through real time clinical assessments, may improve patients' analgesic adherence patterns and cancer pain outcomes.

Fluctuation of visual analog scale pain scores and opioid consumption before and after total hip arthroplasty

BACKGROUND Patients who undergo orthopedic procedures are often given excess opioid medication.Understanding the relationship between pain and opioid consumption following total hip arthroplasty(THA)is key to creating safe and effective opioid prescribing guidelines.AIM To evaluate the association between the quantity of opioid consumption in relation to pain scores both pre-and postoperatively in patients undergoing primary THA.METHODS We retrospectively reviewed patients who underwent primary THA from November 2018-May 2019 and answered both the visual analog scale(VAS)pain and opioid medication questionnaires pre-and postoperatively.Both surveys were delivered daily for 7-days before surgery through the first 30 postoperative days.Survey results were divided into preoperative,postoperative days 1-7,postoperative days 8-14,and postoperative days 15-30 for analysis.Mean opioid pill consumption and VAS pain scores in each time period were determined and compared to patients’preoperative status using hierarchical Poisson and linear regressions,respectively.RESULTS There were 105 patients included.Mean VAS pain scores were the highest preoperatively 7.41±1.72.However,VAS pain scores significantly declined in each successive postoperative category compared to preoperative scores:postoperative day 1-7(5.07±1.79;P<0.001),postoperative day 8-14(3.60±1.64;P<0.001),and postoperative day 15-30(3.15±1.63;P<0.001).Mean opioid pill consumption preoperatively was 0.68±1.29 pills.Compared to preoperative opioid consumption,opioid use was significantly greater between postoperative days 1-7(1.51±1.58;P=0.001)and postoperative days 8-14(1.00±1.27;P=0.043).Opioid consumption declined below preoperative levels between postoperative days 15-30(0.35±0.72;P=0.160)which correlates with a VAS pain score of 3.15.CONCLUSION All patients experienced significant benefit and pain relief from having undergone THA.Average postoperative opioid consumption decreased below preoperative consumption between postoperative days 15-30,which was associated with a VAS pain score of 3.15.These results can be used to appropriately guide opioid prescribing practices and set patient expectations regarding pain management following THA.

Comparison between intravenous morphine versus fentanyl in acute pain relief in drug abusers with acute limb traumatic injury

BACKGROUND: Rapid and effective pain relief in acute traumatic limb injuries(ATLI) is one of the most important roles of emergency physicians. In these situations, opioid addiction is an important concern because of the dependency on opioids. The study aims to compare the effectiveness of intravenous(IV) fentanyl versus morphine in reducing pain in patients with opioid addiction who suffered from ATLI.METHODS: In this double-blind randomized clinical trial, 320 patients with ATLI, who presented to the emergency department(ED) from February 2016 to April 2016, were randomly divided into two groups. One group(160 patients) received 0.1 mg/kg IV morphine. The other group(160 patients) received 1 mcg/kg IV fentanyl. Patients' demographic data, pain score at specif ic intervals, vital signs, side effects, satisfaction and the need for rescue analgesia were recorded.RESULTS: Eight patients in the morphine group and five patients in the fentanyl group were excluded. Pain score in the fentanyl group had a significant decrease at 5-minute follow-up(P value=0.00). However, at 10, 30, and 60-minute follow-ups no signifi cant differences were observed between the two groups in terms of pain score reduction. The rescue analgesia was required in 12(7.7%) patients in the fentanyl group and in 48(31.6%) patients in the morphine group(P value=0.00). No signifi cant difference was observed regarding side effects, vital signs and patients' satisfaction between the two groups.CONCLUSION: Fentanyl might be an effective and safe drug in opioid addicts suffering from ATLI.