UWMC Department of Anesthesiology and Pain Medicine

PRE-OPERATIVE METHODS: QUESTIONNAIRES, mTS &amp; DNIC
Part 1: Demographic, Psychosocial &amp; Pain-related Personality Questionnaires
<ol>
 <li>First, a demographic questionnaire is administered to collect data related to women s medical history, including pain preceding pregnancy and recent history during pregnancy and up to their delivery. </li>
 <li>Psychosocial questionnaires are administered before the DNIC procedure and during two 5-minute breaks that fall within the DNIC procedure. The Spielberger's State-Trait Anxiety Inventory is administered before the procedure, the Fear of Pain Questionnaire-III is administered during the first 5-minute break and the Pain Catastrophizing Scale questionnaire is administered during the second 5-minute break. The Spielberger's State-Trait Anxiety Inventory states emotional conditions and assesses first the level of state anxiety and then assesses the level of trait anxiety. The Fear of Pain Questionnaire-III contains descriptions of severe pain, minor pain, and medical pain. The Pain Catastrophizing Scale includes items that represent the three components of pain catastrophizing: rumination, magnification, and helplessness. </li>
 <li>Lastly, the Short-Form McGill Pain Questionnaire 2 may be administered at any convenient time point pre-operatively to quantify the degree of neuropathic and non-neuropathic pain a subject experiences.</li>
 </ol>
Part 2: Mechanical Temporal Summation (mTS) Assessment
<ol>
 <li>On the woman s forearm, the researcher applies a 180 gram von Frey filament once or twice to familiarize with the pinprick sensation. Then it is applied 11 times within a 1 cm diameter circle. After one touch, the woman is asked to rate the pinprick pain on a 0-100 verbal numerical pain scale. Then ten consecutive touches are applied at random locations with a 1 second interstimulus interval and the subject is asked to rate the pain of the 10th application.</li>
</ol>
Part 3: Diffuse Noxious Inhibitory Control (DNIC) Assessment
<ol>
 <li>In a private exam room, the pregnant woman is seated in a comfortable position with a pillow placed in her lap. Women are told that small-talk and conversation will not take place during the test in order to obtain consistent results. Women are asked to concentrate as best they can on the instructions that are described to them. The researcher follows a script to administer instructions. First, the 11-point verbal numerical pain scale is explained and then the test is briefly explained.</li>
 <li>The heat thermode is carefully placed on the inside part of the woman's dominant volar forearm and is secured with a Velcro strap. The woman is asked to relax her arm while keeping the thermode in the same position.</li>
 <li>The first part of the test involves familiarizing the woman with two distinct heat sensations and getting her used to rating the painful sensation upon request. The thermode increases and decreases at 8&deg;C/sec from 32&deg;C to 43&deg;C and then again from 32&deg;C to 44&deg;C. Each target temperature, first 43&deg;C and 44&deg;C, remains for 7 seconds. The interstimulus interval is set to 2 seconds. The increasing/decreasing rate and interstimulus interval settings remain at 8&deg;C/sec and 2 seconds, respectively, throughout the entire procedure. When not activated, the thermode rests at a baseline temperature of 32&deg;C. The subject is asked to rate the pain on an 11-point verbal numerical pain scale six seconds after the thermode reaches the target temperature.</li>
 <li>The next part of the test involves applying three consecutive temperatures to determine the temperature the woman reports with a pain intensity of 6 on the 0-10 scale. This is done by first heating the thermode to 45, 46 and 47&#730;C in random order. Depending on the responses of the woman for each temperature, the range of the three temperatures will be increased or decreased by 1&#730;C. The thermode is not able to reach temperatures above 48&#730;C. </li>
 <li>The pain-6 temperature is then confirmed.</li>
 <li>Now the thermode is removed from the woman s forearm for at least 5 minutes. This is a good time for a subject to complete questionnaires and paperwork.</li>
 <li>After at least 5 minutes, the thermode is placed in the same position on the woman s forearm. </li>
 <li>The next part of the test involves the thermode heating up to the pain-6 temperature for 30 seconds. The woman is asked to rate the pain at 0, 10, 20, and 30 seconds during the test stimulus. This 30 second heat stimulus is the first test stimulus. </li>
 <li>Again, the thermode is removed from the woman s forearm for at least 5 minutes, during which time more questionnaires and paperwork may be completed.</li>
 <li>After at least 5 minutes, the thermode is placed once again in the same position on the woman s forearm.</li>
 <li>For the last part of the test, the DNIC pathway will be tested with the hot water bath conditioning stimulus. The water in the water bath is kept at a constant 46.5&#730;C. The woman submerges her entire hand (the non-dominant one) until the wrist in the water for a full minute and during the last 30 seconds of the minute the thermode heats up to the same pain-6 temperature. For the first 30 seconds, the woman is asked to rate every 10 seconds the painful sensation generated by the hand in the water bath. Then, for the last 30 seconds, she is asked to rate the painful sensation caused by the thermode (at 40, 50 and 60 seconds time points).</li>
 </ol>
Part 4: Calculation of DNIC and mTS
<ol>
 <li>Mechanical temporal summation is calculated by subtracting the pain rating after the 1st touch from the pain rating after the 10th touch.</li>
 <li>To calculate a DNIC score, the average of the last three pain ratings or the last pain rating of the unconditioned test stimulus is subtracted from the average of the last three pain ratings or the last pain rating of the conditioned test stimulus, respectively.</li>
 </ol>
PERI-PARTUM DATA
Part 5: Delivery Information
Mode of delivery, analgesia for labor and delivery or standardized spinal anesthesia for cesarean section and obstetrical and neonatal demographics are recorded.
Part 6: Clinical Pain Ratings and Pain Medication
Pain ratings on an 11-point numerical pain scale are collected during the time of labor and delivery and 12, 24 and 48 hours post-operatively. For women with a scheduled cesarean section, pain ratings are recorded at the time of the incision, the delivery of the baby, and the time skin staples or sutures are placed. Post-operatively, pain ratings around the incision are recorded while resting, sitting and in general from her uterus cramping.
The time points and doses of any opioids, acetaminophen, and non-steroidal anti-inflammatory drugs consumed 0 to 48 hours postpartum for post-operative pain are documented. Information regarding the duration of the epidural effect is recorded.
Part 7: Blood sample
Peripheral blood is obtained (EDTA vacutainer, 3ml) for DNA extraction.
POST-CESAREAN DELIVERY
Part 8: 48-hour Wound Hyperalgesia
<ol>
 <li>Dynamic and static hyperalgesia are assessed 48 hours after cesarean delivery.</li>
 <li>First, the area of dynamic hyperalgesia for punctate mechanical stimuli around the surgical incision is measured around the scar according to the method described by Stubhaug et al. (1997). In brief, stimulation with a 180 gram von Frey Filament is started from outside the hyperalgesic area where no pain sensation is experienced and moved toward the incision until the woman reports a distinct change in perception. The first point where a painful, sore, or sharp feeling appears is marked, and the distance to the incision is measured. If no change in sensation appears, stimulation is stopped at 0.5 cm from the incision. The area of secondary hyperalgesia is determined by testing along radial lines separated by 2.5 cm around the incision. The observations are translated onto graph paper, and the surface is calculated as the sum of the distances to the incision from points of hyperalgesia in cm divided by the cm length of the incision.</li>
 <li>Next, the pain threshold for mechanical static punctate stimuli is assessed using an electronic von Frey device. In brief, women are instructed to close their eyes during the procedure. An electronic von Frey filament is applied to the designated point on the skin (1 cm above the abdominal incision) and applications are separated by at least 30 seconds. Tactile pain threshold is defined as the smallest force (g/mm2) that is perceived as painful. Three determinations are made for each assessment and a mean is calculated.</li>
 </ol>
LONG-TERM FOLLOW-UP METHODS: 2, 6 AND 12-MONTH PAIN QUESTIONNAIRE
Part 9: Follow-up Pain Questionnaire via Telephone Interview 2, 6 &amp; 12 Months Postpartum
Lastly, a researcher calls subjects 2, 6 and 12 months after her cesarean section to administer the Short-form McGill Pain Questionnaire 2 and a customized questionnaire, which assesses post-operative pain experiences. This telephone interview usually takes no longer than 5 minutes.
Part 10: Representative Results 
To date, we performed mTS and DNIC pre-operatively in 75 women (n=38 in Brazil and n=37 in UWMC Seattle). Figure 1 shows graphic representation of pre-cesarean DNIC score.
<img src="/files/ftp_upload/1671/1671fig2.jpg" alt="Figure 1" /> Figure 1. DNIC score in Brazilian and North-American women scheduled for elective cesarean deliveries. Efficient endogenous analgesia is represented by positive DNIC score (0 to +5). Lack of endogenous analgesia is represented by negative DNIC score (0 to -5).
<img src="/files/ftp_upload/1671/1671fig3.jpg" alt="Figure 2" /> Figure 2. Correlation between pre-operative DNIC score/mTS and 48h wound hyperalgesia.

<ol>
	<li>Eisenach, J. C., Pan, P. H., Smiley, R., Lavand'homme, P., Landau, R., Houle, T. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Severity+of+acute+pain+after+childbirth,+but+not+type+of+delivery,+predicts+persistent+pain+and+postpartum.">Severity of acute pain after childbirth, but not type of delivery, predicts persistent pain and postpartum.</a> Pain. 140, 87-94 (2008).</li><li>Kehlet, H., Jensen, T. S., Woolf, C. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Persistent+postsurgical+pain:+risk+factors+and+prevention.">Persistent postsurgical pain: risk factors and prevention.</a> Lancet. 367, 1618-1625 (2006).</li><li>Ecker, J. L., Frigoletto, F. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cesarean+delivery+and+the+risk-benefit+calculus.">Cesarean delivery and the risk-benefit calculus.</a> N Engl J Med. 356, 885-888 (2007).</li><li>Carvalho, B., Cohen, S. E., Lipman, S. S., Fuller, A., Mathusamy, A. D., Macario, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Patient+preferences+for+anesthesia+outcomes+associated+with+cesarean+delivery.">Patient preferences for anesthesia outcomes associated with cesarean delivery.</a> Anesth Analg. 101, 1182-1187 (2005).</li><li>Yarnitsky, D., Crispel, Y., Eisenberg, E., Granovsky, Y., Ben-Nun, A., Sprecher, E., Best, L. A., Granot, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prediction+of+chronic+post-operative+pain:+pre-operative+DNIC+testing+identifies+patients+at+risk.">Prediction of chronic post-operative pain: pre-operative DNIC testing identifies patients at risk.</a> Pain. 138, 22-28 (2008).</li></ol>

Preliminary data reveals that mTS and DNIC may be correlated with greater post-cesarean hyperalgesia. If pre-operative mTS, DNIC, genetic testing and psychosocial questionnaires can predict individual susceptibility to develop severe post-operative pain and persistent pain, patients may be stratified to different risk groups. In return, different treatments including preemptive multimodal analgesia may have different outcomes in each subset of patients. <img src="/files/ftp_upload/1671/1671fig1.jpg" alt="Figure 3" /> Figure 3. Prediction of post-operative pain (PPOP project).

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<td>Pathway - Pain and Sensory Evaluation System</td>
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an experimental paradigm for the prediction of post-operative pain (ppop)

Many women undergo cesarean delivery without problems, however some experience significant pain after cesarean section. Pain is associated with negative short-term and long-term effects on the mother. Prior to women undergoing surgery, can we predict who is at risk for developing significant postoperative pain and potentially prevent or minimize its negative consequences? These are the fundamental questions that a team from the University of Washington, Stanford University, the Catholic University in Brussels, Belgium, Santa Joana Women's Hospital in S&atilde;o Paulo, Brazil, and Rambam Medical Center in Israel is currently evaluating in an international research collaboration. The ultimate goal of this project is to provide optimal pain relief during and after cesarean section by offering individualized anesthetic care to women who appear to be more 'susceptible' to pain after surgery.
A significant number of women experience moderate or severe acute post-partum pain after vaginal and cesarean deliveries. 1 Furthermore, 10-15% of women suffer chronic persistent pain after cesarean section. 2 With constant increase in cesarean rates in the US 3 and the already high rate in Brazil, this is bound to create a significant public health problem. When questioning women's fears and expectations from cesarean section, pain during and after it is their greatest concern. 4 Individual variability in severity of pain after vaginal or operative delivery is influenced by multiple factors including sensitivity to pain, psychological factors, age, and genetics. The unique birth experience leads to unpredictable requirements for analgesics, from 'none at all' to 'very high' doses of pain medication. Pain after cesarean section is an excellent model to study post-operative pain because it is performed on otherwise young and healthy women. Therefore, it is recommended to attenuate the pain during the acute phase because this may lead to chronic pain disorders. The impact of developing persistent pain is immense, since it may impair not only the ability of women to care for their child in the immediate postpartum period, but also their own well being for a long period of time.
In a series of projects, an international research network is currently investigating the effect of pregnancy on pain modulation and ways to predict who will suffer acute severe pain and potentially chronic pain, by using simple pain tests and questionnaires in combination with genetic analysis. A relatively recent approach to investigate pain modulation is via the psychophysical measure of Diffuse Noxious Inhibitory Control (DNIC). This pain-modulating process is the neurophysiological basis for the well-known phenomenon of 'pain inhibits pain' from remote areas of the body. The DNIC paradigm has evolved recently into a clinical tool and simple test and has been shown to be a predictor of post-operative pain.5 Since pregnancy is associated with decreased pain sensitivity and/or enhanced processes of pain modulation, using tests that investigate pain modulation should provide a better understanding of the pathways involved with pregnancy-induced analgesia and may help predict pain outcomes during labor and delivery. For those women delivering by cesarean section, a DNIC test performed prior to surgery along with psychosocial questionnaires and genetic tests should enable one to identify women prone to suffer severe post-cesarean pain and persistent pain. These clinical tests should allow anesthesiologists to offer not only personalized medicine to women with the promise to improve well-being and satisfaction, but also a reduction in the overall cost of perioperative and long term care due to pain and suffering. On a larger scale, these tests that explore pain modulation may become bedside screening tests to predict the development of pain disorders following surgery.

Watch this Scientific Journal Video about An Experimental Paradigm for the Prediction of Post-Operative Pain PPOP at JoVE.com

An Experimental Paradigm for the Prediction of Post-Operative Pain PPOP

Diffuse noxious inhibitory control, temporal summation and wound hyperalgesia testing are demonstrated in the obstetric patient. These tests evaluate inhibitory and excitatory mechanisms of pain processing and are here utilized to evaluate endogenous analgesia at different time-points during pregnancy and the peripartum period to help reveal individual s risk for persistent pain.

An Experimental Paradigm for the Prediction of Post-Operative Pain (PPOP)

Many women undergo cesarean delivery without problems, however some experience significant pain after cesarean section. Pain is associated with negative ...

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21.2K Views.  University of Washington School of Medicine. Diffuse noxious inhibitory control, temporal summation and wound hyperalgesia testing are demonstrated in the obstetric patient. These tests evaluate inhibitory and excitatory mechanisms of pain processing and are here utilized to evaluate endogenous analgesia at different time-points during pregnancy and the peripartum period to help reveal individual s risk for persistent pain.

Video: An Experimental Paradigm for the Prediction of Post-Operative Pain PPOP

Intraoperative Detection of Subtle Endometriosis: A Novel Paradigm for Detection and Treatment of Pelvic Pain Associated with the Loss of Peritoneal Integrity

Endometriosis is a common disease affecting 40 to 70% of reproductive-aged women with chronic pelvic pain (CPP) and/or infertility. The purpose of this study was to demonstrate the use of a blue dye (methylene blue) to stain peritoneal surfaces during laparoscopy (L/S) to detect the loss of peritoneal integrity in patients with pelvic pain and suspected endometriosis. Forty women with CPP and 5 women without pain were evaluated in this pilot study. During L/S, concentrated dye was sprayed onto peritoneal surfaces, then aspirated and rinsed with Lactated Ringers solution. Areas of localized dye uptake were evaluated for the presence of visible endometriotic lesions. Areas of intense peritoneal staining were resected and some fixed in 2.5% buffered gluteraldehyde and examined by scanning (SEM) electron microscopy. Blue dye uptake was more common in women with endometriosis and chronic pelvic pain than controls (85% vs. 40%). Resection of the blue stained areas revealed endometriosis by SEM and loss of peritoneal cell-cell contact compared to normal, non-staining peritoneum. Affected peritoneum was associated with visible endometriotic implants in most but not all patients. Subjective pain relief was reported in 80% of subjects. Based on scanning electron microscopy, we conclude that endometrial cells extend well beyond visible implants of endometriosis and appear to disrupt the underlying mesothelium. Subtle lesions of endometriosis could therefore cause pelvic pain by disruption of peritoneal integrity, allowing menstrual or ovulatory blood and associated pain factors access to underlying sensory nerves. Complete resection of affected peritoneum may provide a better long-term treatment for endometriosis and CPP. This simple technique appears to improve detection of subtle or near invisible endometriosis in women with CPP and minimal visual findings at L/S and may serve to elevate diagnostic accuracy for endometriosis at laparoscopy.

Loss of peritoneal integrity provides a new paradigm to understand and treat chronic pelvic pain in women with mild forms of endometriosis and can be easily detected using intraoperative instillation of dye at the time of laparoscopy.

Endometriosis is a  common disease affecting 40 to 70% of reproductive-aged women with chronic  pelvic pain (CPP) and/or infertility. The purpose of this ...

An Ex vivo Model to Study Hormone Action in the Human Breast

The study of hormone action in the human breast has been hampered by lack of adequate model systems. Upon in vitro culture, primary mammary epithelial cells tend to lose hormone receptor expression. Widely used hormone receptor positive breast cancer cell lines are of limited relevance to the in vivo situation. Here, we describe an ex vivo model to study hormone action in the human breast. Fresh human breast tissue specimens from surgical discard material such as reduction mammoplasties or mammectomies are mechanically and enzymatically digested to obtain tissue fragments containing ducts and lobules and multiple stromal cell types. These tissue microstructures kept in basal medium without growth factors preserve their intercellular contacts, the tissue architecture, and remain hormone responsive for several days. They are readily processed for RNA and protein extraction, histological analysis or stored in freezing medium. Fluorescence activated cell sorting (FACS) can be used to enrich for specific cell populations. This protocol provides a straightforward, standard approach for translational studies with highly complex, varied human specimens.

An Ex vivo Model to Study Hormone Action in the Human Breast

We have developed a novel ex vivo model to study hormone action in the human breast. It is based on tissue microstructures isolated from surgical breast tissue specimens which preserve tissue architecture, intercellular interactions, and paracrine signaling.

The study of hormone action in the human breast has been hampered by lack of adequate model systems. Upon in vitro culture, primary mammary epithelial ...

The Monoiodoacetate Model of Osteoarthritis Pain in the Mouse

A major symptom of patients with osteoarthritis (OA) is pain that&#160;is triggered by peripheral as well as central changes within the pain pathways. The current treatments for OA pain such as NSAIDS or opiates are neither sufficiently effective nor devoid of detrimental side effects. Animal models of OA are being developed to improve our understanding of OA-related pain mechanisms and define novel pharmacological targets for therapy. Currently available models of OA in rodents include surgical and chemical interventions into one knee joint. The monoiodoacetate (MIA) model has become a standard for modelling joint disruption in OA in both rats and mice. The model, which is easier to perform in the rat, involves injection of MIA into a knee joint that induces rapid pain-like responses in the ipsilateral limb, the level of which can be controlled by injection of different doses. Intra-articular injection of MIA disrupts chondrocyte glycolysis by inhibiting glyceraldehyde-3-phosphatase dehydrogenase and results in chondrocyte death, neovascularization, subchondral bone necrosis and collapse, as well as inflammation. The morphological changes of the articular cartilage and bone disruption are reflective of some aspects of patient pathology. Along with joint damage, MIA injection induces referred mechanical sensitivity in the ipsilateral hind paw and weight bearing deficits that are measurable and quantifiable. These behavioral changes resemble some of the symptoms reported by the patient population, thereby validating the MIA injection in the knee as a useful and relevant pre-clinical model of OA pain.
The aim of this article is to describe the methodology of intra-articular injections of MIA and the behavioral recordings of the associated development of hypersensitivity with a mind to highlight the necessary steps to give consistent and reliable recordings.

Osteoarthritis (OA), or degenerative joint disease, is a debilitating condition associated with pain that remains only partially controlled by available analgesics. Animal models are being developed to improve our understanding of OA-related pain mechanisms. Here we describe the methodology for the monoiodoacetate model of OA pain in the mouse.

A major symptom of patients with osteoarthritis (OA) is pain that&#160;is triggered by peripheral as well as central changes within the pain pathways. The ...

An Improved Method for Rapid Intubation of the Trachea in Mice

Despite some anatomical and physiological differences, mouse models continue to be an essential tool for studying human lung disease. Bleomycin toxicity is a commonly used model to study both acute lung injury and fibrosis, and multiple methods have been developed for administering bleomycin (and other toxic agents) into the lungs. However, many of these approaches, such as transtracheal instillation, have inherent drawbacks, including the need for strong anesthetics and survival surgery. This paper reports a quick, reproducible method of intratracheal intubation that involves mild inhaled anesthesia, visualization of the trachea, and the use of a surrogate spirometer to confirm exposure. As a proof of concept, 8-12 week old C57BL/6 mice were administered either 2.0 U/kg of bleomycin or an equivalent volume of PBS, and both damage and fibrotic endpoints were measured post-exposure. This procedure allows researchers to treat a large cohort of mice in a relatively short period with little expense and minimal post-procedure care.

This article presents a rapid and simple method for administering bleomycin directly into the mouse trachea via intubation. Key advantages of this method are that it is highly reproducible, easy to master, and does not require specialized equipment or lengthy recovery times.

Despite some anatomical and physiological differences, mouse models continue to be an essential tool for studying human lung disease. Bleomycin toxicity ...

Analyzing Beneficial Effects of Nutritional Supplements on Intestinal Epithelial Barrier Functions During Experimental Colitis

Inflammatory bowel diseases (IBD), including Crohn&#39;s disease and ulcerative colitis, are chronic relapsing disorders of the intestines. They cause severe problems, such as abdominal cramping, bloody diarrhea, and weight loss, in affected individuals. Unfortunately, there is no cure yet, and treatments only aim to alleviate symptoms. Current treatments include anti-inflammatory and immunosuppressive drugs that may cause severe side effects. This warrants the search for alternative treatment options, such as nutritional supplements, that do not cause side effects. Before their application in clinical studies, such compounds must be rigorously tested for effectiveness and security in animal models. A reliable experimental model is the dextran sulfate sodium (DSS) colitis model in mice, which reproduces many of the clinical signs of ulcerative colitis in humans. We recently applied this model to test the beneficial effects of a nutritional supplement containing vitamins C and E, L-arginine, and &#969;3-polyunsaturated fatty acids (PUFA). We analyzed various disease parameters and found that this supplement was able to ameliorate edema formation, tissue damage, leukocyte infiltration, oxidative stress, and the production of pro-inflammatory cytokines, leading to an overall improvement in the disease activity index. In this article, we explain in detail the correct application of nutritional supplements using the DSS colitis model in C57Bl/6 mice, as well as how disease parameters such as histology, oxidative stress, and inflammation are assessed. Analyzing the beneficial effects of different diet supplements may then eventually open new avenues for the development of alternative treatment strategies that alleviate IBD symptoms and/or that prolong the phases of remission without causing severe side effects.

Current treatments of inflammatory bowel diseases (IBD) aim at alleviating disease symptoms but may cause severe side effects. Thus, alternative strategies are being investigated in animal colitis models. Here, we explain how the beneficial effects of diet supplements on clinical IBD signs are analyzed in such a colitis model.

Inflammatory bowel diseases (IBD), including Crohn&#39;s disease and ulcerative colitis, are chronic relapsing disorders of the intestines. They cause ...

A Quantitative Sensory Testing Paradigm to Obtain Measures of Pain Processing in Patients Undergoing Breast Cancer Surgery

Chronic pain following surgery, persistent postsurgical pain, is an important highly prevalent condition contributing to significant symptom burden and lower quality of life. Persistent postsurgical pain is relatively refractory to treatment hence generating a high need for preventive strategies and treatments. Therefore, the identification of patients at risk of developing persistent pain is an area of active ongoing research. Recently it was demonstrated that peri-operative disruptions in central pain processing may be able to predict persistent postsurgical pain at long term follow-up in breast cancer patients. The aim of the current report is to present a short protocol to obtain pain thresholds to different stimuli at multiple sites and a measure of endogenous analgesia in breast cancer patients. We have used this method successfully in a clinical context and detail some representative results from a clinical study.

Persistent postsurgical pain may be related to changes in pain processing. By assessing pain in response to standardized stimuli, changes in pain processing can be elucidated. We present methods to obtain pain thresholds to different stimuli and a measure of endogenous analgesia in patients undergoing breast cancer surgery.

Chronic pain following surgery, persistent postsurgical pain, is an important highly prevalent condition contributing to significant symptom burden and ...

Assessment of Static Graviceptive Perception in the Roll-Plane using the Subjective Visual Vertical Paradigm

Vestibular disorders are among the most common syndromes in medicine. In recent years, new vestibular diagnostic systems have been introduced that allow the examination of all semicircular canals in the clinical setting. Assessment methods of the otolithic system, which is responsible for the perception of linear acceleration and perception of gravity, are far less in clinical use. There are several experimental approaches for measuring the perception of gravity. The most frequently used method is the determination of the subjective visual vertical. This is usually measured with the head in an upright position. We present here an assessment method for testing otolith function in the roll plane. The subjective visual vertical is measured in the head upright position as well as with head inclination of &#177; 15&#176; and &#177; 30&#176; in the roll plane. This extended functional paradigm is an easy-to-perform clinical test of otolith function and ensures increased information content for the detection of impaired graviceptive perception.

The perception of gravity is commonly determined by the subjective visual vertical in the head upright position. The additional assessment at head tilts of &#177; 15&#176; and &#177; 30&#176; in the roll plane ensures increased information content for the detection of impaired graviceptive perception.

Vestibular disorders are among the most common syndromes in medicine. In recent years, new vestibular diagnostic systems have been introduced that allow ...

Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma

We aimed to study the mechanism of Trichosanthes-Fritillaria thunbergii in treating lung adenocarcinoma (LUAD) based on network pharmacology and experimental verification. The effective components and potential targets of Trichosanthis and Fritillaria thunbergii were collected by high-throughput experiment and reference-guided (HERB) database of traditional Chinese medicine and a similarity ensemble approach (SEA) database, and the LUAD-related targets were queried by the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. A drug-component-disease-target network was constructed by Cytoscape software. Protein-protein interaction (PPI) network, gene ontology (GO) function, and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were conducted to obtain core targets and key pathways. An aqueous extract of Trichosanthes-Fritillaria thunbergii and A549 cells were used for the subsequent experimental validation. Through the HERB database and literature search, 31 effective compounds and 157 potential target genes of Trichosanthes-Fritillaria thunbergii were screened, of which 144 were regulatory targets of Trichosanthes-Fritillaria thunbergii in the treatment of lung adenocarcinoma. The GO functional enrichment analysis showed that the mechanism of action of Trichosanthes-Fritillaria thunbergii against lung adenocarcinoma is mainly protein phosphorylation. The KEGG pathway enrichment analysis suggested that the treatment of lung adenocarcinoma by Trichosanthes-Fritillaria thunbergii mainly involves the PI3K/AKT signaling pathway. The experimental validation showed that an aqueous extract of Trichosanthes-Fritillaria thunbergii could inhibit the proliferation of A549 cells and the phosphorylation of AKT. Through network pharmacology and experimental validation, it was verified that the PI3K/AKT signaling pathway plays a vital role in the action of Trichosanthes-Fritillaria thunbergii in treating lung adenocarcinoma.

Network Pharmacology Prediction and Experimental Validation of Trichosanthes-Fritillaria thunbergii Action Mechanism Against Lung Adenocarcinoma

This study reveals the mechanism of Trichosanthes-Fritillaria thunbergii in treating lung adenocarcinoma based on network pharmacology and experimental verification. The study also demonstrates that the PI3K/AKT signaling pathway plays a vital role in the action of Trichosanthes-Fritillaria thunbergii in treating lung adenocarcinoma.

We aimed to study the mechanism of Trichosanthes-Fritillaria thunbergii in treating lung adenocarcinoma (LUAD) based on network pharmacology and ...

Quantitative Analysis of Liver Stiffness Distribution

A Three-Dimensional Digital Model for Early Diagnosis of Hepatic Fibrosis Based on Magnetic Resonance Elastography

Hepatic fibrosis is an early stage of liver cirrhosis, and there are no better non-invasive and convenient methods for the detection and evaluation of the disease. Despite the good progress made with the liver stiffness map (LSM) based on magnetic resonance elastography (MRE), there are still some limitations that need to be overcome, including manual focus determination, manual selection of regions of interest (ROIs), and discontinuous LSM data without structural information, which makes it impossible to evaluate the liver as a whole. In this study, we propose a novel three-dimensional (3D) digital model for the early diagnosis of hepatic fibrosis based on MRE.
MRE is a non-invasive imaging technique that employs magnetic resonance imaging (MRI) to measure the liver stiffness at the scanning site through human-computer interaction. Studies have indicated a significant positive correlation between the LSM obtained through MRE and the degree of hepatic fibrosis. However, for clinical purposes, a comprehensive and precise quantification of the degree of hepatic fibrosis is necessary. To address this, the concept of Liver Stiffness Distribution (LSD) was proposed in this study, which refers to the 3D stiffness volume of each liver voxel obtained by the alignment of 3D liver tissue images and MRE indicators. This provides a more effective clinical tool for the diagnosis and treatment of hepatic fibrosis.

Author Spotlight: Advancing Hepatic Fibrosis Diagnosis Using Magnetic Resonance Elastography and AI 

The objective of this study was to develop a novel three-dimensional digital model for the early diagnosis of hepatic fibrosis, which includes the stiffness of each voxel in the patient's liver and can thus, be used to calculate the distribution ratio of the patient's liver at different fibrosis stages.

Hepatic fibrosis is an early stage of liver cirrhosis, and there are no better non-invasive and convenient methods for the detection and evaluation of the ...

Procedure for Targeted Muscle Reinnervation for Treating Postamputation Pain

Targeted Muscle Reinnervation: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain

Over the past decade, the field of prosthetics has witnessed significant progress, particularly in the development of surgical techniques to enhance the functionality of prosthetic limbs. Notably, novel surgical interventions have had an additional positive outcome, as individuals with amputations have reported neuropathic pain relief after undergoing such procedures. Subsequently, surgical techniques have gained increased prominence in the treatment of postamputation pain, including one such surgical advancement - targeted muscle reinnervation (TMR). TMR involves a surgical approach that reroutes severed nerves as a type of nerve transfer to &#34;target&#34; motor nerves and their accompanying motor end plates within nearby muscles. This technique originally aimed to create new myoelectric sites for amplified electromyography (EMG) signals to enhance prosthetic intuitive control. Subsequent work showed that TMR also could prevent the formation of painful neuromas as well as reduce postamputation neuropathic pain (e.g., Residual and Phantom Limb Pain). Indeed, multiple studies have demonstrated TMR&#39;s effectiveness in mitigating postamputation pain as well as improving prosthetic functional outcomes. However, technical variations in the procedure have been identified as it is adopted by clinics worldwide. The purpose of this article is to provide a detailed step-by-step description of the TMR procedure, serving as the foundation for an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394), including nine clinics in seven countries. In this trial, TMR and two other surgical techniques for managing postamputation pain will be evaluated.

Author Spotlight: Advancements and Challenges in Surgical Treatments for Postamputation Pain

The protocol outlines the surgical procedure&#160;for the treatment of postamputation pain using Targeted Muscle Reinnervation (TMR). TMR will be compared with two other surgical techniques, specifically Regenerative Peripheral Nerve Interface (RPNI) and neuroma excision, followed by immediate burying within muscle under the context of an international, randomized controlled trial.

Over the past decade, the field of prosthetics has witnessed significant progress, particularly in the development of surgical techniques to enhance the ...