What Fibromyalgia Teaches Us About Chronic Pain

What Fibromyalgia Teaches Us About Chronic Pain

What Fibromyalgia Teaches Us About Chronic Pain

Rethinking the Origin of Chronic Pain
Until relatively recently, most clinicians (and even many pain researchers) considered the majority of chronic pain to be due to ongoing peripheral nociceptive activity (eg, due to damage or inflammation) in peripheral tissues. In a few instances, this lack of concordance between damage/inflammation and pain is well known. For example, nearly all clinicians understand that there is a poor relationship between the results of magnetic resonance imaging or computed tomography scans of the back, and the presence or absence of lumbar pain. However, very few realize that there is not a single chronic pain state where any radiographic, surgical, or pathologic description of peripheral nociceptive damage has been reproducibly shown to reliably identify which individuals will be experiencing pain, or how severe that pain will be. The reason for this appears to be that both the peripheral and central nervous systems (PNS/CNS) play critical roles in determining which nociceptive input detected by sensory nerves in the peripheral tissues will lead to the perception of pain in humans. Many individuals with significant peripheral nociceptive input will not experience pain, and others without any identifiable peripheral nociceptive input will experience severe pain. A central tenet of this review is that within any specific diagnostic category, individual patients may have markedly different peripheral nociceptive and neural contributions to their pain. Thus, just as low back pain has long been acknowledged to have multiple potential mechanisms and thus has sometimes been referred to as a mixed pain state, it is becoming more likely that all chronic pain syndromes may in fact be mixed pain states. This term implies that within each diagnostic category, individuals may have markedly different reasons for their pain. Some individuals will have pain primarily due to peripheral nociceptive input, whereas in others peripheral (eg, peripheral sensitization) or CNS factors (central sensitization, or centralization, of pain via augmented pain processing in the spine and brain) may be playing an equally or even more prominent role in their pain and other symptoms. Making this distinction is critical from a clinical standpoint because both the drug and non-drug therapies that will work for any given chronic pain patient might be much better guided by a nuanced view of the mechanisms of the pain rather than knowing from which of these diagnoses the patient is suffering. This is not a new concept, having first been raised more than a decade ago by Mitchell Max, and later Clifford Woolf and others. However, these authors opined that we should do this in the future; this review suggests that we might finally have made enough scientific progress in the pain field to begin implementing these techniques in clinical practice. img1 Figure 1 briefly describes at least 3 different underlying mechanisms that can be operative in chronic pain states: peripheral nociceptive, peripheral neuropathic, and central neuropathic (or centralized) pain. Some authors use the term neuropathic pain for any pain of neural origin, whereas others reserve this term for conditions where there is identifiable damage to the nervous system. We acknowledge this, but prefer to use the term central (or centralized) pain to refer to the fact that the CNS (rather than the PNS) is prominently involved in maintaining the pain. This distinction between peripheral neuropathic pain (where peripherally directed therapies such as topical treatments, injections, and/or surgery might be helpful, and should be considered) and central neuropathic pain (where these generally are not options) is extremely important. Of note, although specific diagnoses are noted in Figure 1 as being considered peripheral nociceptive, peripheral neuropathic, or central neuropathic (centralized), this is meant to indicate the category in which each of the diagnoses has historically been considered to reside. Again, the emphasis of this review is that some individuals with any chronic pain state have evidence that they have centralized their pain and should likely be treated with centrally acting treatments, whereas other individuals with conditions such as fibromyalgia or irritable bowel syndrome (IBS) may have peripheral contributions to their pain that may need to be identified and treated. Fibromyalgia as the Prototypical Centralized Pain State. The term central pain was originally used to describe individuals who developed pain after a stroke or spinal cord lesion. In this case, central referred to the fact that the lesion leading to pain occurred within the CNS—either spinal cord or brain. More recently, however, the term has expanded to describe any CNS dysfunction or pathology that may be contributing to the development or maintenance of chronic pain. Another term that often has been used to describe this same phenomenon is central sensitization. Using this term can cause some confusion because just like central pain, the original meaning of central sensitization in the pain field referred to a specific spinal cord mechanism that is now realized to be one of many potential causes of augmented CNS pain processing. Central pain, as newly defined, originally was thought to be confined to individuals with idiopathic or functional pain syndromes, such as fibromyalgia, headache, IBS, temporomandibular joint disorder, and interstitial cystitis. These pain syndromes have been shown to be familial/genetic, and to strongly coaggregate in individuals and families. The symptoms experienced by individuals with central pain syndromes have been well characterized and consist of multifocal pain (with a high current and lifetime history of pain in many bodily regions), and a cluster of co-occurring somatic symptoms (ie, fatigue, sleep disturbances, memory difficulties). Even if individuals are identified as having a new onset of a regional pain syndrome, closer questioning often reveals very high rates of pain in other bodily regions, and other somatic symptoms in addition to pain. Screen Shot 2015-12-17 at 3.07.16 PM Using a large Swedish twin registry, Kato and coleagues performed a series of studies first showing the comorbidities with chronic widespread pain. They later examined a number of these central, or functional, pain syndromes and the relationship of symptoms to those of depression and anxiety. These studies clearly demonstrated that functional somatic syndromes such as fibromyalgia, chronic fatigue syndrome, IBS, and headache have latent traits (eg, multifocal pain, fatigue, memory, and sleep difficulties) that are different from (but overlap somewhat with) psychiatric conditions such as anxiety and depression. The notion that there are 2 overlapping sets of traits, one being pain and sensory amplification and the other being mood and affect, also is supported by genetic studies of idio-pathic pain syndromes. Current evidence suggests that genetic factors are approximately 50% responsible for overall sensitivity to experimental pain, and that the same genes that have been identified as increasing sensitivity to experimental pain also make individuals more likely to develop chronic pain over the course of their lifetime. There are at least 5 sets of genes that have been shown to both change an individual’s pain sensitivity and increase their likelihood of developing one or more chronic pain states. These include COMT (an estrogen-sensitive enzyme that may play a more prominent role in females); a number of sodium channel mutations; GTP cyclohydroxylase (GCHI); types 2 and 3 adrenergic receptors; and a potassium channel gene (KCNS). The genes have been most consistently shown to confer a higher risk for pain sensitivity or the development of chronic pain, but not all studies have confirmed these findings. As with most illnesses that may have a familial or genetic underpinning, environmental factors may play a prominent role in triggering the development of fibromyalgia and other central pain states. Environmental stressors temporally associated with the development of either fibromyalgia or chronic fatigue syndrome include early life trauma; physical trauma (especially involving the trunk); certain infections such as hepatitis C, Epstein-Barr virus, parvovirus, and Lyme disease; and emotional stress. The disorder also is associated with other regional pain conditions or autoimmune disorders. Of note, each of these stressors only triggers the development of fibromyalgia and/or chronic fatigue syndrome in approximately 5% to 10% of individuals who are exposed; the overwhelming majority of individuals who experience these same infections or other stressful events regain their baseline state of health. Although fibromyalgia, IBS, and other central pain states were originally felt to be autoimmune or inflammatory diseases (ie, fibrositis, spastic colitis) and then later believed not to be, recent findings are leading to a reconsideration of whether subtle inflammatory or peripheral changes may be responsible for some of the symptoms seen. Furthermore, studies suggest that maintenance of central augmentation requires persistent noxious peripheral input, even in syndromes such as IBS and fibromyalgia, which are characterized by the absence of well-defined, localized, pain-causing lesions. A recent study of 68 patients with fibromylgia and myofascial pain syndromes and 56 patients with fibromyalgia and regional joint pain showed that peripheral trigger-point injections and hydroelectro-phoresis ameliorate fibromyalgia pain and increase pain thresholds at sites distant from the therapeutic interventions, providing further evidence that painful peripheral stimuli contribute to the perpetuation of central augmentation interventions. Role of Central Factors in Classic Peripheral Nociceptive Input Disorders Historically, the “disease” of osteoarthritis (OA) has been viewed primarily as damage to the cartilage and bone. As such, the magnitude of damage or inflammation of these structures should predict symptoms. Population-based studies suggest otherwise; 30% to 50% of individuals with moderate to severe radiographic changes of OA are asymptomatic, and approximately 10% of individuals with moderate to severe knee pain have normal radiographs. Psychological factors do account for some of this variance in pain and other symptoms, but only to a small degree. This failure of peripheral damage, inflammation, or even psychological factors to explain the presence, absence, or severity of chronic pain should not be surprising. To date, no chronic pain state involves a strong relationship between peripheral factors and the level of pain reported.The work done to date supports the hypothesis of OA as a mixed pain state, and in some individuals CNS factors are highly influential. Central factors may be playing a pivotal role in OA, which helps to explain the fact that comorbid somatic symptoms known to be associated with central pain conditions (eg, fatigue, sleep problems) are very commonly present in OA, and are not explained by a purely peripheral model of this disorder. Moreover, both quantitative sensory testing and functional neuroimaging studies suggest that patients with OA display diffuse hyperalgesia to mechanical or heat stimuli, some of which normalizes following hip arthroplasty. This further suggests that the central factors were being at least partly driven by peripheral nociceptive input. Finally, recent randomized controlled trials have demonstrated that compounds that alter pain neurotransmitters centrally such as serotonin and norepinephrine (eg, duloxetine [Cymbalta, Lilly], milnacipran [Savella, Forest], tricy-clics) are efficacious in OA. Screen Shot 2015-12-17 at 3.07.16 PM Basing Pharmacologic Therapy on Underlying Mechanism(s) of Pain Figure 2 shows the classes of drugs that seem most effective in different underlying mechanisms of pain. For peripheral nociceptive, noninflammatory pain states such as OA, treatment guidelines typically recommend first using acetaminophen, and then non steroidal anti-inflammatory drugs (NSAIDs). It is now generally thought that acetaminophen is safer, but less effective, than NSAIDs. Although opioids previously had been considered to be very useful for pain refractory to these treatments, the latest meta-analyses of opioids in OA challenge this notion, and generally recommend against opioid use. Although older studies supported the fact that tricyclic compounds may be effective in OA, these drugs have significant toxicity, especially in the elderly. Because of this, newer drugs that also are likely working by increasing serotonergic and noradrenergic activity, such as tramadol and duloxetine, are more commonly used. Although many in the pain field strongly suspect that these latter centrally acting analgesics (this term is used cautiously because most analgesics have potential peripheral and central mechanisms) will be more effective in individuals with peripheral nociceptive pain that has centralized to date, there have been no studies that have definitively proved this. In inflammatory, peripheral pain states such as rheumatoid arthritis, a whole host of anti-inflammatory or disease-modifying drugs also are used in addition  to the above drugs. It is likely that these drugs both directly decrease pain by reducing inflammation, and also reduce peripheral sensitization that may occur due to ongoing inflammation. The classes of drugs that preferentially work for neuropathic or centralized pain states again include the serotonin-norepinephrine reuptake inhibitors (eg, tricyclics, tramadol, duloxetine) as well as the calcium channel ligands (pregabalin [Lyrica, Pfizer] and gabapentin).Peripheral pain syndromes (including both inflammatory and noninflammatory peripheral pain, and peripheral neuropathic pain) also can be treated with topical agents or injections. Injections of corticosteroids, hyaluronic acid preparations (for OA in joints that can be injected), agents that ablate nerves, or capsa-icin (effective in both OA and neuropathic pain) are all therapeutic options. References 1.    Boden SD, McCowin PR, Davis DO, et al. Abnormal magnetic-resonance scans of the cervical spine in asymptomatic subjects. A prospective investigation. J Bone Joint Surg Am. 1990;72(8):1178-1184. 2.   Max MB. Is mechanism-based pain treatment attainable? Clinical trial issues. J Pain. 2000;1(3 suppl):2-9. 3.   Woolf CJ. Pain: moving from symptom control toward mechanism-specific pharmacologic management Ann Intern Med. 2004;140(6):441-451. 4.   Woolf CJ, Thompson SW. The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states. Pain. 1991;44(3):293-299. 5.   Clauw DJ, Schmidt M, Radulovic D, et al. The relationship between fibromyalgia and interstitial cystitis. J  Psychiatric Res. 1997;31(1):125-131. 6.   Hudson JI, Pope HG. The concept of affective spectrum disorder: relationship to fibromyalgia and other syndromes of chronic fatigue and chronic muscle pain. Baillieres Clin Rheumatol. 1994;8(4):839-856. 7.   Diatchenko L, Nackley AG, Slade GD, et al. Idiopathic pain disorders—path ways of vulnerability. Pain. 2006;123(3):226-230. 8.   Williams DA, Clauw DJ. Understanding fibromyalgia:  lessons from the broader pain research community. J Pain. 2009;10(8):777-791. 9.   Warren JW, Howard FM, Cross RK, et al. Antecedent nonbladder syndromes in case-control study of interstitial cystitis/painful bladder syndrome. Urology . 2009;73(1):52-57. 10. Kato K, Sullivan PF, Evengard B, et al. A population-based  twin study of functional somatic syndromes.Psychol Med. 2009;39(3):497-505 .
Researchers have discovered the recipe for painlessness

Researchers have discovered the recipe for painlessness

People born with a rare genetic mutation are unable to feel pain, but previous attempts to recreate this effect with drugs have had surprisingly little success. Using mice modified to carry the same mutation, UCL researchers funded by the MRC and Wellcome Trust have now discovered the recipe for painlessness.

‘Channels’ that allow messages to pass along nerve cell membranes are vital for electrical signalling in the nervous system. In 2006, it was shown that sodium channel Nav1.7 is particularly important for signalling in pain pathways and people born with non-functioning Nav1.7 do not feel pain. Drugs that block Nav1.7 have since been developed but they had disappointingly weak effects.

The new study, published in Nature Communications, reveals that mice and people who lack Nav1.7 also produce higher than normal levels of natural opioid peptides.

To examine if opioids were important for painlessness, the researchers gave naloxone, an opioid blocker, to mice lacking Nav1.7 and found that they became able to feel pain. They then gave naloxone to a 39-year-old woman with the rare mutation and she felt pain for the first time in her life.

“After a decade of rather disappointing drug trials, we now have confirmation that Nav1.7 really is a key element in human pain,” says senior author Professor John Wood (UCL Medicine). “The secret ingredient turned out to be good old-fashioned opioid peptides, and we have now filed a patent for combining low dose opioids with Nav1.7 blockers. This should replicate the painlessness experienced by people with rare mutations, and we have already successfully tested this approach in unmodified mice.”

Broad-spectrum sodium channel blockers are used as local anaesthetics, but they are not suitable for long-term pain management as they cause complete numbness and can have serious side-effects over time. By contrast, people born without working Nav1.7 still feel non-painful touch normally and the only known side-effect is the inability to smell.

Opioid painkillers such as morphine are highly effective at reducing pain, but long-term use can lead to dependence and tolerance. As the body becomes used to the drug it becomes less effective so higher doses are needed for the same effect, side effects become more severe, and eventually it stops working altogether.

“Used in combination with Nav1.7 blockers, the dose of opioid needed to prevent pain is very low,” explains Professor Wood. “People with non-functioning Nav1.7 produce low levels of opioids throughout their lives without developing tolerance or experiencing unpleasant side-effects. We hope to see our approach tested in human trials by 2017 and we can then start looking into drug combinations to help the millions of chronic pain patients around the world.”

The findings were made possible by the use of ‘transgenic’ mice, meaning they were modified to carry genetic material from another organism — in this case, the mutation that prevents humans from feeling pain. Precise physiological experiments showed that the nervous systems of the transgenic mice contained around twice the levels of naturally-produced opioids as unmodified mice from the same litter.

“Our results reaffirm the clinical relevance of transgenic mouse models for human diseases,” says Professor Wood. “Studying the mice showed us what was going on in the nervous system that led to painlessness and our findings were directly translatable to humans, as confirmed by the painless patient. Without the work in transgenic mice, none of this would have been possible and we still wouldn’t know how to replicate the effects to help people suffering from chronic pain.”

Story Source:

University College London. “Genetically modified mice reveal the secret to a painless life: Researchers have discovered the pharmaceutical recipe for painlessness.” ScienceDaily. ScienceDaily, 4 December 2015. <www.sciencedaily.com/releases/2015/12/151204090034.htm>

Journal Reference:

  1. Michael S. Minett, Vanessa Pereira, Shafaq Sikandar, Ayako Matsuyama, Stéphane Lolignier, Alexandros H. Kanellopoulos, Flavia Mancini, Gian D. Iannetti, Yury D. Bogdanov, Sonia Santana-Varela, Queensta Millet, Giorgios Baskozos, Raymond MacAllister, James J. Cox, Jing Zhao, John N. Wood. Endogenous opioids contribute to insensitivity to pain in humans and mice lacking sodium channel Nav1.7Nature Communications, 2015; 6: 8967 DOI: 10.1038/ncomms9967


Latest Pain Research News

Latest Pain Research News

Scientific breakthroughs happen every day!  In an effort to help our patients stay up to speed on the most cutting edge treatment options available for them, our scientists monitor current research and publish weekly research updates.  The title of each article below is a link to the full study report.  If you’d like to make an appointment with Dr. Hanna to discuss your treatment options, please contact us.


Innate immunity of surfactant proteins A and D in urinary tract infection with uropathogenic Escherichia coli

F Hu, G Ding, Z Zhang, LA Gatto, S Hawgood… – Innate Immunity, 2015

UTI was induced as previously described, 30 with some modifications. In brief, mice were

anesthetized by ip injection with ketamine/xylazine (90 mg/kg ketamine and 10 mg/kg xylazine),

and were gently massaged and pushed down on the bladder to expel urine.

[PDF] Comparison of propofol and ketofol in minor gynecologic interventions

Y Işık, Z Kurdoğlu, U Göktaş, İ Katı, D Sözen – J Clin Exp Invest www. jceionline. org …, 2015

Propofol is administered as an infusion instead of in repeated doses, which prevents

dose-dependent respiratory and cardiovascular system depression and pro- vides controlled

sedation [1]. Ketamine is preferred for premedication, anesthesia induction and main- tenance

Anesthesia Complications of Pediatric Radiotherapy

V Verma, AB Beethe, M LeRiger, RR Kulkarni, M Zhang… – Practical Radiation …, 2015

While agents such as ketamine (complication rates approaching 23-24%) have been used

in the past, other agents such as propofol and volatile anesthetics have lower complication

rates due to improved drug side effect profiles (0.01-3.5%).

[HTML] Stress activates the nucleus incertus and modulates plasticity in the hippocampo-medial prefrontal cortical pathway

R Rajkumar, Y Wu, U Farooq, WH Tan, GS Dawe – Brain Research Bulletin, 2015

Ketamine (Parnell Manufacturing Pty Ltd; Alexandria, NSW, Australia), xylazine (Ilium Xylazil,

Troy Laboratories Pty Ltd; Glendenning, NSW, Australia), enrofloxacin (Baytril 5%, Bayer Health

Care; Seoul, Korea) and carprofen (Carprieve, Norbrook Laboratories (GB), Ltd

The role of glutamatergic, GABA-ergic, and cholinergic receptors in depression and antidepressant-like effect

K Pytka, A Dziubina, K Młyniec, A Dziedziczak… – Pharmacological Reports, 2015

Depression is one of the most common mental disorders and social issue worldwide. Although

there are many antidepressants available, the effectiveness of the th.

[HTML] Communicating with mismatch and tension: treatment provision experiences of primary care doctors treating patients with overactive bladder in Hong Kong

JY Siu – BMC Family Practice, 2015

[P6]. During the study period, the symptoms of OAB, particularly urinary frequency and

urinary incontinence, were identified by government antisubstance abuse public service

announcements as signs and consequences of ketamine abuse.

Hydrogen sulfide (H 2 S) attenuates uranium-induced acute nephrotoxicity through oxidative stress and inflammatory response via Nrf2-NF-κB pathways

J Zheng, T Zhao, Y Yuan, N Hu, X Tang – Chemico-Biological Interactions, 2015

sacrificed. After urine collection, rats were anesthetized by an ip injection of

ketamine-xylazine (50 mg/kg ketamine and 5 mg/kg xylazine), and blood samples

were obtained directly from the heart ventricle in anesthetized animals.

[PDF] General discussion and future perspectives

SA Bouwense, M de Vries, LT Schreuder, SS Olesen… – PDF hosted at the Radboud …, 2015

even if technically successful. If central nervous system pain processing is altered,

specific treatment targeting these changes should be instituted (eg gabapentinoids,

ketamine or tricyclic antidepressants). Suitable tools are

Propofol target-controlled infusion for sedated gastrointestinal endoscopy: A comparison of propofol alone versus propofol–fentanyl–midazolam

CD Hsu, JM Huang, YP Chuang, HY Wei, YC Su… – The Kaohsiung Journal of …, 2015

The currently used regimens include propofol, benzodiazepines (such as midazolam and

diazepam), opioids (such as fentanyl and remifentanil), ketamine, and de-dexmedetomidine

[3], [4], [5] and [6]. Among them propofol has become popular in developed countries, because

[PDF] A Critical Case of Closed Cervix Pyometra in a Bitch

JK Agrawal, A Saxena, P Kumar, A Patel – International Journal of Livestock Research, 2015

General anethesia was induced and maintained by a combination of ketamine hydrochloride @

5mg/kg and Xylazine @ 0.2mg/kg body weight intravenously following premedication with atropine

sulphate @ 0.04mg/kg body weight. Laparotomy was performed

Radiofrequency Ablation (RFA)

Treatment of Neuroendocrine Liver Metastases

HA Farley, RF Pommier – Surgical Oncology Clinics of North America, 2015

Treatment options: radiofrequency ablation. RFA is another technique used to treat

neuroendocrine metastases of the liver, but it has limitations. One can ablate a limited number

of lesions (generally up to 5), of limited size (generally <5 cm in diameter), provided they are

[PDF] Ablative Techniques in Advanced Pancreatic Cancer: Do They Affect The Quality of Life?–Review

D Dimitrov, H Feradova, D Gincheva, L Dall’Olio – JOP. J Pancreas (Online), 2015

Such ablative therapies are high-intensity focused ultrasound (HIFU), radiofrequency

ablation (RFA), irreversible electroporation (IRE), iodine-125, iodine-125–cryosurgery,

photodynamic therapy (PDT) and microwave ablation [8].

Minimally Invasive Techniques for Resection of Pancreatic Neuroendocrine Tumors

GGF Ranvier, D Shouhed, WB Inabnet – Surgical Oncology Clinics of North America, 2015

Please note that Internet Explorer version 8.x will not be supported as of January 1,

2016. Please refer to this blog post for more information. Close.

[HTML] Colorectal Liver Metastasis, Primary Gallbladder Carcinoma and Myelofibrosis Present Simultaneously in a Liver Resection Specimen

SA Gray, MH Raber, E Provoost, GJ Toes, JM Klaase – Case Reports in …, 2015

An elective operation was scheduled, and the surgeon performed a wedge resection of segments

5 and 7 of the liver, and a radiofrequency ablation was used to treat a lesion in segment 3.

Although the suspicion of gallbladder carcinoma at the time of surgery was low, the

Nontraumatic Cervical Spine for Primary Care Providers

CR Hemmer – The Journal for Nurse Practitioners, 2015

physical therapy, a home traction unit, transcutaneous electrical nerve stimulation, epidural steroid

injections, selective nerve root blocks (transforaminal injections), botulinum toxin type A injections,

medication management, radiofrequency ablation, and surgical correction.

Surgical Management of Adrenocortical Carcinoma: An Evidence-Based Approach

J Datta, RE Roses – Surgical Oncology Clinics of North America, 2015

Please note that Internet Explorer version 8.x will not be supported as of January 1,

2016. Please refer to this blog post for more information. Close.


S Narayan, R Sehra – US Patent 20,150,289,807, 2015

For instance, ablation success for atrial tachycardias (a ‘simple’ disorder) may be as low as 70%.

Thus, ablating the cause of a heart rhythm disorder can be challenging, and even experienced

practitioners may require hours to ablate certain ‘simple’ rhythm disorders


S Navalkissoor, G Gnanasegaran – Journal of Cancer & Allied Specialties, 2015

These include surgical debulking, chemotherapy, molecular targeted therapies (eg sunitinib

and everolimus), interferon, somatostatin analogues, local therapies (eg radiofrequency ablation

or embolisation) and peptide receptor radionuclide therapy (PRRT).

[PDF] Successful Radiofrequency Pulmonary Vein Isolation In A Patient With Pneumonectomy

F Kilicaslan, EE Gul, C Erol

Circumferential radiofrequency ablation of ipsilateral PVs was done (30-35 W, 17

mL/min) with irrigated catheter (Sprinklr, Medtronic, Minneapolis, USA) and both,

entrance and exit blocks were achieved after the ablation. Interestingly

[PDF] Ablation Is A Treatment Option Without Permanent Pacemaker Implantation For Bradycardia With Persistent Atrial Fibrillation

W Yamada, K Tanimoto, M Yamada, K Inagawa…

Page 5. Rotational Atriography Of Left Atrium – A Imaging Technique Used To Support Left Atrial

Radiofrequency Ablation: A Comparison Of Anatomical Data Of Left Atrium F. Lehar, Z. Starek,

J. Jez, J. Wolf, T. Kulik, A. Zbankova, M. Novak Department of Cardiology, ICRC/St.

Complex Regional Pain Syndrome (CRPS/RSD)

[PDF] Do insiders trade on mispricing after earnings announcements?

JP Fidrmuc, J Novák, H Contreras – 2015

Page 1. Do insiders trade on mispricing after earnings announcements? Jana P.

Fidrmuc∗ Warwick Business School Jirı Novák† Charles University Harold Contreras‡

Warwick Business School October 21, 2015 Abstract This

[PDF] A predictive framework for evaluating models of semantic organization in free recall

NW Morton, SM Polyn – Journal of Memory and Language, 2015

Research in free recall has demonstrated that semantic associations reliably influence the

organization of search through episodic memory. However, the specific.


GW Muller, H Man – US Patent 20,150,291,555, 2015

Examples of diseases or disorders include, but are not limited to, cancer, disorders associated

with angiogenesis, pain including, but not limited to, Complex Regional Pain Syndrome (“CRPS”),

Macular Degeneration (“MD”) and related syndromes, skin diseases, pulmonary

[PDF] Psychological distress and stressful life events in pediatric complex regional pain syndrome

MD Hannah Brehmer, MD Boris Zernikow

Complex regional pain syndrome (CRPS) is increasingly recog- nized as a serious pain

disorder in children and adolescents. Specifically, it is not known which factors precipitate

CRPS and which result from the ongoing painful disease.

[PDF] In the High Court of New Zealand Wellington Registry


Pain News 11 (1) 2013 pages 30-33. Safarfashandi Z, Munglani R, Safarfashandi L, Sadheura

J, Jenner C “The incidence of complex regional pain syndrome (CRPS) post trauma and the

possible role of tight plaster of Paris in the aetiology of CRPS“.

[PDF] Assessment Report

CO Onyango, Y Suwa, Y Pinto

directory ….. 18 – Table 5: List of ASTI publications in Phase II 3 ….. 20 Table 6: Summary of

ex-post impact assessments by CGIAR Centres, CRPs and SPIA ….. 29

[PDF] Hereditary Immunity against Infectious Diseases

IA Shabarov, ZI Urmancheeva, SN Rumyantsev…

Page 1. 1 Innovative Immunology | www.austinpublishinggroup.com/ebooks Copyright

© Rumyantsev SN.This book chapter is open access distributed under the Creative

Commons Attribu- tion 4.0 International License, which

Encyclopedia of Exploration Geophysics

M this Chapter

Page 1. U1-1 Abstract To produce a reliable image of the subsur- face, we must use

a depth-migration scheme that requires a detailed model of the parameter fields for

use by migration. Obtaining reliable values of all parameters


[PDF] Does “Multiple Labeling” Benefit or Harm in Fibromyalgia Patients

E Trallero, C Alegre – Fibrom open, 2015

A systematic review showed that there is no evidence an accurate diagnosis of fibromyalgia 

per se could worsen prognosis in patients with this condition [1]. Indeed, it could be useful to 

reduce healthcare utilization by patients. Nevertheless, social and individual long-term

[PDF] Comparison between Depression Levels of Women with Knee Osteoarthritis, Rheumatoid Arthritis, and Fibromyalgia Syndrome: A Controlled Study

D Karşılaştırılması, BK Çalışma – 2015

DOI: 10.5152/tftrd.2015.87894 Turk J Phys Med Rehab 2015;61:197-202 Türk Fiz Tıp Rehab 

Derg 2015;61:197-202 Comparison between Depression Levels of Women with Diz 

Osteoartrit, Romatoid Artrit ve Fibromiyalji Sendromlu Kadınlarda Depresyon


CH Lee, K Lee – US Patent 20,150,291,509, 2015

group consisting of dermatitis, allergy, atopy, conjunctivitis, periodontitis, rhinitis, tympanitis,

pharyngolaryngitis, tonsillitis, pneumonia, gastric ulcer, gastritis, Crohn’s disease, colitis, irritable

colitis, hemorrhoids, gout, ankylosing spondylitis, lupus, fibromyalgia, psoriasis, arthritis

[PDF] Recent advances in massage therapy–a review

SL LIU, W Qi, H Li, YF WANG, XF YANG, ZM LI, Q Lu… – Eur Rev Med Pharmacol Sci, 2015

in animal models. In a randomized trial conducted by Ekici et al13, application of

MLD to women with fibromyalgia resulted in improvements regarding pain, health

status, and health-related quality of life. Lancaster and Crow14

Immediate Effect of Basic Body Awareness Therapy on Heart Rate Variability

AM Mantovani, CEPT Fregonesi, RMR Lorençoni… – … Therapies in Clinical …, 2015

To determine the immediate effect of a Basic Body Awareness Therapy (BAT) session on

measures of heart rate variability (HRV) in healthy young people.13 healthy.

[PDF] Radial shock wave therapy in the treatment of lateral epicondylitis

JD Rompe, J Decking, C Schoellner, C Theis…

P009-e Gait analysis: An objective measurement for subgrouping fibromyalgia patients B. Auvinet

a,*, D. Chaleil b, J. Cabane c, A. Dumolard d, P. Hatron e, R. Juvin d, M. Lanteri-minet f, Y. Mainguy

g, L. Negre-pages h, F. Pillard i, D. Riviere i, Y. Maugars j a Clinique, 8, rue des


D Brunner, J Malberg, BG Shankar, S Kolczewski… – US Patent 20,150,284,386, 2015

Fibromyalgia, which is a syndrome characterized by chronic generalized pain associated with

different somatic symptoms, such as sleep disturbances, fatigue, stiffness, balance problems,

hypersensitivity to physical and psychological environmental stimuli, depression and


JE Campbell, P Jones – US Patent 20,150,291,626, 2015

affective disorder, seasonal affective disorder, obsessive-compulsive disorder, attention deficit

disorder, attention deficit hyperactivity disorder, vertigo, pain, neuropathic pain, sensitization

accompanying neuropathic pain, inflammatory pain, fibromyalgia, migraine, cognitive

[PDF] How is Qigong Conducive to Women’s Health

FK Cheng – Int J Complement Alt Med, 2015

Likewise, Tai Chi is beneficial for treating fibromyalgia, achieving better symptomatology,

aerobic capacity, dynamic balance, body strength, and walking distance [112]. Psychological

health: Studies inform the effects of Baduanjin on mental well-being.

[HTML] Recommendations to the primary care practitioners and the patients for managing pelvic pain, especially in painful bladder syndrome for early and better prognosis

KJ Chung, ANY Han, KH Kim – Journal of Exercise Rehabilitation, 2015

Scholar]. Nickel JC., Tripp DA., Pontari M., Moldwin R., Mayer R., Carr LK., Doggweiler R., Yang

CC., Mishra N., Nordling J. Interstitial cystitis/painful bladder syndrome and associated medical

conditions with an emphasis on irritable bowel syndrome, fibromyalgia and chronic


New research reveals that greater frequency and duration of daytime napping are associated with more severe symptomatology in patients with fibromyalgia.

New research reveals that greater frequency and duration of daytime napping are associated with more severe symptomatology in patients with fibromyalgia.

New research reveals that greater frequency and duration of daytime napping are associated with more severe symptomatology in patients with fibromyalgia.


According to the study results, published in BMC Musculoskeletal Disorders (2015 Feb 7;16:13. doi: 10.1186/ s12891-015-0464-y), the majority of participants reported using daytime napping as a strategy for coping with poor sleep and fibromyalgia symptoms. “Participants who regularly took a daytime nap were found to have a higher number of comorbidities, increased levels of pain, fatigue, sleep problems, memory difficulties and mood disturbance in comparison to participants with fibromyalgia who napped less regularly or not at all,” reported Alice Theadom, PhD, senior research fellow at the National Institute for Stroke and Applied Neurosciences, in Auckland, New Zealand.

Whereas previous research has shown sleep to be problematic for people with fibromyalgia, uncertainty remains over whether daytime napping is a beneficial or detrimental coping strategy.

“We found that poor sleep has been linked to poorer outcomes, and we found associations between difficulty falling asleep or waking up during the night with greater levels of pain and fatigue and other symptoms in this condition,” Dr. Theadom stated. “What we were looking at specifically in this study, however, was the impact of how people use daytime naps as a way of managing feelings of fatigue or tiredness during the day.”

An online questionnaire of 1,044 adults who reported napping on a daily basis showed that 18.9% napped in the morning of a typical weekday, 58.8% napped in the afternoon and 25% napped in the evening. It was also revealed that 86.5% of participants found themselves taking a nap without intending to, Dr. Theadom reported.

“Daytime napping was significantly associated with higher levels of pain, feelings of low mood and anxiety, and people feeling more fatigued, as well as memory difficulties and difficulty sleeping at night,” she said. “So daytime napping seemed to be linked to quite a range of symptoms.”

Daytime napping was also associated with a high rate of comorbid conditions, including arthritis (20%), irritable bowel syndrome (15%) and asthma (13%). Of those surveyed, 5.1% reported a psychiatric condition and 11.2% had depression, Dr. Theadom said. Finally, the duration of naps was found to have an influence on the impact of symptoms.
Those who engaged in daytime naps for longer than 30 minutes had greater memory difficulties and levels of depression than those who napped for shorter periods (P<0.010).

The most common reasons for taking a nap included tiredness/exhaustion (94.1%), feeling unwell (67.2%), catching up from the previous night’s poor sleep (59.6%), headache (42.6%) and pain (26.2%).

Although studies of people unaffected by a medical condition have shown a direct correlation between duration of napping and performance outcomes, Dr. Theadom stressed that the data for those with fibromyalgia remain inconclusive. Further research is needed, she said, to understand whether daytime napping is detrimental to symptom severity or whether it can be recommended as a strategy to manage symptoms.

“It’s really important that we try to unpick this so we can make fruitful recommendations to patients who are experiencing difficulties in fatigue,” Dr. Theadom concluded. “We need to provide guidelines so that patients know whether to use the daytime nap or not, and if so, for how long and when.”

“Fibromyalgia is a disorder not only about pain,” said Stuart Silverman, MD, FACP, FACR, former medical director and founder of the multidisciplinary outpatient Fibromyalgia and Chronic Pain Program at Cedars-Sinai in Los Angeles, “but about fatigue, sleep, cognitive dysfunction and also irritable bowel and irritable bladder. People who have more severe fibromyalgia, in terms of decreased functioning, also have more pain, more fatigue, more cognitive problems and more sleep disorders. This study is reinforcing our concept of fibromyalgia as a multisymptom illness. It is more than pain.”
—Chase Doyle

Ketamine May Reduce Chronic Pain in Adolescents

Ketamine May Reduce Chronic Pain in Adolescents

Ketamine May Reduce Chronic Pain in Adolescents


Subanesthetic ketamine infusions are a safe and effective way to relieve chronic pain in adolescents, a new study suggests.

Ketamine, a Schedule III drug, has been used successfully to treat various chronic pain syndromes in adults, according to researchers from Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National Health System, in Washington, D.C., who conducted a longitudinal case series to determine the feasibility of ketamine injections in an outpatient setting.

“Our purpose was to look at the clinical outcomes related to our adolescents who were receiving what we considered subanesthetic dosing of ketamine,” said study author Kathy Ann Sheehy, CNS, a nurse specialist at the hospital.

The study included 63 adolescents with chronic pain conditions such as complex regional pain syndrome (CRPS), fibromyalgia and headache, and were treated in the hospital’s tertiary outpatient interdisciplinary Pain Medicine Care Complex from January 2013 to April 2014. The patients received 111 treatments (277 ketamine infusions; maximum dose of 1 mg/kg per hour) during the study period. They were divided into two groups: CRPS (n=23) and all other chronic pain syndromes (n=40). Main outcome measures were self-reported pain scores using a numeric rating scale and morphine-equivalent intake.

The researchers found that ketamine significantly decreased pain scores in 37% of the injections administered. A reduction of 20% or greater was considered significant. Patients with CRPS experienced the greatest reduction compared with the other chronic pain syndromes (P=0.029). The researchers noted that the ketamine infusions did not change the overall morphine-equivalent intake (P=0.3).

“When we looked at the difference between the types of pain syndromes, CRPS was the one that was the most statistically significant as a pain syndrome for reduction in pain scores and reduction in opioid use,” Ms. Sheehy said. “[With] the other pain scores, although overall there was a reduction, we didn’t see a reduction in headaches or other types of complex pain syndromes.”

An analysis of comorbidities showed that:

  • 23% of the patients had psychiatric/psychological disorders (e.g., anxiety, depression, bipolar disorder);
  • 10% had a history of trauma;
  • 10% had postural orthostatic tachycardia syndrome (POTS);
  • 7% had diabetes mellitus;
  • 7% had a malignancy; and
  • 5% had sickle cell disease.

The researchers found that the patients with POTS and trauma experienced the greatest pain reduction and chronic headache patients had the smallest decrease. “Our assumption for that is that both of those are autonomic sympathetic conditions, and most of our CRPS kids actually had trauma,” Ms. Sheehy said.

No adverse events were reported and the ketamine injections were well tolerated, according to the study authors. They said more research on complex pain syndromes, especially CRPS in adolescents, is needed.