Ambroxol: A Potential New Treatment for Chronic Pain

By A Rahman Ford, PNN Columnist

Researchers say a drug long used in cough syrup and cold medicines shows potential for treating some types of neuropathic pain.

A small study recently published in the journal Headache found that topical administration of ambroxol in a cream could significantly decrease pain in patients with trigeminal neuralgia, a chronic facial condition that can make even routine tasks such as brushing one’s teeth excruciatingly painful. 

In their review of the medical records of five trigeminal neuralgia patients, German researchers reported that all five patients experienced pain reduction with ambroxol 20% cream being applied within 30 minutes of a pain flare, with pain relief lasting from 4 to 6 hours.  In one case, pain was eliminated completely in one week.  

The results were similar to those of previous German studies and were so significant that researchers recommended that ambroxol “should be investigated further as a matter of urgency.”

Similarly, a recent study in the journal Pain Management found that application of topical ambroxol reduced spontaneous pain in several patients with complex regional pain syndrome (CRPS), a little understood nerve condition that causes chronic pain after a significant injury or surgery.  Notably, ambroxol therapy improved several other neuropathy-related conditions in CRPS patients, including edema, allodynia, hyperalgesia, skin reddening, motor dysfunction and skin temperature.

An Old Drug with a New Purpose

With a pharmacological history that can be traced back to Indian ayurvedic medicine, ambroxol was initially approved in 1978 as a medication to break down mucus and make it easier to eliminate by coughing.  It is generally administered in tablet or syrup form. 

Ambroxol is also used to treat a sore throat associated with pharyngitis, thus its potential role as a potent local anesthetic.  The drug’s anesthetic properties stem from its ability to block sodium and calcium channels that transmit pain signals.

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Although the idea that ambroxol can treat a sore throat is widely accepted, its application to other forms of pain is more recent.  

Previous studies using animal models of neuropathic pain have been promising.  In a 2005 study, researchers effectively reduced – and in some cases eliminated – chronic neuropathic and inflammatory pain in rats. Indian researchers also found ambroxol effective in treating neuropathic pain in rats, attributing its success to its antioxidative and anti-inflammatory properties.  Unfortunately, human studies are few at this point.

Ambroxol and Fibromyalgia

A 2017 Clinical Rheumatology study showed that ambroxol can play a key role in treating chronic pain associated with fibromyalgia.  As reported by Fibromyalgia News Today, researchers from Mexico added ambroxol to the treatment regimens of 25 fibromyalgia patients, three times a day for one month.  At the end of the study, pain scores decreased significantly and there was also noticeable improvement in sleep disturbances, stiffness and autonomic nervous system dysfunction.  No major adverse events were reported. 

Another 2017 study supported these findings, with the authors concluding that “fibromyalgia treatment with ambroxol should be systematically investigated” because the drug “is the only treatment option used thus far that has the potential to address not just individual but all of the aforementioned aspects of pain.”

Although data on its effectiveness in humans are limited, ambroxol shows great potential in treating painful conditions for which there are currently few safe and effective options.  It is particularly attractive because it has few significant side effects, is not addictive and can be administered topically in some instances.

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A. Rahman Ford, PhD, is a lawyer and research professional. He is a graduate of Rutgers University and the Howard University School of Law, where he served as Editor-in-Chief of the Howard Law Journal. He earned his PhD at the University of Pennsylvania.

Rahman lives with chronic inflammation in his digestive tract and is unable to eat solid food.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represent the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Experimental Stem Cell Therapy Reverses MS

By Steve Weakley

A small but promising study has shown that an experimental stem cell therapy can dramatically slow the progression of multiple sclerosis. Some MS patients treated with their own stem cells even experienced a reversal of their symptoms that has lasted for years.

MS is a chronic, incurable and progressive disease that attacks the body’s central nervous system, causing numbness in the limbs, difficulty walking, paralysis, loss of vision, fatigue and pain. The disease affects over 2 million people around the world.

An international team of researchers enrolled 110 patients in the study with relapsing-remitting MS, a version of the disease where symptoms appear for a few days or weeks, followed by periods of remission.

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Half of the patients were treated with standard MS medications as a control group, while the other half went through a four-step experimental procedure.

The experimental group was given chemotherapy to stimulate the production of hematopoietic stem cells that recharge the immune system. Those stem cells were then removed from the patients’ blood and frozen.  After that, a more powerful round of chemotherapy was used to wipe out the patients’ damaged immune systems, and the thawed stem cells were put back into their bodies by transfusion.

Over half of the 55 patients in the control group continued to see their disease progress, while only three patients got worse in the experimental stem cell group. The other 52 had fewer symptoms and a better quality of life. The findings were reported in the journal JAMA.

“It’s the best evidence comparing stem cell transplants to standard therapy,” Harry Atkins, MD, a stem cell scientist at Ottawa Hospital in Canada told Vox . “This is one of the first pieces of proof that, yes, patients who have aggressive MS do better after a transplant than with the standard therapy.”

“The stem cell therapy gets patients off lifelong treatments and gives them results that have never been seen before with this disease,” said lead author Richard Burt, MD, a stem cell researcher and physician at Northwestern University.

One of Burt’s patients who benefited from the stem cell transplant is 28-year old Amanda Loy, who told Vox that prior to treatment she needed a cane to walk and was unable to work.  Within a year of treatment her symptoms had disappeared.

“It sounds so dramatic, but (the treatment) gave me my life back,” said Loy, who now works as a full-time teacher, runs half marathons and plays soccer with her 10-year-old son. She no longer takes MS medication.

Researchers still don’t know if the stem cell therapy will work with other forms of MS or how long the benefits will last. But it’s the first treatment that has shown the potential to actually reverse the disease.

“I do think it’s going to change the natural history of MS,” says Burt. “When you use it in the right group of patients with MS, you get these really gratifying results.”

A recent study by Australian researchers found that another experimental stem cell therapy shows promise in treating patients with progressive multiple MS, the most difficult-to-treat form of the disease.

Scientists at the University of Queensland extracted immune cells from patients who had either primary or secondary progressive MS. The cells – known as T-cells – were then “trained” in a laboratory to target and kill cells infected with the Epstein Barr virus, which has long been associated with MS.

When the altered T-cells were injected back into the bloodstream of 10 patients, seven said their symptoms improved. They had more energy, improved concentration, slept better, and had improved vision and balance. There were no serious side effects.

Scrambler Therapy Helped My Daughter Walk Again

By Reggie Greening, Guest Columnist

Beginning in August 2017, my daughter Amanda began having severe pain in her left foot after spraining her ankle. She was 20 years old at the time and described the pain as feeling as though her bones were being crushed by a red-hot anvil.

Over the next few months, Amanda started having more and more symptoms. It began with sharp pain, then discoloration, and severe swelling set in. This was about the time when she stopped being able to walk and had to be put on opioid medication in an attempt to manage the pain.

The bone crushing sensation began around the end of September, followed closely by burning pain. Amanda was still unable to walk and was taking opioids every four to six hours like clockwork. No one could figure out what was wrong or how to manage the pain other than with opioids.

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While attempting to get a diagnosis, Amanda went through many rounds of testing. She had multiple x-rays, two MRIs (one with contrast dye injected intravenously), a three-phase bone scan, a nerve conductivity test, and two phases of bloodwork examined. She also went to a plethora of doctors, including a podiatrist, orthopedist, rheumatologist, dermatologist, physical therapists, homeopathic physician, chiropractor, pain management doctor, and a general medicine doctor.

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The podiatrist and one of her physical therapists suspected Complex Regional Pain Syndrome (CRPS), and her podiatrist was the one who eventually determined the diagnosis of CRPS on February 16, 2018.

This spurred my research to find a more sustainable treatment option for Amanda. I spent hours searching online before discovering Scrambler Therapy.

I found a physician in New Jersey who posted videos on YouTube about Scrambler Therapy (also known as Calmare Pain Relief Therapy) and its benefits for those suffering with CRPS and other chronic nerve conditions.

We live in Louisiana, so I looked for a doctor who had a Scrambler Therapy machine closer to our home state. I eventually found a doctor in Dallas who has a machine in his office.

Amanda’s first round of treatment was administered by an osteopathic doctor in March 2018. After the fourth consecutive day of treatment, she was able to walk with the aid of crutches for the first time in seven months. The next day, after her fifth treatment, Amanda was able to walk independently. By the end of her initial round of treatment, she was entirely off opioids and NSAID pain relievers.

Our local TV station did a story about Amanda’s recovery.

Right now, the Scrambler treatment is not covered by insurance and payment for it adds up rather quickly. I am trying to get this therapy more widely acknowledged and known about so that it may become an option for others suffering with chronic neuropathic pain.

I have seen the benefits of Scrambler Therapy firsthand in my daughter. At the time of this writing, Amanda has been off opioids for two months and has been able to maintain the benefits of the initial treatment through booster treatments as needed.

Scrambler Therapy has the potential to help not just those suffering from CRPS (for whom pain relief often seems distant and hopeless), but also for those suffering from other neuropathic pain conditions.

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The Greening family lives in Shreveport, Louisiana.

Pain News Network invites other readers to share their stories with us. Send them to editor@painnewsnetwork.org.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.

Can Gabapentin Improve Your Sex Life?

By Pat Anson, PNN Editor

Over the years the nerve drug gabapentin (Neurontin) has been used to treat a cornucopia of chronic pain conditions, from fibromyalgia and diabetic neuropathy to hot flashes and shingles.

Gabapentin is so widely prescribed that a Pfizer executive once called the drug “the snake oil of the twentieth century” because researchers found it successful in treating just about everything they studied.

Add sexual function to the list.

In a small study, researchers at Rutgers University found that gabapentin improved sexual desire, arousal and satisfaction in 89 women with provoked vulvodynia, a chronic condition characterized by stinging, burning and itching at the entry to the vagina. Vulvar pain often occurs during intercourse, which leads to loss of interest in sex.

The improvements in desire, arousal and sexual satisfaction were small, but considered “statistically significant” in research parlance. Gabapentin did not improve lubrication or orgasm.

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"Our theory was that reducing pelvic floor muscle pain might reduce vulvodynia pain overall and thus improve sexual function," said Gloria Bachmann, MD, director of the Women's Health Institute at Rutgers and lead author of the study published in the Journal of Obstetrics and Gynecology.

"We found that women with greater muscle pain responded better in terms of pain and improved arousal than those with less pain, which suggests that Gabapentin be considered for treatment in women who have significant muscle tightness and spasm in the pelvic region.”

Does this mean gabapentin is a female version of Viagra? Not necessarily, says Bachmann, who stressed that the study only focused on women with vulvodynia.

“We didn't research the question of gabapentin enhancing sexual function in all women,” Bachmann wrote in an email to PNN. “The decision to give gabapentin to a woman who reports chronic vulvar pain and sexual dysfunction would have to be made on an individual basis, depending on her medical history and the results of her physical and pelvic examination.

“From the data, it appears that women with increased muscle tenderness of the pelvic floor may be the group who benefit most from gabapentin.”

Sales of gabapentin have soared in recent years — not because it improves sexual satisfaction — but because it is seen as a safer pain reliever than opioid medication.

Patients prescribed gabapentin often complain of side effects such as mood swings, depression, dizziness, fatigue and drowsiness.  Drug abusers have also discovered that gabapentin can heighten the effects of heroin, cocaine and other illicit substances, and it is increasingly being abused.

Gene Therapy Eases Chronic Pain in Dogs

By Lisa Marshall, University of Colorado at Boulder

When Shane the therapy dog was hit by a Jeep, life changed for him and his guardian, Taryn Sargent.

The impact tore through the cartilage of Shane's left shoulder. Arthritis and scar tissue set in. Despite surgery, acupuncture and several medications, he transformed from a vibrant border collie who kept watch over Sargent on long walks to a fragile pet who needed extensive care.

"Sometimes he would just stop walking and I'd have to carry him home," recalls Sargent, who has epilepsy and relies on her walks with Shane to help keep her seizures under control. "It was a struggle to see him in that much pain."

Today, 10-year-old Shane's pain and reliance on medication have been dramatically reduced and he's bounding around like a puppy again, 18 months after receiving a single shot of an experimental gene-therapy invented by CU Boulder neuroscientist Linda Watkins

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shane and taryn sargent (casey cass/cu boulder)

Thus far, the opioid-free, long-lasting immune modulator known as XT-150 has been tested in more than 40 Colorado dogs with impressive results and no adverse effects. With human clinical trials now underway in Australia and California, Watkins is hopeful the treatment could someday play a role in addressing the nation's chronic pain epidemic.

"I'm hoping the impact on pets, their guardians and people with chronic pain could be significant," said Watkins, who has worked more than 30 years to bring her idea to fruition. "It's been a long time coming."

The Role of Glial Cells

Watkins' journey began in the 1980s when, as a new hire in the department of psychology and neuroscience, she began to rock the boat in the field of pain research.

Conventional wisdom held that neurons were the key messengers for pain, so most medications targeted them. But Watkins proposed that then-little-understood cells called "glial cells" might be a culprit in chronic pain. Glial cells are immune cells in the brain and spinal cord that make people ache when they're sick. Most of the time, that function protects us. 

Watkins proposed that in the case of chronic pain, which can sometimes persist long after the initial injury has healed, that ancient survival circuitry somehow gets stuck in overdrive. She was greeted with skepticism.

"The whole field was like 'what on Earth is she talking about?'"

She and her students hunkered down in the lab nonetheless, ultimately discovering that activated glial cells produce specific inflammatory compounds which drive pain. They also learned that, after the initial sickness or injury fades, the cells typically produce a compound called Interleukin 10 (IL-10) to dampen the process they started.

"IL-10 is Mother Nature's anti-inflammatory," she explains. "But in the onslaught of multiple inflammatory compounds in chronic pain, IL-10's dampening cannot keep pace."

Over the years, she and her team experimented with a host of different strategies to boost IL-10. They persisted and, in 2009, Watkins co-founded Xalud Therapeutics. Their flagship technology is an injection, either into the fluid-filled space around the spinal cord or the site of an inflamed joint, that delivers circles of DNA in a sugar/saline solution to cells, instructing them to ramp up IL-10 production.

With financial help from the National Institute of Neurological Disorders and Stroke, the MayDay Fund and CU's Technology Transfer Office – which has provided intellectual property support, assistance with licensing agreements, and help obtaining a $100,000 research grant in 2018 – Watkins is edging closer to bringing her idea to clinical practice.

She has teamed up with veterinary chronic pain specialist Rob Landry, owner of the Colorado Center for Animal Pain Management in Westminster, to launch the IL-10 research study in dogs.

Their results have not been published yet. But thus far, the researchers say, the results look highly promising.

"They're happier, more engaged, more active and they're playing again," said Landry, as he knelt down to scratch Shane's belly after giving him a clean bill of health.

With Shane able to accompany her on her walks again, Sargent has also seen her quality of life improve. Her seizures, which increased in frequency when Shane was injured, have subsided again.

linda watkins with shane (casey cass/cu boulder)

linda watkins with shane (casey cass/cu boulder)

Human Studies Underway

Because the treatment is so localized and prompts the body's own pain-killing response, it lacks the myriad side effects associated with opioids – including constipation and dependency – and it can last for many months after a single injection.

Ultimately, that could make it an attractive option for people with neuropathic pain or arthritis, Watkins says.

This summer, Xalud Therapeutics launched the first human study in Australia, to test the safety, tolerability and efficacy of the compound. Another one-year clinical trial of 32 patients with osteoarthritis of the knee is now underway in Napa, California.

More research is necessary in both pets and people, Watkins stresses. But she's hopeful.

"If all goes well, this could be a game-changer."

Feds Funding Study of Cannabis as Opioid Alternative

By Pat Anson, PNN Editor

Columbia University has been awarded a grant from the National Institute on Drug Abuse (NIDA) to investigate whether medical cannabis can reduce the use of opioids and overdose risk in chronic pain patients.  

The grant was awarded after researchers with Columbia Care completed a small pilot study that found nearly two-thirds of patients with chronic nerve pain were able to reduce or stop their opioid use. Columbia Care is a private medical marijuana company not affiliated with the university that operates a chain of cannabis dispensaries around the country.

“There is an urgent need to investigate the potential impact of cannabinoid use on limiting opioid overdose risk and to determine whether specific products are more beneficial for certain populations of patients with pain and opioid use,” said Arthur Robin Williams, MD, a professor in the Division on Substance Use Disorders in the Columbia University Department of Psychiatry.

The pilot study involved 76 neuropathy patients in New York State who were given Columbia Care’s dose-metered cannabis products for nine months. By the end of the study, 62 percent of the patients were able to reduce or stop using opioid pain medication.

Columbia Care makes a variety of medical cannabis products that come in tablets, tinctures, suppositories, topical formulations or can be used in vaporizers. 

“We have seen through this pilot study the power of our proprietary formulations to reduce our patients’ dependence on opioids in a defensible, scientific manner,” said Rosemary Mazanet, MD, chief science officer and chair of the scientific advisory board at Columbia Care.

DRUG POLICY ALLIANCE

DRUG POLICY ALLIANCE

Although medical marijuana is often touted as a possible solution to the nation’s opioid crisis, research findings so far have been mixed.

A recent study by the RAND Corporation found little evidence that states with medical marijuana laws see reductions in legally prescribed opioids. While some pain patients may be using or experimenting with medical marijuana, RAND researchers do not believe they represent a significant part of the opioid analgesic market.

"If anything, states that adopt medical marijuana laws... experience a relative increase in the legal distribution of prescription opioids,” researchers found.

Another study of Medicare and Medicaid patients found that prescriptions for morphine, hydrocodone and fentanyl dropped in states with medical marijuana laws, while daily doses for oxycodone increased. A second study found a 6% decline in opioid prescribing to Medicaid patients in states with medical marijuana laws.  Both studies were conducted during a period when nationwide opioid prescribing was already in decline.

A 2014 study published in JAMA Internal Medicine found that opioid overdoses declined by nearly 25 percent in states where medical marijuana was legalized.

New Lyme Disease Test Could Lead to Earlier Treatment

By Pat Anson, PNN Editor

At long last, scientists are close to developing a new test to detect Lyme disease weeks sooner than current tests -- allowing patients to begin treatment earlier.

Lyme disease is a bacterial illness spread by ticks. Left untreated, it can lead to chronic conditions such as joint and back pain, chronic fatigue, fibromyalgia and neuropathy.

Borrelia burgdorferi was first identified as the bacteria that causes Lyme disease in 1983.  The antibody tests currently used to detect Borrelia were developed a decade later and have a number of shortcomings. They can take up to three weeks to get results and cannot distinguish between an active infection or an old one.

A team of scientists recently reported in the journal Clinical Infectious Diseases that advances in molecular diagnostics should make a new DNA test for Borrelia technically feasible.

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“These direct tests are needed because you can get Lyme disease more than once, features are often non-diagnostic and the current standard FDA-approved tests cannot distinguish an active, ongoing infection from a past cured one,” said lead author Steven Schutzer, MD, a physician-scientist at Rutgers New Jersey Medical School.

“The problem is worsening because Lyme disease has increased in numbers to 300,000 per year in the United States and is spreading across the country and world.”

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Early symptoms of Lyme disease include fever, chills, headaches, fatigue, muscle and joint aches, and swollen lymph nodes. A delayed rash often appears at the site of the tick bite, which resembles a ring or bulls-eye. When there is no rash, a reliable laboratory test is needed to detect an active disease.

“The new tests that directly detect the Lyme agent’s DNA are more exact and are not susceptible to the same false-positive results and uncertainties associated with current FDA-approved indirect tests,” said Schutzer.

Lyme disease is usually treated with antibiotics, but some patients experience complications that lead to Lyme disease syndrome (PTLDS), with long-term symptoms such as fatigue, muscle and joint pain and cognitive issues. Autoimmune diseases have also been associated with chronic Lyme disease.