Chu et al. (2015)
The study reviewed 14 clinical studies that used quantitative sensory testing to detect hyperalgesia in chronic pain patients on long-term opioids. Most sensory modalities tested, including cold, heat, pressure, electrical, ischemic, and injection pain, failed to demonstrate hypersensitivity to test stimuli. Heat pain sensitivity showed some promising results in detecting hyperalgesia, but none of the measures reviewed met the criteria as a definitive standard. Additional studies with improved designs are needed.
A Systematic Review on the Efficacy of Iontophoresis
as a Treatment for Lateral Epicondylitis by James McKivigan*, Brent Yamashita and Derek Smith in Research & Investigations in Sports Medicine
Systematic reviews of complementary therapies – an annotated bibliography. Pa...home
Complementary therapies are widespread but controversial. We aim to provide a
comprehensive collection and a summary of systematic reviews of clinical trials in three major
complementary therapies (acupuncture, herbal medicine, homeopathy). This article is dealing with
homeopathy. Potentially relevant reviews were searched through the register of the Cochrane
Complementary Medicine Field, the Cochrane Library, Medline, and bibliographies of articles and
books. To be included articles had to review prospective clinical trials of homeopathy; had to
describe review methods explicitly; had to be published; and had to focus on treatment effects.
Information on conditions, interventions, methods, results and conclusions was extracted using a
pretested form and summarized descriptively.
A Systematic Review on the Efficacy of Iontophoresis
as a Treatment for Lateral Epicondylitis by James McKivigan*, Brent Yamashita and Derek Smith in Research & Investigations in Sports Medicine
Systematic reviews of complementary therapies – an annotated bibliography. Pa...home
Complementary therapies are widespread but controversial. We aim to provide a
comprehensive collection and a summary of systematic reviews of clinical trials in three major
complementary therapies (acupuncture, herbal medicine, homeopathy). This article is dealing with
homeopathy. Potentially relevant reviews were searched through the register of the Cochrane
Complementary Medicine Field, the Cochrane Library, Medline, and bibliographies of articles and
books. To be included articles had to review prospective clinical trials of homeopathy; had to
describe review methods explicitly; had to be published; and had to focus on treatment effects.
Information on conditions, interventions, methods, results and conclusions was extracted using a
pretested form and summarized descriptively.
Homeopathy in the treatment of fibromyalgia A comprehensive literature-review...home
Given the low number and included trials and the lowmethodological quality, any conclusion based on the resultsof this review have to be regarded as preliminary. However,as single case studies and clinical trials indicate a positiveeffect, homeopathy could be considered a complementarytreatment for patients with fibromyalgia
Homeopathic treatment of patients with chronic sinusitis: A prospective obser...home
This observational study showed relevant improvements that persisted for 8 years
in patients seeking homeopathic treatment because of sinusitis. The extent to which the observed
effects are due to the life-style regulation and placebo or context effects associated with the
treatment needs clarification in future explanatory studies.
Comparative evaluation of 2g single dose versus conventional dose azithromycin in uncomplicated skin and skin structure infections. Indian Journal Of Pharmacology. August 2015;Vol. 47; Issue 4
Homeopathy in the treatment of fibromyalgia A comprehensive literature-review...home
Given the low number and included trials and the lowmethodological quality, any conclusion based on the resultsof this review have to be regarded as preliminary. However,as single case studies and clinical trials indicate a positiveeffect, homeopathy could be considered a complementarytreatment for patients with fibromyalgia
Homeopathic treatment of patients with chronic sinusitis: A prospective obser...home
This observational study showed relevant improvements that persisted for 8 years
in patients seeking homeopathic treatment because of sinusitis. The extent to which the observed
effects are due to the life-style regulation and placebo or context effects associated with the
treatment needs clarification in future explanatory studies.
Comparative evaluation of 2g single dose versus conventional dose azithromycin in uncomplicated skin and skin structure infections. Indian Journal Of Pharmacology. August 2015;Vol. 47; Issue 4
The paper lists the correct method of diagnosing chronic pain, and matching the proper medication to tissue damage without the use of narcotics or opioids.
Predicting Medical Test Results and Intra-Operative Findings in Chronic Pain ...Nelson Hendler
The Pain Validity Test can predict which patient will have abnormal medical test results with 95% accuracy, and surgical abnormalities with 94% accuracy. This on-line questionnaire takes only 5 minutes of staff time to administer, and takes only 15 minutes of patient time.Results are available immediately. This test can be used to document "medical necessity" for insurance pre-authorization for testing and surgery.
ORIGINAL ARTICLE HIP - ANESTHESIAA randomized controlled.docxgerardkortney
ORIGINAL ARTICLE � HIP - ANESTHESIA
A randomized controlled trial of postoperative analgesia following
total knee replacement: transdermal Fentanyl patches
versus patient controlled analgesia (PCA)
M. J. Hall1 • S. M. Dixon2 • M. Bracey3 • P. MacIntyre4 • R. J. Powell3 •
A. D. Toms3
Received: 13 November 2014 / Accepted: 12 February 2015 / Published online: 11 March 2015
� Springer-Verlag France 2015
Abstract
Background This randomized controlled trial compared a
standard patient controlled analgesic (PCA) regime with a
transdermal and oral Fentanyl regime for post-operative
pain management in patients undergoing total knee
replacement.
Methods One hundred and ninety-six patients undergoing
total knee replacement were recruited. Pre- and post-op-
eratively Visual Analogue Score (VAS), Oxford Knee
Score, Health Anxiety and Depression Score and Brief Pain
Inventory Score were completed. According to the day 1,
VAS score patients were randomly allocated to either a
PCA regime or a Fentanyl transdermal/oral regime. Patient
reported outcomes were measured until the patients were
discharged.
Results The results demonstrate that in terms of analgesic
effect, day of discharge and side effect profile the two
regimes are comparable.
Conclusions We conclude that a Fentanyl transdermal
regime provides adequate analgesic effect comparable to a
standard PCA regime in conjunction with a low side effect
profile. Using a transdermal analgesic system provides ef-
ficient continuous delivery enabling a smooth transition
from hospital to home within the first week. Transdermal
Fentanyl provides an alternative analgesic regime that can
provide an equivalent analgesic effect so as to enable a
satisfactory outcome for the patient in terms of function
and pain.
Level of evidence II.
Keywords Total knee replacement � Post-operative
analgesia � Patient controlled analgesia � Fentanyl patches
Introduction
Knee replacement surgery has proved a successful and
cost-effective method for relieving pain and restoring
function in patients with osteoarthritis [1]. However, pain
management after knee replacement surgery remains a
significant problem, with patients reporting this as a major
concern prior to surgery [2]. Implementing relevant pre-
operative screening methods may facilitate the identifica-
tion of individuals at high risk of experiencing high post-
operative pain [3]. Despite recent advances in the aetiology
of pain, improved pain treatments and the development of
clinical guidelines for pain assessment, the under-treatment
of post-operative pain remains a challenge to both surgeon
and anaesthetist. Recent studies have clearly demonstrated
that patient satisfaction following total knee replacement is
multifactorial with the most significant predictor of dis-
satisfaction being a painful total knee replacement [1].
Providing effective pain relief in the post-operative pe-
riod is essential to enable early mobili.
Les NVPO sont un événement fréquent en post-anesthésie puisqu'ils touchent environ un tiers des patients. Les différents scores et prophylaxies utilisées bien que souvent efficaces ne closent pas le chapitre de leur prévention. La gabapentine, antivonvusilvant, a montré par ailleurs son effet analgésique en post-opératoire.
Plus récemment, la gabapentine a montré un effet anti-émétique lorsqu'elle était administrée en prévention dans la chimiothérapie du cancer du sein.
Cette étude est une méta-analyse des essais randomisés de la gabapentine en prévention des NVPO. Elle conclut à son efficacité, efficacité d'autant plus marquée que le propofol n'est pas utilisé comme agent d'induction et/ou d'entretien.
Le degré de relâchement musculaire en chirurgie coelioscopique de la vésicule biliaire fait partie du quotidien des discussions entre anesthésistes et chirurgiens au bloc opératoire. Au fond tous sont convaincus de l'efficacité du curare : le chirurgien qui le demande et l'anesthésiste qui pense lui à sa décurarisation.
Cette étude teste curarisation profonde versus curarisation de routine dans la chirurgie coelioscopique de la vésicule biliaire. Avec comme première question "est-ce qu'une curarisation profonde permet de travaillert avec une pression abdominable moindre?", pression dont on sait qu'elle est pourvoyeuse de douleur post-opératoire.
La réponse est que le degré de curarisation participe de façon marginale au confort du chirurgien... et ne permet pas plus fréquemment de travailler à pression abdominale basse.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
2. Anesthesiology 2015; 122:677-85 678 Katz et al.
Measures of Opioid-induced Hyperalgesia in Chronic Pain
beyond the scope of this review which focuses on patients
who are maintained on long-term opioid therapy.
To determine whether clinical OIH exists and to char-
acterize it, researchers have aimed at developing laboratory
methods to measure hyperalgesia (i.e., the increase in pain sen-
sitivity, as a proxy to clinical OIH) in chronic pain patients
on long-term opioids, outside of the patient’s primary clinical
pain syndrome. To this end, laboratory methods have been
developed that consist of evaluating patients’ pain thresh-
old and tolerance to external experimental stimuli such as
mechanical (pressure, touch, or injection), thermal (cold/
heat), electrical, or other stimuli (e.g., ischemia). Two pos-
sible study designs have been typically used (1) patients with
chronic pain on long-term opioids are cross-sectionally com-
pared with patients with the same chronic pain syndrome
not taking opioids, or (2) patients with chronic pain on
long-term opioids are evaluated before and after an interven-
tion such as discontinuing opioid therapy. However, none of
these experimental approaches have been validated or is con-
sidered the definitive standard for measuring hyperalgesia in
clinical trials of pain patients on chronic opioids. A suitable
method for evaluating hyperalgesia would be reliable and
responsive, that is, able to discriminate groups of patients
known to have different levels of pain sensitivity that may
be associated with opioid therapy. Therefore, we conducted
a systematic review of clinical studies that incorporated mea-
sures of hyperalgesia in chronic pain patients on long-term
opioids to determine and compare the performance of each
method to measure hyperalgesia. Because responsiveness
requires reliability, we have focused on responsiveness as
the key performance characteristic for this review. Finding
adequate experimental methods to measure hyperalgesia in
chronic pain patients will help determine whether clinical
OIH exist, to characterize it, and to prevent or treat it.
Materials and Methods
Literature Search
To find human studies that measure hyperalgesia in patients
on long-term opioids for chronic pain, a search in PubMed
and Cochrane databases was performed using terms (“all
terms” search) such as “opioid induced hyperalgesia,” “study
or trial,” and “long-term or chronic,” and rejecting the terms
“mice or rodent.” A first screening of the retrieved articles was
performed based on the title and abstract; the screened articles
were then retrieved in their full version and carefully read to
be included in the final selection. In order for an article to be
selected, the study had to meet the following criteria: (1) be a
randomized controlled trial, a prospective study, or a cross-sec-
tional comparative study; (2) be conducted in patients on long-
term opioids for chronic pain (single-dose/acute studies and
studies conducted only in healthy volunteers were excluded);
(3) include assessments or measures of hyperalgesia as part of
the study; and (4) be published in English. The search included
articles up to May 2014 (no date limit was used).
The methods used to measure hyperalgesia in the articles
retrieved from the main search were compiled. To ensure
that all possible original articles were found, a secondary
literature search was conducted using the terms “opioid
induced hyperalgesia” and the name of the test used to mea-
sure hyperalgesia (e.g., cold pressor test, thermal sensory ana-
lyzer, lidocaine injection, electrical stimulation, etc.).
Data Analysis
Data extracted from the articles included the type of study
(studies were categorized into randomized controlled tri-
als, prospective controlled studies, prospective uncontrolled
studies, and cross-sectional comparative studies), the patient
population, the measure(s)/test(s) used to assess hyperalge-
sia, available results (difference between pre- and posttreat-
ment, difference between groups, dose-related data, and any
other relevant data), and P values (when available).
Results
Search Results
The article screening and selection process is illustrated in
figure 1. The PubMed Library search retrieved 62 articles
and the Cochrane database search retrieved 22; a search of
our personal records retrieved 1 article. After elimination of
duplicates, 68 articles were screened for relevance. A total
of 11 articles made the final selection (from most to least
recent): Suzan et al.,5
Chu et al.,6
Krishnan et al.,7
Edwards
et al.,8
Wang et al.,9
Hooten et al.,10
Chen et al.,11
Ram
et al.12
Hay et al.,13
Cohen et al.,14
and Chu et al.15
Search-
ing the references of these articles retrieved two other articles
(Reznikov et al.16
[cited in Suzan et al.5
]; Doverty et al.17
[cited in Chu et al.6
]). Another original article was found via
the secondary search for OIH and lidocaine injection (Kim
et al.18
). Thus, a total of 14 original studies that measured
hyperalgesia in patients on long-term opioids for chronic
pain were found.
Description of Studies
Of the 14 selected studies, 1 was a randomized controlled
trial,6
1 was a prospective controlled study,5
3 were prospec-
tive uncontrolled studies,9,10,15
and 9 were cross-sectional
observation studies.7,8,11–14,16–18
Six hyperalgesia measure-
ment paradigms were used in these studies: cold pain, heat
pain, pressure pain, electrical pain, ischemic pain, and injec-
tion pain; these methods are described in table 1. The design,
patient population, and results of each study are summarized
in table 2.
Summary of Findings
The ideal measure would be able to differentiate pain sen-
sitivity in patients randomly exposed prospectively to opi-
oids compared with a cohort randomly assigned to a control
condition. Only one study6
used such a design (randomized
controlled trial), and the two experimental methods used in
that study (cold pain threshold and tolerance using ice water
Downloaded From: http://anesthesiology.pubs.asahq.org/pdfaccess.ashx?url=/data/Journals/JASA/932777/ by Samir Sharsharr on 02/25/2015
3. Anesthesiology 2015; 122:677-85 679 Katz et al.
PAIN MEDICINE
Fig. 1. Search result flow diagram.
Table 1. Summary of the Methods Used to Measure OIH
Type of
Stimulation Test Name Methodology and Measurements References
Cold pain Cold pressor test The subject’s hand is submerged up to the wrist in a 0.5°–1°C ice water
bath continuously recirculated by a pump (up to 120 s). Measures are
time to pain detection (threshold) and to intolerable pain (withdrawal of
the hand; tolerance); continuous pain scores. Painful cold water immer-
sion was used as the conditioning stimulus in a CPM paradigm.
Chu et al.,15
Chu
et al.,6
Hay et al.,13
Suzan et al.5
Heat pain Medoc TSA
(Medoc Ltd.
Advanced Med-
ical Systems,
Ramat Yishai,
Israel)
Quantitative pain threshold is determined with the method of limits with the
Medoc TSA. A thermode is applied to the skin and heat is applied at various
temperatures. Measures are pain threshold and pain tolerance (in °C); pain
scores at various temperatures; temporal summation of suprathreshold
heat stimuli (in a few studies); ratings of heat pain intensity used as the test
stimulus in a CPM paradigm.
Reznikov et al.,16
Chu
et al.,15
Chu et al.,6
Suzan et al.,5
Chen
et al.,11
Edwards
et al.8
Pressure
pain
Pressure algom-
eter
A manual pressure algometer (e.g., a 3-mm diameter paddle algometer;
Medical-Hako, Hamburg, Germany) is pressed perpendicularly to the
skin at selected points and increasing pressure is applied. Measures are
time to perception of a painful sensation (threshold); the measurement is
shown on an algometer scale.
Reznikov et al.16
Electrical
pain
Electrical stimula-
tion of ear lobe
Voltage is applied to ear lobe starting at 0 V and increasing at a constant
rate of 2 V every 1.4 s, up to a maximum of 100 V. Measures are pain
threshold and pain tolerance (in volts).
Doverty et al.,17
Krishnan et al.,7
Hay et al.13
Ischemic
pain
Blood pres-
sure cuff test
with handgrip
exercise
A blood pressure cuff is placed around the nondominant arm of the subject
and the pressure is increased to 20 mmHg above the subject’s systolic
pressure. With the pressure maintained, subjects perform a handgrip
exercise on an elastic ball, in accordance with the rhythm of a metro-
nome (subject’s eyes are covered to minimize distraction and time cues).
Measures are time to feeling of pain (pain threshold); time to untolerable
pain (to a maximum of 5 min) (pain tolerance).
Krishnan et al.,7
Ram
et al.12
Injection
pain
Subcutaneous
local anes-
thetic injection
A local anesthetic (generally lidocaine) is administered subcutaneously (before
a full dose of anesthetic for a procedure). Measures are subject’s ratings of
pain and unpleasantness of the lidocaine injection.
Cohen et al.14
CPM = conditioned pain modulation; OIH = opioid-induced hyperalgesia; TSA = thermal sensory analyzer.
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8. Anesthesiology 2015; 122:677-85 684 Katz et al.
Measures of Opioid-induced Hyperalgesia in Chronic Pain
immersion and heat pain threshold and tolerance using the
Medoc TSA; Medoc Ltd. Advanced Medical Systems, Ramat
Yishai, Israel) both failed to differentiate the two groups. It
is unclear whether these approaches failed because of the
measures, because the patients did not in fact develop hyper-
algesia, or because treatment was short term and used rela-
tively low doses. Thus, no measure of hyperalgesia can claim
definitive standard status.
Table 3 summarizes the test results by indicating which
measures were used in each study, and whether the P value
for the between-group difference tested was greater than
0.05 (−) or less than 0.05 (+). The major methods that have
been used are (1) cold pain threshold and tolerance using ice
water immersion, and (2) heat pain threshold, tolerance, or
intensity at suprathreshold stimulus levels using computer-
controlled thermode devices. The summary results in table 3
suggest that, on average, none of the stimuli were capable of
detecting hyperalgesia in chronic pain patients on long-term
opioids. However, some specific findings merit attention.
For instance, two controlled prospective studies5,6
and one
uncontrolled prospective study10
found a significant differ-
ence in heat pain sensitivity between pre- and postopioid
treatment.
Discussion
This systematic review was conducted to determine and
compare the responsiveness of methods to measure hyperal-
gesia in clinical studies of chronic pain patients on long-term
opioids. Fourteen articles reporting original studies measur-
ing hyperalgesia in those patients were retrieved. Because
clinical OIH has not yet been definitively demonstrated,
it is not possible to directly determine the responsiveness
of measures of this phenomenon. Furthermore, the stud-
ies performed in this area tend to have small sample sizes,
different experimental designs, and different testing proto-
cols, thereby precluding formal meta-analytic methods. The
summary results in table 3 suggest that, on average, none of
the stimuli have sufficient power to detect hyperalgesia in
chronic pain patients on long-term opioids. However, some
specific findings merit attention. For instance, it is notable
that three prospective studies that assessed heat pain ratings
reported heat hyperalgesia when patients were on opioid
therapy (compared with when they were off opioids).5,6,10
Although a larger number of studies have been performed
with ice water immersion, a substantial proportion of these
studies failed to discriminate “known” groups, and the aver-
sive nature of the test should be considered. Mechanical
testing approaches (algometry or von Frey filaments) have
been used several times, never successfully.7,8,11,13,16
Other
approaches (conditioned pain modulation, ischemia, injec-
tion pain) have been unsuccessful, inconsistent, or have been
used too rarely to conclude.7,8,12,14,18
Thus, this review failed to identify a definitive standard
for hyperalgesia measures. This is mainly due to the fact
that the measurements failed to detect a change because the
measures are not sensitive enough, the sample is too small
for the measure to detect change, the studies use subopti-
mal study designs (most being cross-sectional), and/or the
timing of opioid dosing was not controlled for. Moreover,
all these studies provide averages of hyperalgesia variables
over the entire group of opioid-treated patients, which may
obliterate the phenomenon if the development of hyperal-
gesia is a rare occurrence in patients on opioids. Therefore,
clinicians who wish to conduct a clinical trial to measure
hyperalgesia in opioid-treated patients should choose a
randomized controlled trial design and report the propor-
tion of patients on opioids who develop hyperalgesia dur-
ing the treatment. Finally, although most studies focused
on measure responsiveness, assessing reliability and other
forms of validity would also be informative. This review
identified heat stimuli (using the Medoc TSA; Medoc Ltd.
Advanced Medical Systems) as a potentially good candidate
for further testing in future studies. More data should also
be generated with injection pain to determine whether this
method holds true potential.
Importantly, clinicians should be cautious not to take the
increase in pain sensitivity (hyperalgesia) to experimental
stimuli as a proof of OIH in opioid-treated patients. Indeed,
clinical OIH is a syndrome that has three main symptoms:
one of them being an increase in pain sensitivity to external
stimuli and the other two being an increase in pain inten-
sity over time and the spreading of pain to other locations.
To conclude that a patient experiences OIH should rely on
additional evaluation of the patient’s clinical data and medi-
cal history to determine whether all characteristics of clinical
OIH are present. To this end, Chen et al.11
provides a list
of clinical factors that should be taken into account in the
diagnosis of clinical OIH.
Acknowledgments
This study was funded by Campbell Alliance, Raleigh, North
Carolina.
Competing Interests
The authors declare no competing interests.
Correspondence
Address correspondence to Dr. Paillard: Analgesic Solutions,
232 Pond Street, Natick, Massachusetts 01760. fpaillard@
analgesicsolutions.com. This article may be accessed for
personal use at no charge through the Journal Web site,
www.anesthesiology.org.
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