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Fall 2014

Fall 2014

Chronic Abdominal Pain: Reduce Opioid Use, Increase Multidisciplinary Care
Sticking with Proven Practices for Low Back Pain
Microglial Inflammation: A Promising Target in Neuropathic Pain Figures in Memory Deficiency Too

Microglial Inflammation: A Promising Target in Neuropathic Pain Figures in Memory Deficiency Too

Cleveland Clinic researchers pursue a potentially treatable common pathway.

Promising research by Cleveland Clinic investigators demonstrates that microglial inflammation is a common pathway — and a potentially treatable one — for neuropathic pain and other treatment resistant neuroinflammatory conditions, including Alzheimer disease (AD).

“Microglial inflammation is a mechanism of many CNS disorders — neuropathic pain, AD, multiple sclerosis, parkinsonism, you name it,” says lead researcher Mohamed Naguib, MD, of Cleveland Clinic’s Anesthesiology Institute, which includes the Department of Pain Management. His team has synthesized a molecule called MDA7, a cannabinoid type 2 (CB2) receptor-selective agonist, to inhibit microglial inflammation in hopes of effectively treating neuropathic pain and other conditions. “MDA7 prevents microglial activation and recruitment, which represent the elemental pathway of microglial inflammation,” explains Dr. Naguib.


The researchers demonstrated as much in a 2012 paper in Anesthesia and Analgesia (2012;114[5]:1104-1120)reporting findings from a rodent model of paclitaxel-induced neuropathy, which is associated with activation of microglia followed by the activation and proliferation of astrocytes and the expression and release of pro-inflammatory cytokines. They found that MDA7 prevented paclitaxel-induced allodynia in rats and mice in a dose- and time-sensitive fashion without compromising paclitaxel’s anticancer effects. MDA7’s anti-allodynia effect was absent in CB2–/– mice and was countered by CB2 antagonists, which suggests it directly involves CB2 receptor activation.

Because all neuropathic pain shares the mechanism of microglial inflammation, Dr. Naguib expects the same effect in neuropathic pain types outside the chemotherapy setting. “We started with chemotherapy- induced neuropathy because it’s an area of unmet therapeutic need,” he says.


His team recently finished a study using a vascular occlusion model in the rat to replicate another form of chronic pain with a microglial inflammation mechanism, complex regional pain syndrome (CRPS). MDA7 was again highly effective, both at the molecular level and in terms of phenotypic response. They expect to submit the CRPS study for publication this year.


The wider biomedical community learned of the team’s work via an exciting study in February’s Nature Neuroscience (2014; 17[2]:223-231) linking microglia-mediated inflammatory changes in a postsynaptic protein, neuroligin 1, to amyloid-associated memory deficiency in rodents. Current models of AD hold that amyloid plaques accumulate in the brain, overwhelming the microglia that serve as the nervous system’s main form of active immune defense. When the microglia cannot clear out amyloid rapidly enough, they become inflamed, which leads to gene modifications in the brain.

“As our research into microglial inflammation advanced, it became clear how important this inflammation is to a variety of disease processes, which led down the Alzheimer path,” says Dr. Naguib. His team’s Nature Neuroscience study showed that the microglial inflammation induced gene changes in the brain include suppressed expression of the neuroligin 1 protein — and that this suppression leads to hippocampal glutamatergic dysfunction and memory deficiency in rodents. The effects were ameliorated by inhibiting microglial activation. “These findings link neuroinflammation, synaptic efficacy and memory, thus providing insight into the pathogenesis of amyloid-associated diseases,” the researchers concluded.

Dr. Naguib notes that much research remains, but the findings suggest that MDA7 represents a promising new therapeutic approach to AD and other conditions involving microglia-mediated neuroinflammation, such as multiple sclerosis and Parkinson disease.


In the near term, the researchers are focused on gaining funding to move MDA7 into phase 1 human studies for chemotherapy-induced neuropathy, which they hope to begin by 2015. Studies of MDA7 in animal models of AD will take longer, due to the longitudinal nature of AD, but Dr. Naguib says the team is committed to pursuing that research as well.

Spring 2014

Case Study in Chronic Pelvic Pain: All About Collaboration

Three years ago, Mrs. A (pseudonym to protect her privacy) enjoyed taking brisk three-mile walks around her neighborhood in Pittsburgh. Then, after undergoing urogynecologic surgery in late 2011, she was lucky to be able to finish a leisurely stroll around the block. Mrs. A, 59, suffers from chronic pelvic pain (CPP) dating back to that surgery. Fortunately, she has found some relief and much-needed emotional support from a multidisciplinary team of physicians at Cleveland Clinic’s Pelvic Pain Center.

Formed in 2013, the Pelvic Pain Center fosters interdisciplinary collaboration and holistic treatment of patients with CPP. Approximately 20 physicians are part of the center. They consult closely and meet quarterly to exchange experiences, present case studies, share journal articles and discuss treatment options for patients. The group includes pain management specialists, gynecologists, urologists, urogynecologists, psychiatrists and interventional radiologists.

‘Going It Alone’ Not an Option in CPP

Creation of the Pelvic Pain Center was spearheaded by Joseph Abdelmalak, MD, a member of the Department of Pain Management whose specialties include CPP. When he joined Cleveland Clinic in 2012, he began informally collaborating with colleagues in other specialties to treat patients with CPP. The condition, marked by severe and persistent pelvic pain that can be debilitating, is hard to treat because its causes are varied. CPP can be the result of one or more reproductive, urologic, gastrointestinal, psychosexual, vascular, neurologic or spinal issues. It also may have no obvious pathology.

“As a team, physicians can work much better at treating patients with CPP than individually,” says Dr. Abdelmalak. “That’s the whole idea behind the Pelvic Pain Center.” Mrs. A is just one patient who has benefited from the center’s collaborative approach.

Postsurgical Pain — and the Pain of Dismissed Complaints

In October 2011, surgeons in Pittsburgh performed a hysterectomy and laparoscopic surgery for uterovaginal prolapse on Mrs. A. Her pelvic pain began the next day. For nearly a year, she sought answers and relief from her surgeon and from a gastroenterologist and a pain management specialist. She tried various medications and pelvic physical therapy. Nothing worked. And just as troubling as the pain was the attitude of some of her physicians in Pittsburgh, whom Mrs. A says were dismissive of her complaints.

“I felt like I was free-falling,” she says. “I was pushed from the surgeon to the gastroenterologist to the pain doctor. Nobody wanted to help me.”

Relief from Coordinated Therapies

In the summer of 2012, after researching pelvic pain on the Internet, Mrs. A found a team of physicians at Cleveland Clinic willing to listen — really listen — and get to the bottom of her CPP. They include Dr. Abdelmalak as well as Marie Fidela Paraiso, MD, Head of the Center for Urogynecology and Reconstructive Pelvic Surgery, and colorectal surgeon Tracy Hull, MD.

When Mrs. A. met Dr. Abdelmalak, she felt hopeful for the first time since her pain began. “I was in his office for three hours,” she recalls. “He let me talk, and he understood my emotion and frustration.”

The team of physicians has treated Mrs. A using medical management, physical therapy, a pessary device and pelvic floor exercise. In June 2013, she underwent a laparotomy, a sigmoid resection and an augmentation of her prolapse repair. “In preparing me for surgery, there was no stone left unturned,” says Mrs. A. “They even told us where to get discount parking passes and provided hotel information.”

Since the surgery, Mrs. A has received numerous nerve blocks. While she still lives with CPP, the treatments give her some pain relief and a little better quality of life. She says she remains hopeful the relief will increase as she continues to explore additional treatments with Dr. Abdelmalak. “The big difference is that I’m not doing this alone but have a team of doctors who care and have my best interest at heart.”

To refer a patient to the Pelvic Pain Center, call 216.444.PAIN. Look for an in-depth profile of the Pelvic Pain Center in Cleveland Clinic’s print Pain Consult newsletter this summer.

Why Pain Specialists Rarely Use Opioids for Chronic Pain

As ever more scrutiny is focused on the use of opioids in the United States, two principles about their use for chronic pain should loom largest in clinicians’ minds, advises Richard W. Rosenquist, MD, Chairman of Cleveland Clinic’s Department of Pain Management:

  • The role of opioids in treating chronic pain is very small and limited to a narrow subset of patients.
  • Any plan to start a patient on opioids must include a plan to monitor their effect using specific outcome measures and to stop their use if defined treatment goals aren’t met.

“In general, pain specialists rarely prescribe opioids anymore for chronic pain unless it’s cancer-related pain,” says Dr. Rosenquist.

Overcoming a Misjudgment from a Quarter Century Ago

But it wasn’t always that way. In the late 1980s, an effort took hold among pain specialists to improve chronic pain treatment through expanded opioid use. “Opioids were known to be effective for acute pain, so the thinking was, Why not use them for patients with chronic pain who needed greater relief?” explains Dr. Rosenquist.

Many pain specialists at the time believed that if chronic opioids were limited to legitimate indications, patients would not become addicted. “But reality caught up with us,” Dr. Rosenquist notes. “We learned that people who get started on opioids have a much higher conversion to active addiction than previously thought. Also, physical dependence on opioids develops quickly, and in some people it turns into physical addiction.”

A Steep Societal Toll

These lessons did not become clear for years, however, and prescribing of opioids surged during the 1990s and early 2000s. Opioid abuse increased in tandem, and the consequences have been filling headlines for several years now:

  • 15,000 to 18,000 U.S. deaths per year attributable to prescription opioid overdose
  • The proliferation of — and later crackdown on — “pill mills” that spurred a subindustry of individuals reselling opioids for profit
  • Burgeoning rates of addiction to heroin, a less-expensive opiate that addicts turn to for cost reasons or when they can no longer access prescription opioids because of the pill mill crackdown
Other Reasons to Nix Chronic Opioids

These huge addiction-related costs are a major reason why the pain medicine community has dramatically scaled back use of opioids for chronic pain in recent years — but they are hardly the only one, says Dr. Rosenquist.

Another reason is disappointing efficacy. “People thought opioids had no ceiling effect, but it turns out they don’t yield much pain relief in the chronic setting,” he explains. “After a while, patients are lucky to get 20 or 30 percent relief.” Improvement in functional outcomes and general well-being is often even less, he adds.

Many patients on chronic opioids feel worse overall because of these agents’ now well-established side effects, including immunosuppression, endocrine abnormalities, constipation, sedation and depression. Cruelest of all, some patients experience worsened pain after starting chronic opioids, an effect known as opioid-induced hyperalgesia.

The Rare Cases When Chronic Opioids Are Indicated

So when do Dr. Rosenquist and his colleagues consider opioids outside the acute pain setting?

“We’ll look at them for managing cancer pain when we have no other alternatives,” he says (see next story). “We also will consider them when there are medical contraindications to other choices for pain control. In those cases, we use opioids in low doses and aim to maintain the dose at a steady state. In general, high doses are rarely successful.”

He adds that continued opioid use is contingent on demonstrated improvements in functional outcomes, not just pain scores. “If you give an antibiotic for a UTI and it doesn’t treat the infection, you stop it. The same principle applies. Many patients are on opioids for a long time without ever achieving a good outcome, yet they and their providers fail to question it and try something different.”

Today’s Challenge: Caring for Displaced Patients

Many of the Department of Pain Management’s current efforts surrounding opioids aim to address the needs of those patients. That’s especially true now that many unscrupulous providers have stopped prescribing opioids in the wake of regulatory crackdowns, leaving their patients desperate for new prescribers. The Department of Pain Management is implementing a new algorithm for managing these displaced patients.

The foundation of the approach is simply getting patients to the right provider after an evaluation of their pain and current opioid use status. Patients whose condition includes an addiction component need to have that addressed first, so they are referred to Cleveland Clinic’s Alcohol and Drug Recovery Center or its distinctive interdisciplinary Chronic Pain Rehabilitation Program. The latter is a three- to four-week outpatient program designed to reduce both pain and chemical dependency and foster coping skills and improved function.

Once addiction is addressed, Dr. Rosenquist’s team restarts the patient’s pain management with a proper evaluation to uncover the underlying cause of the pain process. That typically leads to multimodality treatment that may include psychological approaches, interventional approaches, physical therapy and more. “What we often offer could be called a pain wellness program.”

Beyond these efforts, the Department of Pain Management is partnering with Cleveland Clinic’s Digestive Disease and Surgery Institute and Neurological Institute to develop a novel care path and multidisciplinary clinic specifically for chronic abdominal pain. A major impetus is the prevalence of inappropriate opioid use. “I can’t think of anything with less evidence than using opioids for abdominal pain,” says Dr. Rosenquist, “so we’re aiming to tackle that problem head-on.”

In the end, he sees opioids “not as the root of all evil but something to be used very carefully. A decision to use an opioid should be made with good understanding and clear expectations about what it should do. If it doesn’t do what’s intended, stop the drug.”

Dr. Rosenquist can be reached at 216.445.8388 or

Are We Limited to Opioids When It Comes to Cancer Pain?

When one of Dr. Harold Goforth’s cancer patients developed a severe scalp zoster neuropathy, treatment with oral pain medication over six months yielded significant symptom improvement. However, the pain was periodically disabling. So Dr. Goforth, a member of Cleveland Clinic’s Solid Tumor Oncology Department, referred the patient to a pain management specialist for an occipital nerve block and a superior cervical ganglion block, which allowed for a reduction in medication.

“Most patients with cancer pain can be managed medically,” says Dr. Goforth. “But for those with incomplete symptom relief, there’s a large role for advanced pain techniques.” That’s when he calls on colleagues like Shrif Costandi, MD, of Cleveland Clinic’s Department of Pain Management.

Opioids: A Front-line Tool but Not the Only Tool

Cleveland Clinic adheres to the World Health Organization’s three-step ladder for cancer pain management, which depends on the level of pain. As a tertiary care center, Cleveland Clinic treats many cancer patients with complex pain conditions. “Opioids are usually the initial line of therapy used and are indeed an effective modality for many patients,” says Dr. Costandi.

Dr. Goforth says the majority of cancer patients can be managed medically with a combination of opioids and nonopioids. However, opioids are notorious for side effects such as excessive drowsiness, nausea, vomiting, constipation and hormonal disturbances. “We offer other interventions that aim for pain relief with improved quality of life during the patient’s life expectancy,” explains Dr. Costandi.

Three Classes of Interventional Modalities

Because cancer is a complex, progressive disease, treating cancer pain is challenging. Interventional pain management modalities play an important role, notes Dr. Costandi. He classifies them in three main categories, all of which can be used in tandem with opioids:

1) Nerve blocks. These can be divided into three broad types according to their purpose:

  • Diagnostic blocks are intended to identify pain generators. These include the transversus abdominis plane (TAP) block, which pinpoints if the pain originates from the abdominal wall (somatic) or the internal organs (visceral).
  • Prognostic blocks predict the potential benefit of ablating the blocked nerves. One type, the sympathetic nerve block, is indicated to control visceral cancer pain. Common examples are celiac plexus blocks and superior hypogastric plexus blocks.
  • Therapeutic blocks aim to alleviate pain and improve patients’ functionality. Patients who obtain short-term but substantial relief with prognostic blocks can benefit from therapeutic blocks such as a neurolytic block. Neurolytic celiac and superior hypogastric blocks are an established treatment option for upper abdominal and pelvic malignancies, respectively.

2) Vertebral interventions. These include vertebral augmentation procedures (VAPs) and the OsteoCool® RF ablation system.

VAPs are complex procedures to treat and relieve pain from compression fractures due to spinal metastasis, which is common in multiple myeloma and other cancers. There are two kinds of VAPs performed by highly trained interventional pain specialists or neurosurgeons:

  • Vertebroplasty, which involves percutaneous injection of bone cement, under image guidance, into the collapsed vertebral body
  • Kyphoplasty, which introduces an inflatable balloon into the collapsed vertebral body to restore height and create a cavity to be filled with bone cement to stabilize the bone and relieve the disabling pain

“VAP patients show significant improvement in pain almost immediately,” says Dr. Costandi. “Multiple studies have demonstrated noticeable pain reduction as well as improvement in function.”

OsteoCool is a technique that uses bipolar water-cooled radiofrequency ablation to treat spinal pain secondary to metastatic vertebral tumors. Clinical experience at Cleveland Clinic, which was among the first centers to investigate this technique, shows local disease control, marked pain reduction and quality-of-life improvements from a single treatment.

3) Implantable therapies. These modalities include implanted neurostimulators, used for selected cancer patients presenting with intractable focal neuropathic pain, and intrathecal drug delivery devices. The latter are considered for patients who fail to respond to oral opioids and may benefit from an alternate medication or who experience pain relief from opioids but are limited by severe side effects. Intrathecal pump implants optimize pain relief for patients with a life expectancy of more than three months. For patients with shorter life expectancy, a subcutaneous port with a tunneled catheter is usually placed instead.

Why Collaboration Is Critical in Cancer Pain Management

Physicians from oncology, pain management and palliative medicine work together at Cleveland Clinic to determine the best interventions for each patient. “It’s extremely important to collaborate,” says Dr. Costandi, “because each specialist brings a unique skill set and knowledge base to the patient’s care.”

“Pain control and cancer-related symptom management by palliative medicine and pain specialists is of paramount importance in achieving clinical success,” notes Dr. Goforth. “Oncologists can actually spend more time on oncology.”

“If cancer pain is refractory to conventional pharmacotherapy or if patients cannot tolerate escalating doses, physicians should definitely consider other interventions,” adds Dr. Costandi. “The goal is to improve patients’ functionality and help them enjoy the remainder of their lives. That’s the least we can offer, and they deserve it.”

Dr. Costandi sees patients at Cleveland Clinic’s main campus and the Richard E. Jacobs Health Center in Avon. He can be reached at 216.444.8455 or

Fall 2013

Spring 2013

New mild® Procedure for Lumbar Spinal Stenosis Returns a Champion to His Game

When 67-year-old Nagy Youssef sought treatment for lumbar spinal stenosis (LSS) at Cleveland Clinic, he couldn’t stand long enough to brush his teeth and could walk no farther than 500 feet before needing to sit down to relieve agonizing back and leg pain.

“In addition to the pain, I was psychologically traumatized to be in this condition,” says Mr. Youssef, an Egyptian athlete who is also known as Nagui Assad and competed in the Olympics in the 1970s and 1980s, holding a world record in shot put. Increasing severity of the LSS, an age-related degenerative disease, forced him to significantly scale back his coaching of national track and field teams, and he could no longer participate in routine activities he had taken for granted.

But all of that changed for the better since Mr. Youssef underwent an innovative X-ray-guided outpatient treatment for moderate to severe LSS — the mild® (minimally invasive lumbar decompression) procedure — at Cleveland Clinic last year. “The back pain decreased significantly, and I can now stand for more than 30 minutes and walk four miles,” he says.

Burgeoning Demand — and Medicare Coverage

“The mild procedure reduces pain and increases mobility while maintaining the structural integrity of the spine,” says Nagy Mekhail, MD, PhD, Director of Evidence-Based Medicine in the Department of Pain Management, who performed the procedure on Mr. Youssef.

Medicare began covering mild in July 2012, and a number of private insurers cover it as well.

Like Mr. Youssef, many patients who present with moderate to severe LSS cannot stand longer than a few minutes or walk more than a few hundred feet. The average age for those seeking treatment is 73 years.

“With more than 10,000 baby boomers turning 65 every day, more and more patients are seeking innovative treatments such as mild that will allow them to stay active and maintain their quality of life,” Dr. Mekhail says.

Who’s a Candidate?

LSS may be due to a bulging disc and/or hypertrophy of the ligamentum flavum, which lines the back of the spinal canal. Narrowing of the spinal canal causes nerve compression. When someone with LSS stands or walks, the canal narrows even more, causing neurogenic claudication, or low back and leg pain that is relieved with sitting or bending forward.

Patients who don’t respond to conservative treatment and are not candidates for open spine surgery may benefit from mild if they complain of neurogenic claudication and if MRI shows that a thickened ligamentum flavum is the major cause of the spinal stenosis.

The mild procedure is performed under deep sedation through a 1-cm incision. The clinician uses a special sculpting tool that glides through a portal with a diameter of 5 mm, about the size of a pen cap, to go between the bones, scrape out the ligaments and widen the spinal canal to decrease nerve compression. Patients typically recover quickly and are able to begin walking within the first 24 hours after the procedure.

Enduring Effects to Date

Dr. Mekhail and colleagues recently published findings from a multicenter study of mild (Pain Pract. 2012;12:184-193). Highlights include:

  • No major device- or procedure-related complications
  • Significant reduction in pain at one-year follow-up
  • Improvement in physical functionality and mobility (as measured by walking distance and standing time)
  • Decreased disability secondary to neurogenic claudication

As for Mr. Youssef, he is back at work as a coach and able to be more active with his grandchildren and to grocery shop with his wife again. “I feel that my life clock has been rewound to before the year 2000, when the pain started,” he says.

To refer an LSS patient for evaluation for the mild procedure, call 216.444.9114.

The Many Options for Managing Back Pain

When oral pain medications or physical therapy fail to help patients with back pain—or when there are ongoing signs of weakness—seeking further evaluation from a pain specialist is the best course of action. There are many treatment options to consider, says Shrif Costandi, MD, of Cleveland Clinic’s Pain Management Department.

“My colleagues and I base treatments and therapy on the underlying cause of your back pain,” explains Dr. Costandi. Here is rundown of common back pain causes and the interventions that can be done to manage the pain:

  • Lower back pain is often caused by degeneration of the posterior facet joints. Usually a diagnostic nerve block is done to confirm the diagnosis. If this is the cause of your pain, pain specialists will often do a radiofrequency ablation (RFA) of the nerves for long-term relief. This is removal of the nerves causing the pain using alternating electric currents. The average duration of relief from RFA is six to nine months.
  • When the nerve roots in the spine are being compressed or irritated by herniated or bulging discs (radiculopathy), this can lead to back pain shooting down the leg, along with weakness and/or numbness. If there is no improvement with oral medications, epidural steroid injections can be considered to alleviate pain, facilitate physical therapy and early return to work.
  • Pain emanating from the sacroiliac (SI) joint – the joint between the spine and hip bones- can be managed by joint steroid injections and physical therapy to strengthen core muscles. If these injections provide relief but the effect is temporary, RFA may be used.
  • Disrupted discs – or discogenic pain -- can be managed with two newer treatments. Biacuplasty is a minimally invasive procedure that applies radiofrequency heat through probes to destroy painful nerve fibers of the disc. The second option is “fibrin sealant” injections. These treatments can improve disc stability and encourage tissue repair.
  • For persistent pain after spine surgery, called postlaminectomy syndrome, epidural steroid injections are the first line of therapy after failing to respond to oral medications. These are usually done in combination with physical therapy and medical management. If these provide temporary or insufficient relief, permanent implantation of a spinal cord stimulator may be considered.
  • For spinal stenosis, oral medications are tried first, if there is no improvement then interventions are warranted. The first option is epidural steroid injections along with physical therapy. Decompression surgery also has traditionally been considered. Today a newer outpatient procedure called mild® (minimally invasive lumbar decompression) is available (see the story on the mild procedure in this issue). Cleveland Clinic studies have shown great improvements in standing time and walking distance for patients who have had the mild procedure.
  • For intractable back pain, certain pain medications can be infused around the spinal cord through an implanted programmed pump to provide adequate relief of the pain. Typically, this is done as a last resort.

In some cases, pain can be coming from a malignancy. A pain specialist can help to rule this out or help to manage it effectively with other treatments.

A Multidisciplinary Approach

Having different options to manage pain is key to successfully helping patients, Dr. Costandi believes. And so is collaboration among providers.

“We refer patients to physical therapy to supplement most medical interventions,” says Dr. Costandi. “Our patients also are seen by a pain psychologist for behavioral modification or stress-coping techniques. A multidisciplinary approach really is the best way to deal with pain.”

Dr. Costandi sees patients at Cleveland Clinic’s main campus and the Richard E. Jacobs Health Center in Avon. To make an appointment with Dr. Costandi, call 216.444.PAIN (7246).

Expanding Options for Back Pain: Matching Treatments to Causes

Patients with back pain have no shortage of minimally invasive treatment options, many of which are offered by pain specialists in Cleveland Clinic’s Department of Pain Management. The diverse interventions are aimed at restoring function and alleviating pain, even in patients with complex causes of back pain.

When conservative measures (such as oral pain medications and physical therapy) fail to adequately relieve back pain, or if red-flag signs (e.g., weakness) are present, referral for evaluation by a pain specialist should be considered. So says Shrif J. Costandi, MD, staff physician in the Department of Pain Management.

“Back pain can have nonmalignant and malignant causes,” says Dr. Costandi, “and the specific therapy must be matched to the cause.” Below is a rundown of interventions considered by Dr. Costandi and his colleagues based on the underlying cause of back pain.

Nonmalignant Causes

Facet arthropathy is a common cause of axial back pain. If it’s suspected, temporary relief from medial branch blocks can confirm the diagnosis (medial branches are nerves that supply the facet joints and cause pain), at which point pain specialists can proceed to radiofrequency ablation (RFA) of involved nerves for long-term relief. “The average duration of relief from RFA is usually six to nine months,” notes Dr. Costandi.

When radiculopathy is the cause of back pain, epidural steroid injections — either interlaminar or transforaminal — can be effective interventions to facilitate physical therapy and early return to work.

Pain emanating from the sacroiliac (SI) joint can be managed by SI joint steroid injections and physical therapy to strengthen core muscles. If SI joint injections provide relief but the effect is temporary, RFA of the lateral sacral branches may be offered.

Discogenic pain is confirmed with provocative discography, which also identifies the disrupted discs. Two new treatments offered for discogenic pain are biacuplasty and fibrin sealant injections (via the Biostat® System). Biacuplasty with the TransDiscal™ System is a minimally invasive procedure that applies radiofrequency heat through probes to the annulus of the disc to destroy painful nerve fibers. Changes in collagen fibers induced by biacuplasty may also improve disc stability. Fibrin sealant is a biologic tissue that, when applied to a disrupted disc, seals the disruption, restores disc height and encourages tissue repair. The Department of Pain Management is participating in clinical studies of the fibrin sealant; results from data analysis are promising, Dr. Costandi says.

For postlaminectomy syndrome, or persistent pain after spinal surgery, pain relief and improved function may be provided by a multidisciplinary approach that combines injections, physical therapy, psychological support and optimal medical management. If this is insufficient or provides only temporary relief, the patient may be a candidate for a trial of spinal cord stimulation. If the trial improves function and reduces pain and medication requirements, permanent implantation of the spinal cord stimulator is considered. An emerging option under study at Cleveland Clinic and just a few other centers worldwide is dorsal root ganglion stimulation, in which only the dorsal root ganglia at the exiting nerve roots are stimulated (vs. the entire dorsal sensory column of the spinal cord), allowing for more sophisticated stimulation and coverage.

For pain from spinal stenosis, if conservative management is inadequate, the first option is epidural steroid injections plus physical therapy. Decompression surgery has traditionally been considered next-line therapy, but an outpatient procedure called mild® (minimally invasive lumbar decompression) is now available. Objective improvements in standing time and walking distance have been recorded in studies of mild at Cleveland Clinic. “Patients who could barely stand for 10 minutes were up and moving around for several hours following mild,” says Dr. Costandi. “Some patients can walk a mile or two after being able to walk only 200 or 300 feet. Many can drop their canes, too.”

For intractable back pain, delivery of opioids and local anesthetics to the cerebrospinal fluid through an intrathecal pump may be tried as a last option.

Back Pain of Malignant Origin

Vertebral compression fractures can have nonmalignant (osteoporosis) as well as malignant causes. Painful fractures can be treated with kyphoplasty, a minimally invasive procedure in which cement is injected into the vertebral body to restore vertebral height and reduce pain.

Pain from vertebral metastases may be managed by a novel technique using the OsteoCool™ System, which employs water-cooled radiofrequency probes to ablate malignant bone tissue. OsteoCool therapy is an option for patients in whom radiotherapy and opioids provide inadequate relief. “Patients’ pain levels and disability scores were improved significantly,” notes Dr. Costandi.

Choice and Collaboration Are Key

The ability to choose from many interventions is key to successful individualized back pain management, says Dr. Costandi. So is collaboration. “We refer patients to physical therapy to supplement most medical interventions. If there is any psychological component, our patients are seen by a pain psychologist for behavioral modification or stress-coping techniques. A multidisciplinary approach is the best way to deal with chronic pain.”

Dr. Costandi sees patients at Cleveland Clinic’s main campus and the Richard E. Jacobs Health Center in Avon. He can be reached at 216.444.8455.

Patient, Heal Thyself: Analgesic Cell Therapy Could Be a Game-Changer in Chronic Pain

Innovative stem cell research under way at Cleveland Clinic could someday dramatically change the way chronic pain is treated and decrease the potential for prescription drug abuse.

The research is in the early stages of testing whether mesenchymal stem cells, after being harvested from a patient’s bone marrow and reprogrammed into chromaffin-like cells, can provide relief from chronic intractable pain when they are transplanted back into the same patient.

Innovative Approach

The endogenous opioids that are generated from these differentiated chromaffin-like cells have powerful analgesic effects. In fact, they have the potential to treat nerve injury-induced pain that usually doesn’t respond to exogenous opioids such as morphine and its derivatives, according to Jianguo Cheng, MD, PhD, principal investigator of the Department of Defense (DOD)-funded study and Professor and Director of Cleveland Clinic’s Pain Medicine Fellowship Program.

Dr. Cheng and his collaborator, Tingyu Qu, MD, PhD, from the University of Illinois at Chicago, developed the patent-pending technology to differentiate the autologous stem cells into chromaffin-like cells. Initial animal studies have already demonstrated the feasibility of transplanting the cells for pain relief.

The current DOD study in rats is testing safety, analgesic effects and anti-tolerance effects, as well as the longevity and stability of the cells once transplanted. “While many more studies will be needed over many years before this approach can be tested in humans, initial results from animal studies have shown great promise,” says Dr. Cheng. In addition to patients with intractable neuropathic pain, patients with cancer pain could someday be good candidates for this type of therapy, he adds.

Potential Advantages Are Many

If the stem cell therapy is found to be safe and effective, potential advantages include:

  • Therapeutic alternative — This approach promises the ability to treat intractable neuropathic pain in patients who don’t respond to prescription opioids.
  • Fewer side effects — Patients who opt for analgesic cell therapy could avoid the side effects of exogenous opioids, such as respiratory depression, immune system compromise, disruption or depression of endocrine functions, constipation, vomiting and itching.
  • Decreased abuse — Endogenous opioids from analgesic cell therapy serve as an alternative to highly addictive prescription opioids, which cause more deaths than car accidents and are often diverted for illegal use.
  • Reprogrammed stem cells — Unlike embryonic stem cells, once the mesenchymal stem cells are differentiated into chromaffin-like cells, they can’t grow or divide, so tumor risk is not an issue.

If this analgesic cell therapy is found to be viable, it has the potential to be a clinical game-changer. As stated in the DOD’s assessment of the grant application: “This approach to pain management is very innovative and, if successful, could have a tremendous impact on the way that chronic pain is treated.”

Save the Date: Cleveland Clinic’s Annual Pain Management Symposium Comes to Las Vegas in February 2014

More than 250 physicians and other providers from 40 states and 12 nations brought themselves up to date on the full spectrum of pain medicine at Cleveland Clinic’s 15th Annual Pain Management Symposium, held in Sarasota, Fla., this past February.

Now course organizers are busy planning for the 16th Annual Pain Management Symposium, to be held Feb. 15-19, 2014, at Caesar’s Palace in Las Vegas.

The comprehensive five-day course provides in-depth reviews and analyses of most major aspects of contemporary pain medicine. This year’s topic categories ranged from emerging technologies to controversies in pain medicine and from evidence-based spine pain care to risk management in pain medicine. Additional program sections were devoted to imaging techniques and updates on headache management.

“This course tackles the provocative issues in pain medicine and challenges attendees to examine the basis for their medical decisions,” says Richard Rosenquist, MD, Chairman of Cleveland Clinic’s Department of Pain Management and one of the faculty members for this year’s symposium.

Content is presented by approximately 40 renowned experts in pain management. About half the faculty comes from Cleveland Clinic and half from other leading U.S. and international medical centers. This year’s faculty included experts from Sweden and the United Kingdom. The agenda is a diverse mix of traditional lectures with problem-based learning discussions, cadaver workshops on novel interventional techniques, and live model workshops for training in ultrasonography-guided injections and peripheral nerve blocks.

While many attendees are specialists in anesthesiology or pain management, attendees this year came from nearly 20 different specialties, with sizable contingents from rehabilitation medicine, internal medicine and family practice. The course is designated for CME credit for physicians and CE credit for nurses.

“Plan to attend the 2014 Pain Management Symposium to learn about the latest advances in pain medicine and how healthcare reform is changing our practices,” advises Dr. Rosenquist.

For details and registration information on the 2014 symposium, email or visit later this year.