Questions for Your Doctor: Fibromyalgia

Questions for Your Doctor: Fibromyalgia

Questions for Your Doctor: Fibromyalgia
image001Between aching muscles, tender skin, fatigue, headaches, flulike symptoms and difficulties concentrating, you may wonder if you’re a hypochondriac. You could have fibromyalgia. Start by asking your doctor these 15 questions about symptoms of fibromyalgia

One day you have aching muscles, tender skin, fatigue, headaches, flulike symptoms and difficulties concentrating. The next day you feel great.

That’s one reason coping with fibromyalgia symptoms is such a challenge.

But a doctor-approved treatment plan — which may include exercise, psychotherapy, medication and natural remedies — can help.

Here are 15 important questions to ask about your symptoms of  fibromyalgia and treatment:

1. Could there be another cause for my symptoms?
Before making a fibromyalgia diagnosis, doctors typically rule out other conditions that cause similar symptoms, such as thyroid disease, arthritis, lupus, infections and some medications (like those used to treat high cholesterol).

Unfortunately, there’s no objective measure — like an X-ray or a blood test — to decisively diagnose fibromyalgia.

2. What’s my long-term outlook?
Early diagnosis of the symptoms of fibromyalgia and treatment is the key to successfully managing symptoms of fibromyalgia, says Leslie Crofford, M.D., chief of rheumatology and director of the Center for the Advancement of Women’s Health at the University of Kentucky in Lexington.

“If you catch it early and develop a good self-management strategy, the condition doesn’t have to dominate your life,” she says.

3. What’s the first-line treatment for symptoms of fibromyalgia?
Your doctor may prescribe one of the following medications, which treat fibromyalgia in two different ways:

  • Duloxetine (Cymbalta) and milnacipran (Savella) increase the amount of two neurotransmitters, serotonin and norepinephrine, in the brain. This reduces your sensitivity to pain.
  • Pregabalin (Lyrica) blocks overactivity of nerve cells, which also reduces pain.

About half of those who try these drugs see modest improvement, Dr. Crofford says. Some patients respond better to medication than others.

“There may be other pathways involved in pain for which neither of these medications work well,” she says.

4. If these medications don’t help, what’s the next step?

IV Ketamine Infusion therapy has been shown to be very effective in treating Fibromyalgia

Your doctor may prescribe older medications “off-label.”

Although the Food and Drug Administration (FDA) hasn’t approved them for fibromyalgia, it allows physicians to prescribe such drugs to treat the condition.

These include amitriptyline (Elavil), cyclobenzaprine (Flexeril) and venlafaxine (Effexor), which increase neurotransmitters in the brain.

Also, antidepressants that affect only one neurotransmitter — such as fluoxetine (Prozac), paroxetine (Paxil) and sertraline (Zoloft) — are sometimes prescribed.

Another older drug, gabapentin (Neurontin), blocks overactivity of nerve cells.

5. Since many drugs used to treat fibromyalgia are antidepressants, is the disease psychological?
No. With fibromyalgia, the cause is a chemical change in the way the central nervous system (the brain and spinal cord) responds to pain, says Daniel Clauw, M.D., a rheumatology professor at the University of Michigan in Ann Arbor.

6. How do antidepressants ease my symptoms of fibromyalgia?
Some antidepressants have other effects too, Dr. Crofford says. The neurotransmitters they increase — serotonin and norepinephrine — also influence the way the brain responds to pain.

7. Are there medications to avoid?
People with fibromyalgia shouldn’t take opioids, including prescription pain medicines, such as Vicodin (acetaminophen and hydrocodone) and Oxycontin (oxycodone), she says.

“These medications actually contribute to the persistence of chronic pain,” she says. “They change the way your brain and spinal cord processes pain. When you stop them, there’s a rebound effect.”

This means your symptoms may actually worsen after you stop taking the drugs.

8. Will I need to make lifestyle changes?
Yes. Patients with the best results combine drug and non-drug therapies, Dr. Clauw says.

“You can’t just rely on pills,” Dr. Crofford adds.

For example, exercise is as important as medication. Inactivity disrupts the body’s natural rhythms and causes sleep problems, says Crofford. It actually leads to fatigue as well as deconditioning (muscle weakness), making daily activities more likely to cause injury and pain.

Overall, “staying in bed is one of the worst things you can do,” she says.

9. How can I exercise when it’s so hard to get up and move?
If your symptoms make exercise difficult, start off slowly, Dr. Crofford advises. Then begin to build endurance.

Find an activity you can do year-round.

If you’ve been inactive for a while, it can be as simple as taking the stairs instead of an elevator, Dr. Clauw says.

“If you haven’t had success in the past, try warm-water aerobics,” he suggests. This puts less stress on muscles and joints.

10. Is it possible to do too much?
Yes. Learn to pace your activities so you don’t overdo it on days you feel well, Dr. Crofford says. You’ll figure that out through trial and error.

11. How can I minimize a flare-up?
Think about what could have caused it. What was I doing the day before? Did I do too much? Or did I not move enough? Did something stressful happen?

Once you begin to see a pattern, avoid situations that cause you discomfort.But try not to dwell on it.

“With fibromyalgia, you may feel widespread pain followed by no symptoms at all,” Dr. Crofford says.

Focusing on symptoms always increases their severity.

Brooding about your condition can lead to depression too, she adds.

12. Other than exercise and medication, what else can reduce pain?
Don’t smoke. Exercise, get enough sleep, and eat a nutritious diet (including plenty of whole grains, fruits and vegetables).

These will keep your body strong and help you cope when symptoms of fibromyalgia flare, she advises.

Also, cognitive behavioral therapy (CBT) can teach you strategies to improve sleep, reduce stress and pace activities.

For basic, do-it-yourself CBT techniques, visit the Fibromyalgia Network website.

13. Will alternative therapies, such as massage, acupuncture, tai chi or yoga, help?
Some randomized trials show that yoga and tai chi help, Dr. Crofford says.

A 2010 study published in the New England Journal of Medicine studied 66 people with symptoms of fibromyalgia.

Half did stretching exercise, and the others practiced tai chi, which includes slow breathing, exercise and meditation — components thought to have physical, social and psychological effects.

The tai chi group showed significant improvement in their symptoms as well as sleep quality, mood and quality of life.

Although there’s no scientific evidence to back up other therapies like massage and acupuncture, some fibromyalgia sufferers claim they provide relief.

But you may actually have to try them before deciding if they work for you, Dr. Crofford adds.

14. What about supplements?
According to the National Center for Complementary and Alternative Medicine (NCCAM) it’s possible that low magnesium levels play a role in fibromyalgia, but there’s no conclusive evidence and more research is needed, Dr. Clauw says.

Still, he recommends magnesium to his patients because “it helps with the constipation associated with many fibromyalgia medications.”

15. How can I explain my disorder to friends and family?
“Bring your family to a doctor’s appointment,” Dr. Clauw says.

“The more educated they are, the better they can advocate for you.”

Symptoms of fibromyalgia are generally invisible to others, so “don’t get too caught up in trying to prove to people that you’re sick,” he advises.

Make sure family members are informed and supportive.

It will help when you need coaching.

“A fibromyalgia patient in the midst of a flare doesn’t want to exercise,” he says.

That’s when you need “gentle, nonjudgmental persuasion to get out of bed and go for a walk.”

By Ellen Wlody

Treating Chronic Pain With Ketamine

Treating Chronic Pain With Ketamine

Treating Chronic Pain With Ketamine


By Christine Lin, Epoch Times

NEW YORK—As human beings, we instinctively avoid pain—the sting of nettles, the burn of a hotplate, the pinching of door hinges. Pain is useful because it communicates immediate danger and helps us keep out of it. However, some pain is chronic, as neuropathic pain often is.Neuropathic pain derives from the central nervous system or peripheral nervous system. It is pain that comes from the nerves, as opposed to common muscular aches and arthritic pain. Sometimes it is triggered by traumatic accidents.

In support forums, patients suffering from neuropathic pain describe their symptoms as “burning all over,” “shooting pains in the arms and legs,” “agony,” and “unbearable.” Many of them recount their experiences in seeking relief “frustrating,” that they’ve “tried everything,” or that “not one doctor can give me an answer.”

Neuropathic pain, as a broad category of conditions that include neuralgia, phantom limb syndrome, complex regional pain syndrome (CRPS), and central pain syndrome, is a little-understood realm in medicine. We don’t always know its causes. And current treatment methods are mediocre at best.

Even its occurrence rate among the general population is hard to discern.

In 2008, a study of neuropathic pain incidences in the Dutch population found it has an annual incidence of almost 1 percent of the general population and affects women and middle-aged persons more often.

A 2005 survey of three U.K. cities puts the rate at 8 percent, while a 2006 one conducted in France came up with 5 percent.

Chronic pain affects more than day-to-day functioning. A study last year published in the Journal of Neuroscience found that people with chronic back pain or CRPS have smaller hippocampi than healthy people.

The hippocampus plays a crucial role in processing information, memory, and spatial navigation.

Current Treatments Hit-or-Miss

While researchers are slowly forming a better idea of what causes neuropathic pain, the research has been hard to translate into medical practice, leaving many patients feeling hopeless. Part of the reason is that there are likely a variety of causes that depend on the patient’s history of injury, lifestyle, and drug history.

Tricyclic antidepressants and anticonvulsants are the common, first-line drugs used to treat neuropathic pain.

According to a 2005 study, tricyclic antidepressants will give relief to one in every two to three patients with peripheral neuropathic pain, which is superior to serotonin noradrenaline reuptake inhibitors (SNRIs), which are successful in one in every four to five, and selective serotonin reuptake inhibitors (SSRIs), good for one in every seven patients.

Anticonvulsants have not been found to be more effective than tricyclic antidepressants with an efficacy rate about the same as that of SNRIs.

Emerging Treatment

Patients who fail to find relief may have a new treatment option to turn to.

A 2006 study in the American Journal of Therapeutics found that 85 percent of neuropathic pain patients who underwent outpatient ketamine infusion saw improvements in their conditions. Just over half of the study participants reported continued relief one month after discontinuing treatment.

Known more popularly for its abuse as a club drug, ketamine has been recognized and used for several decades as an anesthetic. It works to stop the transmission of pain by blocking N-methyl-D-aspartate (NMDA) receptors. Recent research has identified hyperactivity of these receptors as a possible factor in generating neuropathic pain.

Few medical establishments in the United States administer ketamine infusions. While it does not cure neuropathic pain conditions, treatment can put the patient into remission long enough to give the nervous system a chance to repair itself.

Despite the drug itself being inexpensive, the cost of ketamine infusion runs the gamut, from $200 to $2,000 per session in outpatient clinics.

Very rarely, hospitals offer it as an in-patient option, which, factoring in all overhead, runs an average of $25,000 for a five-day course of treatment, according to American RSD Hope, an association of neuropathic pain sufferers. However, a Web search revealed that none of the country’s largest medical institutions currently offers the therapy as more than part of clinical research.

Outpatient options are more cost-effective but take several hours a day, for a week or so.

Dr. Glen Z. Brooks, who runs a ketamine infusion clinic in New York, first offers an initial session to see if the patient responds. If it’s positive, Brooks recommends a series of six more treatments over the next eight days, either consecutively or every other day. Following that, the patient may return for single treatments for maintenance as needed. Typically, doctors charge $200 to $1,000 for each session.

Brooks, trained as an anesthesiologist, treats patients by referral only.

From March 2012, his practice was offering anesthesia-assisted opiate detox. It was during this time he discovered ketamine’s benefits on pain.

“Some of my patients were addicted to pain medications because they were having problems with chronic pain,” he said. “I noticed that if during their eight-hour detox procedure I added ketamine into the infusion, there were often dramatic improvements on their chronic pain following detox.”

In September 2012, he changed his practice over to ketamine therapy entirely, and sees patients with treatment-resistant depression and neuropathic pain.

“It stops the transmission of pain from the body to the spine and to the brain, and gives the system the chance to reboot,” said Brooks.

Of CRPS patients, he said, 80 percent see dramatic reduction in their pain with lasting improvement, and 20 percent do not.

Ketamine: Reinventing Chronic Pain Management

Ketamine: Reinventing Chronic Pain Management

Ketamine: Reinventing Chronic Pain Management



Author: Jeannette Y. Wick, RPh, MBA, FASCP

For patients who respond poorly or incompletely to opioids, ketamine may be the answer. In the middle of the past century, phencyclidine hydrochloride—called PCP or angel dust on the street—was developed to be a safe, effective anesthetic that did not cause cardiovascular and respiratory depression. However, its propensity to cause convulsions at high doses and long-lasting psychoactive side effects during emergence from anesthesia destroyed its potential.

Ketamine—a PCP derivative—was synthesized in 1963 and was tested on 20 prison volunteers in 1965. One-tenth as potent as PCP, ketamine was intended to induce anesthesia like PCP, but with greater specificity and fewer side effects.

.1 The FDA approved it in 1970, and its widespread use in the Vietnam conflict theater catapulted its popularity

.2 Today, ketamine is used less and less in the operating suite

.3 Although ketamine’s psychomimetic side effects are milder than those of PCP, they can be problematic (Table 12-10).

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Recreational abuse has dogged ketamine since its approval. Abusers have injected, inhaled, and smoked ketamine, revealing characteristics of the drug that would otherwise remain unknown. Researchers hypothesize that abusers may develop tolerance because ketamine induces liver enzymes.11 Abusers rarely experience withdrawal, instead reporting a sensation called the K-hole—a constellation of visual hallucinations, dissociation, and out-of-body, and sometimes, near-death experiences. Heavy, prolonged ketamine use can cause cognitive and psychological impairment.4,12-15

Up to one-third of chronic ketamine abusers develop dose-dependent urinary tract symptoms within weeks to years: lower urinary tract irritation (vesicopathy), hydroureter, and hemorrhagic or ulcerative cystitis.13,16,17

The symptom etiology remains unclear, but may be direct toxic damage, immune system activation, or the effect of unknown bacteria.16,18

Long-term complications include hepatotoxicity (jaundice, itching, or elevated liver enzyme levels, especially in alcoholic patients) and/or cholangiopathy.19,20

Some long-term abusers develop corneal edema.21

These complications reverse after cessation of ketamine use.17,20,21

Clinically, the most common side effects of ketamine are inebriation, mental alteration, headache, hypertension, and altered liver enzymes.22

Newer, cleaner drugs or biologics are replacing ketamine in the operative suite. Yet ketamine is finding a new place in clinical therapy. Ketamine, an N-methyl-D-aspartate (NMDA)–receptor antagonist, is becoming an option for perioperative pain management among patients with opioid tolerance, acute hyperalgesia, and chronic neuropathic pain.1

NMDA Receptors

NMDA receptors are 1 of 3 glutamategated ion receptors. Gated by a magnesium ion, they normally open only briefly to allow calcium ions and other cations to enter the cell. Calcium activates second- messenger systems, causing neuronal hyperactivity.1,22-24 NMDA receptors may be involved in neuronal survival and maturation, synaptic plasticity, and memory. Abnormal NMDA function may cause neurologic disorders including Alzheimer’s disease, amyotrophic lateral sclerosis, depression, epilepsy, multiple sclerosis, Parkinson’s disease, and schizophrenia.25 Unrelenting NMDA receptor excitation allows continuous calcium influx into the cell and creates hyperexcitability. This presents clinically as opioid tolerance, hyperalgesia, and allodynia.22,26,27

Ketamine is the most potent clinically available, uncompetitive, open-channel NMDA-receptor blocker (it only works if the receptor is activated and the channel is open). Ketamine depresses the thalamus and limbic systems, preventing central nervous system centers from receiving or processing sensory input. This creates anesthesia, analgesia, and amnesia, and sometimes unpleasant psychomimetic effects or emergence phenomena.23,28,29

Sympathetic cardiovascular stimulation caused by ketamine is unique among intravenous anesthetics: it inhibits neuronal catecholamine reuptake, thereby increasing heart rate, cardiac output, and systemic and pulmonary blood pressure.30,31 Theoretically, ketamine use should be avoided in patients with prolonged QT syndrome.32 Ketamine inhibits neuronal serotonin reuptake, causing an emesis that is reversed by 5-HT–receptor blockers.33,34

What Route?

To minimize adverse events associated with ketamine use, researchers are examining the use of administration routes other than intravenous. Oral ketamine, as an injectable liquid or a compounded product, is subject to hepatic first-pass metabolism and is less effective than parenteral doses. It also lacks a clear dose-response relationship.22,35 Some study results suggest that the oral route leads to few side effects.36 Topical formulations of ketamine or ketamine with other potential analgesics has been used for managing several painful conditions (eg, pelvic pain, pruritus) with mixed results.22,37-39

Managing Pain

Ketamine use in pain management evolved from its perioperative use. Perioperative pain is expected, but may have physical or psychological consequences that delay rehabilitation and prolong hospitalization.1 Most surgeons use opioids to treat postoperative pain and supplement with regional anesthesia, other analgesics, and adjuvant agents as needed.1,23,40 Some patients respond poorly or incompletely to opioids; ketamine may help these patients.26,27,41

In low doses, NMDA-receptor antagonists can provide analgesia and circumvent opioid-related tolerance, hyperalgesia, and allodynia.10,23,40 Randomized, placebo-controlled, double-blind clinical trials (RCTs) have found that perioperative subanesthetic doses of ketamine added to opioid analgesia improved pain scores and reduced opioid consumption by approximately 30% to 50%. Ketamine was given as an intermittent low-dose intravenous bolus or a continuous infusion. It reduced opioid-related nausea and vomiting and added no additional significant adverse effects.42,43

Ketamine can also be given with morphine patient-controlled analgesia, contributing a morphine-sparing effect. Patients with chronic neuropathic pain, opioid dependence or tolerance, and acute hyperalgesia seem to benefit more.42,43 Low-dose ketamine administered before the surgical incision can lead to better analgesia for 24 hours after surgery.1 Most studies report no significant increase in psychomimetic adverse effects when ketamine is added to morphine.42,43

Sickle Cell Crisis and Chronic Noncancer Pain

Acute sickle cell disease creates severe pain with a neuropathic element. Several published guidelines recommend using opioids as first-line treatment, but some patients are unresponsive to even high opioid doses. Rapidly escalating opioid doses may induce acute tolerance and opioid-induced hyperalgesia.29,44 Case studies (but no RCTs) indicate that adding a low-dose ketamine infusion to opioids can improve pain in sickle cell disease.44 Usually, NMDA receptors activate continually only after a severe, sustained painful stimulus allows sufficient glutamate release. This is why ketamine may be useful as an adjuvant in several types of chronic central and peripheral neuropathic pain (Table 223,45,46).

Several of ketamine’s properties may prevent chronic pain from developing:

Dampening of nociception
Prevention or attenuation of hyperalgesia, allodynia, and tolerance
Attenuating central sensitization and windup phenomenon from repeated noxious stimuli when previously nonpainful stimuli become exaggerated and painful23,40

Clinicians have used short-term subanesthetic doses of ketamine to treat neuropathic pain.45 Scheduled infusions over several days can improve pain scores in patients with chronic pain; a few studies report pain relief persisting for weeks following treatment, indicating that ketamine may be disease modifying.46

Cancer Pain

Limited but increasing data support ketamine use in refractory cancer pain. Adding a small dose of ketamine to opioid therapy in a patient with opioid tolerance, called burst therapy, can improve pain management.12,47 Patients on highdose opioids whose cancer pain has a neuropathic component may respond to oral ketamine.48 Adding a small dose of ketamine to patient-controlled morphine seems to improve pain management, and some researchers are testing a ketamine mouthwash for mucositis.49,50


Large, well-designed RCTs are needed to confirm the analgesic role of ketamine. Most studies suggest, and experts believe, that ketamine use should be reserved for patients in whom opioids, anticonvulsants, or antidepressants have failed.3,36 Because pain management is an off-label use for ketamine, clinicians should consult with field experts for dosing recommendations.

Ms. Wick is a visiting professor at the University of Connecticut.
1. Corssen G, Domino EF. Dissociative anesthesia: further pharmacologic studies and first clinical experience with the phencyclidine derivative CI-581. Anesth Analg. 1966;45:29-40.
2. Mathew SJ, Shah A, Lapidus K, et al. Ketamine for treatment resistant unipolar depression: current evidence. CNS Drugs. 2012;26:189-204.
3. Hardy JR, Spruyt O, Quinn SJ, Devilee LR, Currow DC. Implementing practice change in chronic cancer pain management: clinician response to a phase III study of ketamine. Intern Med J. 2014;44(6):586-591.
4. Aroni F, Iacovidou N, Dontas I, et al. Pharmacological aspects and potential new clinical applications of ketamine: reevaluation of an old drug. J Clin Pharmacol. 2009;49:957-964.
5. Morgan CJ, Curran HV; Independent Scientific Committee on Drugs. Ketamine use: a review. Addiction. 2012;107:27-38.
6. Benitez-Rosario MA, Feria M, Salinas-Martin A, et al. A retrospective comparison of the dose ratio between subcutaneous and oral ketamine. J Pain Symptom Manage. 2003;25:400-402.
7. Ryu HG, Lee CJ, Kim YT, et al. Preemptive low-dose epidural ketamine for preventing chronic postthoracotomy pain: a prospective, double-blinded, randomized, clinical trial. Clin J Pain. 2011;27:304-308.
8. Barros GA, Miot HA, Braz AM, et al. Topical (S)-ketamine for pain management of postherpetic neuralgia. An Bras Dermatol. 2012;87:504-505.
9. Chong C, Schug SA, Page-Sharp M, et al. Development of a sublingual/oral formulation of ketamine for use in neuropathic pain: preliminary findings from a three-way randomized, crossover study. Clin Drug Investig. 2009;29:317-324.
10. Weber F, Wulf H, Gruber M, et al. S-ketamine and S-norke-tamine plasma concentrations after nasal and i.v. administration in anesthetized children. Paediatr Anaesth. 2004;14:983-988.
11. Reich DL, Silvay G. Ketamine: an update on the first twenty-five years of clinical experience. Can J Anaesth. 1989;36:186-197.
12. Loftus RW, Yeager MP, Clark JA, et al. Intraoperative ketamine reduces perioperative opiate consumption in opiate-dependent patients with chronic back pain undergoing back surgery. Anesthesiology. 2010;113:639-646.
13. Chen CH, Lee MH, Chen YC, et al. Ketamine-snorting associated cystitis. J Formos Med Assoc. 2011;110:787-791.
14. Schönenberg M, Reichwald U, Domes G, et al. Effects of peritraumatic ketamine medication on early and sustained posttraumatic stress symptoms in moderately injured accident victims. Psychopharmacology. 2005;182:420-425.
15. Morgan CJ, Muetzelfeldt L, Curran HV. Consequences of chronic ketamine self-administration upon neurocognitive function and psychological wellbeing: a 1-year longitudinal study. Addiction. 2010;105:121-133.
16. Wood D, Cottrell A, Baker SC, et al. Recreational ketamine: from pleasure to pain. BJU Int. 2011;107:1881-1884.
17. Middela S, Pearce I. Ketamine-induced vesicopathy: a literature review. Int J Clin Pract. 2011;65:27-30.
18. Chu PS, Ma WK, Wong SC, et al. The destruction of the lower urinary tract by ketamine abuse: a new syndrome? BJU Int. 2008;102:1616-1622.
19. Bell RF. Ketamine for chronic noncancer pain: concerns regarding toxicity. Curr Opin Support Palliat Care. 2012;6:183-187.
20. Seto WK, Ng M, Chan P, et al. Ketamine-induced cholangiopathy: a case report. Am J Gastroenterol. 2011;106:1004-1005.
21. Wai M, Chan W, Zhang A, et al. Long-term ketamine and ketamine plus alcohol treatments produced damages in liver and kidney. Hum Exp Toxicol. 2012;31:877-886.
22. Azari P, Lindsay DR, Briones D, Clarke C, Buchheit T, Pyati S. Efficacy and safety of ketamine in patients with complex regional pain syndrome: a systematic review. CNS Drugs. 2012;26:215-228.
23. Visser E, Schug SA. The role of ketamine in pain management. Biomed Pharmacother. 2006;60:341-348.
24. Wollmuth LP, Sobolevsky AI. Structure and gating of the glutamate receptor ion channel. Trends Neurosci. 2004;27:321-328.
25. Lipton SA. Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond. Nat Rev Drug Discov. 2006;5:160-170.
26. Rodríguez-Muñoz M, Sánchez-Blázquez P, Vicente-Sánchez A, et al. The mu-opioid receptor and the NMDA receptor associate in PAG neurons: Implications in pain control. Neuro-psychopharmacology. 2012;37:338-349.
27. Orser BA, Pennefather PS, MacDonald JF. Multiple mechanisms of ketamine blockade of N-methyl-D-aspartate receptors. Anesthesiology. 1997;86:903-917.
28. Bhutta AT. Ketamine: a controversial drug for neonates. Semin Perinatol. 2007;31:303-308.
29. Zempsky WT, Loiselle KA, Corsi JM, et al. Use of low-dose ketamine infusion for pediatric patients with sickle cell disease-related pain: a case series. Clin J Pain. 2010; 26:163-167.
30. Craven R. Ketamine. Anaesthesia. 2007;62:48-53.
31. Waxman K, Shoemaker WC, Lippmann M. Cardiovascular effects of anesthetic induction with ketamine. Anesth Analg. 1980;59:355-358.
32. Mikesell CE, Atkinson DE, Rachman BR. Prolonged QT syndrome and sedation: a case report and a review of the literature. Pediatr Emerg Care. 2011;27:129-131.
33. McNulty JP, Hahn K. Compounded oral ketamine. Int J Pharm Compd. 2012;16:364-368.
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36. Hocking G, Cousins MJ. Ketamine in chronic pain management: an evidence based review. Anesth Analg. 2003;97:1730-1739.
37. Kopsky DJ, Keppel Hesselink JM, Bhaskar A, Hariton G, Romanenko V, Casale R. Analgesic effects of topical ketamine [published online May 22, 2014]. Minerva Anestesiol.
38. Poterucha TJ, Murphy SL, Rho RH, et al. Topical amitriptyline-ketamine for treatment of rectal, genital, and perineal pain and discomfort. Pain Physician. 2012;15:485-488.
39. Poterucha TJ, Murphy SL, Sandroni P, et al. Topical amitriptyline combined with topical ketamine for the management of recalcitrant localized pruritus: a retrospective pilot study. J Am Acad Dermatol. 2013;69:320-321.
40. De Kock MF, Lavand’homme PM. The clinical role of NMDA receptor antagonists for the treatment of postoperative pain. Best Pract Res Clin Anaesthesiol. 2007;21:85-98.
41. Kaneria A. Opioid-induced hyperalgesia: when pain killers make pain worse [published online June 4, 2014]. BMJ Case Rep.
42. Bell RF, Dahl JB, Moore RA, et al. Perioperative ketamine for acute postoperative pain. Cochrane Database Syst Rev. 2010:CD004603.
43. Laskowski K, Stirling A, McKay WP, et al. A systematic review of intravenous ketamine for postoperative analgesia. Can J Anaesth. 2011;58:911-923.
44. Neri CM, Pestieau SR, Darbari DS: Low-dose ketamine as a potential adjuvant therapy for painful vaso-occlusive crises in sickle cell disease. Paediatr Anaesth. 2013;23:684-689.
45. Bell RF. Ketamine for chronic non-cancer pain. Pain. 2009;141:210-214.
46. Noppers I, Niesters M, Aarts L, et al. Ketamine for the treatment of chronic non-cancer pain. Expert Opin Pharmacother. 2010;11:2417-2429.
47. Ben-Ari A, Lewis MC, Davidson E. Chronic administration of ketamine for analgesia. J Pain Palliat Care Pharmacother. 2007;21:7-14.
48. Sear JW. Ketamine hepato-toxicity in chronic pain management: another example of unexpected toxicity or a predicted result from previous clinical and pre-clinical data? Pain. 2011;152:1946-1947.
49. White MC, Hommers C, Parry S, Stoddart PA. Pain management in 100 episodes of severe mucositis in children. Paediatr Anaesth. 2011;21:411-416.
50. Ryan AJ, Lin F, Atayee RS. Ketamine mouthwash for mucositis pain. J Palliat Med. 2009;12:989-991.

Weekly Breaking Research Updates

Weekly Breaking Research Updates

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.


[PDF] Transscalene Brachial Plexu Approach for Brachial Plexus

SR Totawar – Age, 2015

tchy action of the block, the block was converted to general anesthesia. If in case surg e effect

of the block wore off, rescue analgesia with intravenous ketamine given. In the circumstance

of nesthesia. If in case surgery was unduly us ketamine given.


Giuseppe D’Agostino1, 2*, Claudia Cristiano1, 2, 3, David J. Lyons2, Rita Citraro4, Emilio Russo4

C Avagliano, R Russo, GM Raso, R Meli, G De Sarro… – 2015

pharmacological PPAR-α agonist treatment in mice improves behavior in a pharmacological

model of ketamine-induced behavioral dysinhibition and repetitive behavior in BTBR T+ tf/J mice.

Keywords: lipids; nuclear receptor; ketamine; memory; neurodevelopmental disorders;


[PDF] Efficacy conventional intersc approach Vs novel transscal of brachial plexus block

SR Totawar – 2015

In the circumstance of inad anaesthesia. If in case surgery was undu intravenous

ketamine given. If in case surgery was unduly prolonged and the effect of the block

wore off, rescue analgesia with intravenous ketamine given.


Radiofrequency Ablation of the Pancreas: Protective Effect of Local Cooling Techniques

A Geranios, E Pikoulis, A Papalois, M Kontos… – The American Surgeon, 2015

1). Surgical Procedure The animals were anesthetized with ketamine (15–20 mg/kg) and

midazolam (0.5 mg/kg) in- tramuscularly and then intubated. The maintenance of anesthesia

was achieved by thiopental (3.5 mg/kg/hr) and fentanyl (15 mg/kg/hr).


[HTML] Original Study Enhancement of Acute Tendon Repair Using Chitosan Matrix

E Melamed, BG Beutel, D Robinson – Am J Orthop, 2015

Tikva, Israel. The rats were anesthetized with ketamine 90 mg/kg and xylazine 10

mg/kg, both administered intramuscularly, and anesthesia was prolonged as needed

with 2% isoflurane, administered by nose cone. The skin


[PDF] Cyclosporine A Reduces Glial Scarring and Facilitates Functional Recovery Following Transient Focal Ischemia

HCS Abeysinghe, L Bokhari, GJ Dusting, C Roulston – J Neurol Neurophysiol, 2015

food and water. Rats were anaesthetized using a mixture of Ketamine/Xylazine

(75 mg/kg: 10 mg/kg respectively ip) and maintained throughout surgery by inhalation

of isoflurane (95% oxygen and 5% isoflurane). A 23-gauge


Antiseizure medications

S Sanders – Seizures in Dogs and Cats

felbamate (FBM); ketamine (KET); lacosamide (LCM). Summary. The uncommon drugs include

felbamate (FBM), ketamine (KET), lacosamide (LCM), and propofol (PRO). Some of the rarely

used drugs are carbamazepine, ethosuximide, and valproic acid. Get PDF (344K).


Chronic neurokinin-1 receptor antagonism fails to ameliorate clinical signs, airway hyper-responsiveness or airway eosinophilia in an experimental model of feline …

M Grobman, A Graham, H Outi, JR Dodam, CR Reinero – Journal of Feline Medicine …, 2015

23 Briefly, ketamine (30 mg IV) was used as a premedicant, propofol was used for induction

(6 mg/kg) and maintenance (0.3 mg/kg/min), and cisatracurium (0.1 mg/kg IV of with additional

doses of 0.01–0.02mg/kg titrated to effect) was administered for neuromuscular blockade.


[PDF] Evaluation of Anti-inflammatory and Analgesic Activities of Cymbopogon citratus in vivo-Polyphenols Contribution

R Garcia, JP Ferreira, G Costa, T Santos, F Branco… – Research Journal of …, 2015

Ketamine (Ketalar, 7.7 mg kgG )1 was purchased from Parke-Davis, Pfizer (Seixal,

Portugal) Chlorpromazine (Largatil, 2.3 mg kgG )1 was purchased from

Rhône-Poulenc Rores, Laboratório Vitória SA (Amadora, Portugal).


Acute neurokinin-1 receptor antagonism fails to dampen airflow limitation or airway eosinophilia in an experimental model of feline asthma

M Grobman, S Krumme, H Outi, JR Dodam… – Journal of Feline Medicine …, 2015

19 Briefly, ketamine (30 mg IV) was used as a premedicant, propofol was used for induction

(6 mg/kg) and maintenance (0.3 mg/kg/min), and cisatracurium (0.1mg/kg IV, with additional doses

of 0.01–0.02 mg/kg titrated to effect) was administered for neuromuscular blockade.


Radiofrequency Ablation (RFA)


Radiofrequency Ablation of the Pancreas: Protective Effect of Local Cooling Techniques

A Geranios, E Pikoulis, A Papalois, M Kontos… – The American Surgeon, 2015

Pancreatic carcinoma is one of the commonest malignant diseases today and the majority of

patients are suitable for palliative treatment only. Radiofrequency ablation (RFA) has been

used extensively for the treatment of solid organ tumors but little is known on the efficacy


Effects of renal denervation from the intima and the adventitia of renal arteries on renal sympathetic nerve activity in dogs: a comparative study

M Bai, C Yang, C Gao, X Wang, H Liu, Y Zhang, J Liu… – Cardiology, 2015

A cardiac radiofrequency ablation catheter was then applied to ablate the adventitia from the

outside, also of 8 W or less and lasting up to 2 min each to obtain up to six ablations separated

both longitudinally and rotationally, which was the same as the ablation of renal


[PDF] Laryngopharyngeal Reflux: a Syndrome that Mimics Asthma

M Merchant – Proceedings of UCLA Healthcare, 2015

Surgical options include minimally invasive procedures such as radiofrequency ablation of the

lower esophageal sphincter as well as endoscopic Nissen Fundoplication, a procedure where

the surgeon wraps the stomach around the distal esophagus to create a tight valve.


Helical DeNervation Ablation Catheter Apparatus

J Mogul – US Patent 20,150,126,992, 2015

sympathetic nerves which run through the adventitia of the renal arteries using radiofrequency

(RF) energy The catheter’s RF-ablation electrode(s) will then be deployed by movement of the

slider the endoluminal, or inner arterial, surface of the artery in order to ablate the renal


Method and Apparatus for Tissue Ablation

VK Sharma, H Jabs – US Patent 20,150,126,990, 2015

can use one or more sources of infrared, electromagnetic, acoustic or radiofrequency energy

to anal canal; engaging the targeted hemorrhoid by suctioning the hemorrhoid into the ablation

device; and, delivering the ablative agent to the hemorrhoid to ablate the hemorrhoid


[PDF] N. Ayez1, EP van der Stok1, DJ Grünhagen1, J. Rothbarth1, E. van Meerten2, AM Eggermont3, C. 5 Verhoef1 6 7

DJ Grünhagen – 2015

Local treatment was performed in 122 170 patients (47%) (surgery, radiofrequency ablation,

stereotactic radiotherapy), 112 patients (43%) had 171 palliative chemotherapy and 29 patients

(11%) received neither chemotherapy nor local treatment. 172



M Jurna, JA Palero, MR Horton – US Patent 20,150,126,913, 2015

The modifier is configured to decrease the electrical impedance for the radiofrequency energy,

in particular exploited concurrent with and/or directly subsequent to the burning and/or ablation

step and as the aforementioned 70° C., and/or the laser is used to ablate skin portions


Operative Techniques in Thoracic and Esophageal Surgery

M Hawn – 2015


Apparatus and Methods Related to Constrained Deployment of Cryogenic Balloons for Limited Cryogenic Abiation of Vessel Walls

B Kelly, J Kelly, G Kelly, B Mullins – US Patent 20,150,126,986, 2015

As compared to ablation lesions formed via radiofrequency energy, cryotherapy typically utilizes

much less power vessel wall and thus results in a smaller nominal treatment area/ablation pattern

than In another embodiment (not shown), if it is desired to ablate more than half of


[PDF] Long-term efficacy of radiofrequency ablation compared to surgical resection for the treatment of small hepatocellular carcinoma

X Bu, Z Ge, J Ma, S Guo, Y Wang, J Liu

Xiangyang Bu1,2*, Zhong Ge3*, Jian Ma4, Shanyuan Guo5, Yi Wang3, Jun Liu6 1Department

of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Jinan 250021, China; 2Department

of Hepatobiliary Surgery, Qingdao Municipal Hospital, Qingdao 266011, China;


Complex Regional Pain Syndrome (CRPS/RSD)


Evolving Chinese Restaurant Processes for Modeling Evolutionary Traces in Temporal Data

P Wang, C Zhou, P Zhang, W Feng, L Guo, B Fang – Advances in Knowledge …, 2015

To model cluster branching over time, ECRP lets each cluster in current epoch form a Chinese

Restaurant Process (CRP) and uses the combination of cluster-specific CRPs as the prior for

clusters in the next epoch. where ωt−1,k and ωt,O are the weights of CRPs.


Practical Problems With Clinical Guidelines for Breast Cancer Prevention Based on Remaining Lifetime Risk

AS Quante, AS Whittemore, T Shriver, JL Hopper… – Journal of the National …, 2015

To evaluate discrimination, we computed the overall AUC and we plotted case risk

percentiles (CRPs, also called standardized placement values) (21) for the subjects who

developed breast cancer within 10 years of recruitment (case patients).



S Arimori – US Patent 20,150,126,516, 2015

A01N43/58. Related US Applications: 20040209906, Composition comprising


October, 2004, Cavazza et al. 20070249732, USE OF CERTAIN


[PDF] News from the Patient Liaison Committee: The brave new world ‘How are pain services evolving–the impact on patients?’

A Chuter – Reltebon® Oxycodone Prolonged-release Tablets, 2015

Page 16. March 2015 Vol 13 No 1 l Pain News 13 Pain News 2015, Vol 13 (1)

13–14 © The British Pain Society 2015 News After months of planning by Geraldine

Granath, Colin Preece, Liz Killick, Austin Leach and Antony Chuter



KD Benson, VR Lucente, JR Miklos – US Patent 20,150,126,894, 2015

Neuromodulation has also been used safely and effectively to help relieve chronic back pain,

pain from cancer and other nerve injuries, and pain from Complex Regional Pain Syndrome

(CRPS) and Reflex Sympathetic Dystrophy (RSD), greatly improving the quality of life for



EV Smith-Forbes – 2015

Multi-joint Fracture Multiple 0.0% 0.0% 0.0% 2.0% CRPS 0.0% 0.0% 0.0% 1.6% Nerve Injury

0.0% 0.0% 0.0% 1.2% MCID= minimal clinical important difference, DRUJ= distal radio-ulnar

joint, CRPS = complex regional pain syndrome, ROC = receiver operator characteristics


[PDF] Temperature Dependent Dielectric Model at 1.4 GHz for an Agricultural Soil Thawed and Frozen

VL Mironov, AY Karavaysky

0.513 The results of validation measurements for the soil CRPs are displayed in

Fig. range. To obtain the error of the developed model, we correlated the predicted

CRPs with the ones especially measured for validation. In Fig.


[PDF] A Bayesian A Bayesian Beta Markov Random Beta Markov Random Field Calibration of the Term structure of implied risk neutral densities densities

R Casarin, FR Casarin, F Leisen, GMGMG Molina…

Page 1. A Bayesian A Bayesian Beta Markov Random Beta Markov Random Field Calibration

of the Term structure of implied risk neutral densities densities Roberto Casarin, Fabrizio Roberto

Casarin, Fabrizio Leisen, German Molina German Molina German Molina,





[PDF] Heart rate turbulence analysis in female patients with fibromyalgia

O Solak, H ToktasIV – 2015

OBJECTIVE: Fibromyalgia is characterized by diffuse musculoskeletal pain and discomfort.

There are several reports regarding autonomic nervous system dysfunction in patients with

fibromyalgia. Heart rate turbulence is expressed as ventriculophasic sinus arrhythmia and



ME Platt – Alternative Medicine, 2015

Abstract From a survival standpoint, the body always wants to make sure the brain has

enough fuel.[…] any time the body detects a low amount of fuel in the brain, it releases

adrenaline to raise sugar levels.[…] use of these methods often leads to a cure for


[PDF] Association of Impaired Sleep Quality in Patients With Burning Mouth Syndrome: A Case-Control Study

F Arbabi-Kalati, NM Bakhshani, B Tahmtan… – 2015

deprivation. Sleep deprivation can also lead to mood changes, insomnia and fatigue,

affecting pain sensation (2). Patients with known fibromyalgia have a lower noc- turnal

sleep quality compared to controls and have more insomnia


Dizziness, Lightheadedness, and Syncope in a Patient with Type 2 Diabetes

S Paturi, JL Gilden, F FCP – Diabetes Case Studies: Real Problems, Practical …, 2015


Vagally mediated heart rate variability in headache patients—a systematic review and meta-analysis

J Koenig, DWP Williams, AH Kemp, JF Thayer – Cephalalgia, 2015

capabilities (21). Lower vmHRV is reported in a variety of chronic painful conditions,

such as chronic neck pain (22), chronic pelvic pain (23), complex regional pain (24),

fibromyalgia (25,26) and irritable bowel syndrome (27). In


Novel Therapeutic Uses of Mu-Opiate Receptor Peptides

TE Maione – US Patent 20,150,126,455, 2015

pain. 16. The method, according to claim 1, used to reduce chronic noncancer pain

selected from pain associated with arthritis, neuropathy, low back pain, osteoarthritis,

fibromyalgia, headache, and diabetic neuropathy. 17.


Brain-gut axis: gastroenterology-IBS

J Wright – The Specialist Forum, 2015

to controls. Interestingly, this hypoalgesia was even greater in patients with concomitant

fibromyalgia, suggesting a commonality between these two symptom-driven diagnoses.

Anticipatory factors may also play a part. In experiments


[PDF] A Pilot Study Measuring Outcomes of Managing Fascial Health for Individuals With Fibromyalgia

KB Segarra

Abstract This article examines the outcomes of managing fascial health for persons

diagnosed with fibromyalgia based on the protocol developed by the author, Dr. Kirstie

Bender Segarra, and implemented in a pilot study of five clients. The protocol was


[PDF] The Somatosensory Amplification in Vitiligo and Chronic Urticaria Patients: A Controlled Study

M Sukan, F Maner – J Neurol Disord, 2015

Amplification may be a pathogenic mechanism in certain specific amplification

disorders such as fibromyalgia and irritable bowel syndrome [9]. Some individuals

are generally more sensitive to bodily sensation than others.


Psychotherapy and mental health as a psychological science discipline

HU Wittchen, S Härtling, J Hoyer – Verhaltenstherapie, 2015

which behavioural factors play a significant role in the initiation, maintenance and rehabilitation,

such as cancer (eg [Fors et al., 2011]), cardiovascular disease (eg [Gulliksson et al., 2011]),

metabolic disease and obesity (eg [Grilo et al., 2012]), and fibromyalgia [Kashikar-Zuck et

Cannabinoids for neuropathic pain conditions

Cannabinoids for neuropathic pain conditions

Neuropathic pain is often very difficult to treat with current Food and Drug Administration (FDA)-approved analgesics.  The most commonly prescribed medication to treat these chronic pain conditions is opioids.  Opioids have very limited efficacy in patients with chronic neuropathic pain conditions.  This has sparked research into new targets for the treatment of these patients.  Promising research by investigators at the Cleveland Clinic demonstrated that microglial inflammation is a common pathway for neuropathic pain and other treatment-resistant neuroinflammatory conditions, such as Alzheimer’s disease (AD).

“Microglial inflammation is a mechanism of many CNS disorder – neuropathic pain, Alzheimer’s disease, multiple sclerosis, parkinsonism, you name it,” said lead researcher Mohamad Naguid, MD, of Cleveland Clinic’s Anesthesiology Institute, Department of Pain Management.

Subsequently, this team of researchers has synthesized a molecule called MDA7, which is a cannabinoid type 2 (CB2) receptor-selective agonist.  Preliminary studies with this new drug candidate have shown that it can inhibit microglial activation and recruitment, which is fundamental to microglial inflammation and neuropathic pain.

Thus far, their research is in the preclinical phase.  They have shown efficacy in a rodent model of Chemotherapy-induced neuropathic pain1, CRPS (not yet published), and some promising results in an animal model of Alzheimer’s disease2.  They hope to test MDA7 in humans as a next step.  The team is very hopeful that their preclinical results translate well to the clinic.  Only time will tell.


1. Naguib, M., Xu, J.J., Diaz, P., Brown, D.L., Cogdell, D., Bie, B., Hu, J., Craig, S., Hittelman, W.N., 2012. Prevention of paclitaxel-induced neuropathy through activation of the central cannabinoid type 2 receptor system. Anesthesia and analgesia 114, 1104-1120.

2. Bie, B., Wu, J., Yang, H., Xu, J.J., Brown, D.L., Naguib, M., 2014. Epigenetic suppression of neuroligin 1 underlies amyloid-induced memory deficiency. Nature neuroscience 17, 223-231.