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Pain Management by Ozone

Dr (Maj) Pankaj N Surange
MBBS, MD, FIP
Interventional pain and spine specialist
09871985514

Ozone may be a wonder molecule to the clinicians though its potentials yet to be fully explored. It has role in controlling bacterial, fungal & viral infections including AIDS, treating non-healing ulcers, Rheumatoid and other kinds of arthritis, different kind of skin diseases and many others.

What is ozone?

Ozone is a tri-atomic Oxygen molecule, O3, with a different molecular structure than Oxygen. Its name is derived from the Greek word ozein meaning “to smell”. At room temperature, Ozone is a colorless gas with a characteristic odor (similar smell after thunderstorms, at high altitudes or near the sea etc). At ground level its concentration 0.03 - 0.04 ppm. Ozone in the atmosphere is produced by action of UV rays and thunderstorm on the atmospheric Oxygen; but Medical Ozone is produced from pure medical grade oxygen with the help of high voltage electrical discharge. Medical ozone is a mixture of oxygen and ozone of different concentration. Medical ozone is always freshly prepared on site (in a special generator) for immediate administration. A trained physician according to the medical indication and the patient’s condition determines the exact dose of ozone.

Safety and efficacy of Ozone therapy

Treating patients with ozone is not a new procedure. The first ozone generators were developed by Werner von Siemens in Germany in 1857, and 1870 saw the first report on ozone being used therapeutically to purify blood, by C. Lender in Germany.
During World War 1, ozone was used to treat wounds, trench foot, gangrene and the effects of poison gas. Dr. Albert Wolff of Berlin also used ozone for colon cancer, cervical cancer and decubitus ulcers in 1915. Today, after 125 years of usage, ozone therapy is a recognized modality in many nations: Germany, France, Italy, Russia, Romania, Czech Republic, Poland, Hungary, Bulgaria, Israel, Cuba, Japan, Mexico, and in five US states. It was also used extensively to treat war wounds during World War-II.
It was not popularized before, as ozone resistant materials were not used to produce ozone generators. Also the exact concentration of ozone was unknown. Former Ozone generators are either UV light Ozone generators or plasma type Ozone generators. Here, it was very difficult to know the precise concentration of ozone. Now with the present Corona-discharge Ozone generators, it is possible to know the exact concentration of Ozone. Also, by changing the current or the oxygen flow, Ozone concentration can be precisely modified.
Ozone has been found to be an extremely safe medical therapy, free from side effects. In a 1980 study done by the German Medical Society for Ozone Therapy, 644 therapists were polled regarding their 384,775 patients, comprising a total of 5,579,238 ozone treatments administered. There were only 40 cases of side effects noted out of this number that represents the incredibly low rate of .000007%. Ozone Therapy has been described as the safest known medical therapy.

Indications of Ozone therapy

Among the various diseases presented with pain the following has been treated with very good results; e.g. rheumatoid arthritis, systemic lupus erythemoatosis, scleroderma, polymyositis/fibromyositis, ankylosing spondylitis, osteo-arthritis, Reiter syndrome, psoriasis, synovitis, gout, chrondrocalcinosis, pyrophosphate arthropathy, calcific peri-arthritis, calcific tendinitis, calcinosis and inter-vertebral disc prolapse. In my Pain Clinic I have been treating osteo-arthritis of knee, trigger point injections for fibromyalgia/ Myofascial pain, and inter-vertebral disc prolapse or slipped disc successfully.

How Ozone should be administered?

There are different methods like injections of ozone/oxygen mixture; insufflations through rectum; treating with ozonated water (drinking, dressing wound/ulcers etc.); auto-transfusion of ozonated blood, application of ozonated oil and so on depending on type and site of disease. But for treatment of different pain we use injection of different concentrations of ozone gas only. Ozone molecule is not stable. It has a half-life of 20 minutes only. So, within 20 minutes only half of the original ozone remains, the rest becomes oxygen. Increase in temperature decreases its half-life. For injection it is always freshly prepared on site for immediate administration. Only Ozone resistant syringes can be used for injecting it. The contraindications for treatment with ozone are only a few. They are active bleeding from any site, pregnancy, and active hyperthyroidism.

Mechanism of action

The mechanisms of action of ozone are many. Most of its actions are due to the active oxygen atom liberated from breaking down of ozone molecule. Besides its action as bactericidal, fungicidal, viricidal agent, it activates cellular metabolism, modulates the immune system & increases and activates body's own antioxidants and radical scavengers. In the treatment of pain different other mechanism acts. There is enhancement of circulation. Ozone reduces or eliminates clumping and red cell. Its flexibility is restored, along with oxygen carrying ability (due to the stimulation of 2,3-diphosphoglycerate). Oxygenation of the tissues increases as the arterial partial pressure increases and viscosity decreases. Ozone also oxidizes the plaque in arteries, allowing the removal of the breakdown products, unclogging the blood vessels. All these leads to an increase in the amount of oxygen released to the diseased tissues. There is also reduced formation of inflammatory mediators like different prostaglandins and so there is an anti-inflammatory action.

Ozone in PIVD/Slipped disc

In case of prolapsed inter-vertebral disc (or, slipped disc) different other mechanism acts. Inter-vertebral disc is filled with nucleus pulposus which is a jelly like material which holds water (90% of disc material is water). When ozone is injected into the disc the proteo-glycan bridges in the jelly-like material are broken down and they no longer capable of holding water. As a result disc shrinks and mummified which is equivalent to surgical discectomy and so the procedure is called ozone discectomy or ozonucleolysis. It has been published in ANESTHESIA AND PAIN journals that up to 85% of disc operation can be avoided with these non-surgical interventions. Success rate is about 88% which is comparable to surgical discectomy (50% to 90%). Complications are remarkably low and much less than surgery.

Future

Ozone is gradually gaining popularity in various medical fields especially in pain management. Newer modification in techniques and administration of ozone, more and more publication of scientific materials in the medical journals and animal studies have made it more acceptable to the medical community and gradually it is becoming more popular.

Understanding cancer pain
Dr (Maj) Pankaj N Surange

Introduction
When you or a loved one receives a diagnosis of cancer, it isn't long before you begin to think of the pain many people associate with cancer. It can be a frightening time. What will the pain be like? What will it do to our lives? Many people with cancer eventually experience pain due to their condition. Approximately twenty percent of patients with newly diagnosed malignancies complain of pain. Thirty percent of patients undergoing cancer treatment complain of pain, and up to ninety percent of those with advanced cancer experience pain (Grossman 1994).
Pain associated with cancer can take many forms and is experienced differently by each patient. Pain can be sharp and severe, or it can be a dull constant ache. Regardless of the type of pain, a diagnosis of cancer does not mean you have to suffer with debilitating pain.
Today, most concerns about cancer-related pain can be relieved by understanding the facts about cancer pain, and learning about the help that is available for pain relief.
How pain happens?
Pain is transmitted through the body by the nervous system when our nerve endings detect damage to a part of the body. The nerves transmit the warning through defined nerve pathways to the brain, where the signals are interpreted as pain. Sometimes pain results when the nerve pathways themselves are injured. You feel pain when your brain receives the signal from your nerves that damage is occurring. All types of pain are transmitted this way, including cancer pain.
Pain can be acute or chronic: Acute pain usually starts suddenly, may be sharp, and often triggers visible bodily reactions such as sweating, an elevated blood pressure, and more. Acute pain is generally a signal of rapid-onset injury to the body, and it resolves when pain relief is given and/or the injury is treated.
Chronic pain lasts, and pain is considered chronic when it lasts beyond the normal time expected for an injury to heal or an illness to resolve. Chronic pain, sometimes called persistent pain, can be very stressful for both the body and the soul, and requires careful, ongoing attention to be appropriately treated.
Along with chronic cancer pain, sometimes people have acute flares of pain when not all pain is controlled by the medication or therapy. This pain, usually called breakthrough pain, can also be controlled by medications.
Cancer pain can be caused by many different sources. Pain can be experienced when a tumor presses on nerves or
expands inside a hollow organ. Pain also commonly originates from bone destructive lytic lesions. Bone marrow infiltration commonly cause bone pain that can be severe. Unfortunately, the radiation and chemotherapeutic treatments that are frequently used to treat cancer can also cause pain.
Assessment of your pain
The first step in getting your pain under control is talking honestly about it.
This means telling them:
• Where you have pain
• What it feels like (sharp, dull, throbbing, constant, burning, or shooting)
• How strong your pain is
• How long it lasts
• What lessens your pain or makes it worse
• When it happens (what time of day, what you're doing, and what's going on)
• If it gets in the way of daily activities
Your pain physician may ask you to describe your pain in a number of ways. A pain scale is the most common way. The scale uses the numbers 0 to 10, where 0 is no pain, and 10 is the worst. You can also use words to describe pain, like pinching, stinging, or aching. Some doctors show their patients a series of faces and ask them to point to the face that best describes how they feel.

Your Pain Control Plan
Only you know how much pain you have. Telling your doctor and nurse when you have pain is important. Not only is pain easier to treat when you first have it, but pain can be an early warning sign of the side effects of the cancer or the cancer treatment. You have a right to pain relief, and you should insist on it.
Cancer pain can almost always be relieved.
There are many different medicines and interventions available to control cancer pain. You should expect your doctor to seek all the information and resources necessary to make you as comfortable as possible. However, no one doctor can know everything about all medical problems. If you are in pain and your oncologist suggests no other options, ask to see a pain specialist or have your doctor consult with a pain specialist.
Controlling your cancer pain is part of the overall treatment for cancer.
Your pain physician wants and needs to hear about what works and what doesn’t work for your pain. Knowing about the pain will help your doctor better understand how the cancer and the treatment are affecting your body.
Preventing pain from starting or getting worse is the best way to control it.
Pain is best relieved when treated early. You may hear some people refer to this as “staying on top” of the pain. Do not try to hold off as long as possible between doses. Pain may get worse if you wait, and it may take longer, or require larger doses, for your medicine to give you relief.
You have a right to ask for pain relief.
Not everyone feels pain in the same way. There is no need to be “stoic” or “brave” if you have more pain than others with the same kind of cancer. In fact, as soon as you have any pain you should speak up.
People who take cancer pain medicines, as prescribed by the doctor, rarely become addicted to them.
Addiction is a common fear of people taking pain medicine. Such fear may prevent people from taking the medicine. Or it may cause family members to encourage you to “hold off” as long as possible between doses. Addiction is defined by many medical societies as uncontrollable drug craving, seeking, and use. When opioids (also known as narcotics) — the strongest pain relievers available — are taken for pain, they rarely cause addiction as defined here. When you are ready to stop taking opioids, your pain physician gradually lowers the amount of medicine you are taking. By the time you stop using it completely, the body has had time to adjust.
Treatment options
There is more than one way to treat pain. A simple, well-validated and effective method for assuring the rational titration of therapy for cancer pain has been devised by WHO. It has been shown to be effective in relieving pain for approximately 90 percent of patients with cancer and over 75 percent of cancer patients who are terminally ill. The World Health Organization (WHO) in 1986 established a stepladder approach for treatment of patients with cancer pain (fig.). The goal for this ladder was to provide treatment guidelines that healthcare practitioners could easily follow. The five essential concepts in the WHO approach to drug therapy of cancer pain are:
i) By the mouth. ii) By the clock. iii) By the ladder. iv) For the individual.
v) With attention to detail.
Medicines
Non opioids
Opioids
Adjuvants

Medicines are prescribed based on the kind of pain you have and how severe it is. In studies, these medicines have been shown to help control cancer pain. Doctors use three main groups of drugs for pain: nonopioids, opioids, and other types
1. Nonopioids - for mild to moderate pain
Nonopioids are drugs used to treat mild to moderate pain, fever, and swelling. On a scale of 0 to 10, a nonopioid may be used if you rate your pain from 1 to 4. These medicines are stronger than most people realize. In many cases, they are all you'll need to relieve your pain. You just need to be sure to take them regularly.
You can buy most nonopioids without a prescription. But you still need to talk with your doctor before taking them. Some of them may have things added to them that you need to know about. And they do have side effects. Common ones, such as nausea, itching, or drowsiness, usually go away after a few days.
2. Opioids - for moderate to severe pain
If you're having moderate to severe pain, your doctor may recommend that you take stronger drugs called opioids. Opioids are also known as narcotics. You must have a doctor's prescription to take them. They are often taken with aspirin, ibuprofen, and acetaminophen. Getting relief with opioids
Over time, people who take opioids for pain sometimes find that they need to take larger doses to get relief. This is caused by more pain, the cancer getting worse, or medicine tolerance (see Medicine Tolerance and Addiction). When a medicine doesn't give you enough pain relief, your doctor may increase the dose and how often you take it. He or she can also prescribe a stronger drug. Both methods are safe and effective under your doctor's care. Do not increase the dose of medicine on your own.
3.Adjuvants
They can be used along with nonopioids and opioids. Some include:
Antidepressants. Some drugs can be used for more than one purpose. For example, antidepressants are used to treat depression, but they may also help relieve tingling and burning pain. Nerve damage from radiation, surgery, or chemotherapy can cause this type of pain.
Antiseizure medicines (anticonvulsants). Like antidepressants, anticonvulsants or antiseizure drugs can also be used to help control tingling or burning from nerve injury.
Steroids . Steroids are mainly used to treat pain caused by inflammation (swelling.)
Interventions
While opioids are the mainstay of cancer pain management, they have their limitations. Some patients may only tolerate moderate doses of opioids, manifesting side-effects such as sedation, confusion, and constipation. Another reason for opioid ineffectiveness may be the development of opioid-resistant pain. For these reasons, the search for analgesia has resulted in introduction of Interventions as fourth step in WHO’s ladder for chronic and cancer Pain management. A wide array of procedures exists (e.g., local anesthetic/steroid deposition, neurolysis by chemical or thermal means, or the implantation of spinal pumps to deliver medications not effective by the oral/transcutaneous route)
Sympathetic Blockade:- The sympathetic chain exists along the vertebral column, carries much nociceptive information, so blockade of sympathetic ganglia may improve visceral pain as well as sympathetically mediated pain. This may be considered an attractive and simple option for the diagnosis of pain and possible long-term pain relief.
Spinal Analgesia.:- Opioids, local anesthetics, spasmolytics, and alpha-2 agonists to both subarachnoid and epidural routes of administration. To provide chronic treatment, tunneled subcutaneous catheters are commonly connected to pumps with reservoirs.
Spinal Cord Stimulation:- The mechanism of analgesia produced by spinal cord stimulation (SCS) is still unclear. Some hypotheses involve antidromic activation of A-beta afferents (“gate control” theory), activation of central inhibitory mechanisms, increase in substance-P release, and actual block of transmission of electrochemical information anywhere in the dorsal spinothalamic tract. The attractiveness of SCS lies in the potential to provide analgesia to severe neuropathic states without the need for medication. Patients control the stimulation (on/off and intensity) with a small battery-operated control. SCS has a low incidence of infection since it is not accessed except for a battery change, which may be needed every 2 to 4 years, depending on the level and frequency of stimulation.
Neurolysis :- Injections of neurolytic agents to destroy nervesand interrupt pain pathways have been used for manyyears. Neurolysis is indicated inpatients with severe, intractable pain in whom lessaggressive maneuvers are ineffective or intolerable because of either poor physical condition or the development of side effects.
Managing and preventing side effects
Some pain medicines may cause:
Constipation (trouble passing stools) Opioids cause constipation to some degree in most people. Opioids cause the stool to move more slowly along the intestinal tract, thus allowing more time for water to be absorbed by the body. The stool then becomes hard. Constipation can often be prevented and/or controlled.
Drowsiness (feeling sleepy) At first, opioids cause drowsiness in some people, but this usually goes away after a few days. If your pain has kept you from sleeping, you may sleep more for a few days after beginning to take opioids while you “catch up” on your sleep. Drowsiness will also lessen as your body gets used to the medicine.
Nausea (upset stomach) and Vomiting (throwing up) Nausea and vomiting caused by opioids will usually disappear after a few days of taking the medicine. Some people think they are allergic to opioids if they cause nausea. Nausea and vomiting alone usually are not allergic responses. But a rash or itching along with nausea and vomiting may be an allergic reaction. If this occurs, stop taking the medicine and tell your doctor at once.
Medicine Tolerance and Addiction
When treating cancer pain, addiction is rarely a problem. Addiction is when people can't control their seeking or craving for something. They continue to do something even when it causes them harm. People with cancer often need strong medicine to help control their pain. Yet some people are so afraid of becoming addicted to pain medicine that they won't take it. Family members may also worry that their loved ones will get addicted to pain medicine. Therefore, they sometimes encourage loved ones to "hold off" between doses But even though they may mean well, it's best to take your medicine as prescribed.
People in pain get the most relief when they take their medicines on schedule. And don't be afraid to ask for larger doses if you need them. As mentioned in Opioids - for moderate to severe pain, developing a tolerance to pain medicine is common. But taking cancer pain medicine is not likely to cause addiction. If you're not a drug addict, you won't become one. Even if you have had an addiction problem before, you still deserve good pain management. Talk with your doctor or nurse about your concerns.
Tolerance to pain medicine sometimes happens.
Some people think that they have to save stronger medicines for later. They're afraid that their bodies will get used to the medicine and that it won't work anymore. But medicine doesn't stop working - it just doesn't work as well as it once did. As you keep taking a medicine over time, you may need a change in your pain control plan to get the same amount of pain relief.
This is called tolerance. Tolerance is a common issue in cancer pain treatment.
Newer developments
Intrathecal pumps
Only 2% to 5% cancer patients require interventions or the direct delivery of opioids to the central nervous system. Patients with unmanageable side effects may benefit from the epidural or intrathecal administration of opioids.
Approximately one tenth of the intravenous dose of an Opioid is needed when administered epidurally and one hundredth is needed when administered intrathecally. However, these procedures are expensive, and catheters and pumps are required to deliver the drug. To be cost effective, these devices should be used in a patient who has a life expectancy for longer than 3 months.
Radiofrequency ablation
This modality is becoming more popular in the present days. In this technique, the patient is sedated, an interventional radiologist uses a special needle to deliver radiofrequency current into the affected nerve, and destroys it. This procedure has fewer side effects and can provide pain relief for several weeks to months. It can also be repeated when necessary. It is used for ablation of intercostals nerves, trigeminal nerve, paravetebral nerves in the thorax and abdomen.
Vertebroplasty/Kyphoplasty
Used to treat painful vertebral body collapse/fracture caused by osteoporosis or tumor
Terminal stages: Palliative care
In the terminally ill cancer patients, conventional pharmacotherapy and even invasive analgesic therapy may not provide adequate relief of pain. In the very terminal phase, procedural options should be used relatively sparingly.
Options for the severe pain in this phase include subcutaneous infusions of opioids and/or sedatives.
Haloperidol and corticosteroids can be helpful symptom control adjuncts in the terminal phase. Comprehensive palliative programs for end-of-life care may be considered and can be inpatient or through home hospice. The physician should assess the needs of the patient and the family and fully discuss all care options. In addition to pain control, palliative care addresses the control of other symptoms associated with intractable cancer pain, including those relating to the physical, psychological, and religious or spiritual. Optimum quality of life is the primary goal of palliative care, which at the end of life is emotionally intense because of the multifactorial needs of the patient and family.
FAQ’s
Q. I'm afraid that if I use strong pain medicine now, there won't be anything left to treat my pain later, when it gets worse.
Pain medications don't work like this. Opioids used by themselves do NOT have a "ceiling" dose, meaning a level beyond which no more medication can be given. And if one opioid becomes less than satisfactory in providing pain relief, others may be used, as well as other medications and techniques for pain relief. There is ALWAYS more that can be done to ease your pain. Don't deprive yourself of your pain medication because you fear nothing can help later. It just isn't true.

Q. How should I take my pain medications? On regular scheduled basis or whenever required?
For cancer pain that is constant, or expected to recur; the best method of administration is to take the medication on an around-the-clock, scheduled way, such as a tablet every 6 hours. This means that you'll have a steady level of medication in your bloodstream.
If you are not experiencing constant or frequently-recurring pain, then it might be helpful to think about activities that appear to trigger your pain, such as walking or riding in a car, for example. If there is a link between the pain and something you do, then you can arrange to take the medication in sufficient time to have sufficient relief in place when you undertake the activity.

Q. I take my pain medications on an around-the-clock basis, but at times I have pain anyway. What can I do about this?
The pain you experience is called breakthrough pain, and you probably need a medication to handle that kind of pain, as well as the pain your around-the-clock medications are designed to ease. Breakthrough pain can occur for no obvious reason, or as the result of some activity that seems to trigger it, such as walking, coughing, etc. Regardless of the reason, it's likely that you'll need an additional medication to use during these times.
Q. Are these pain medications available freely?
Some pharmacies are reluctant to stock opioid medications, because of a variety of concerns. Speak with your health care provider or your hospital social worker or pharmacist to learn the names of pharmacies that stock the medication you need and arrange to have your prescriptions filled there.
Q. If I take strong pain medicines such as opioids early on, will I run out of options if my pain gets worse later?
Depending on need, opioids may be prescribed at any stage of treatment. There is no need to "tough it out" early in treatment out of concern that strong pain medicines won't be effective if needed later on. Some people, but not all, develop drug tolerance, which means their body has become accustomed to the medication. When a medication doesn't relieve pain as well as it did, the dose can be adjusted or another type of medication or treatment can be prescribed. Patients may receive increasing doses of opioids for years without becoming addicted, or psychologically dependent. When the need for pain relief subsides, physical dependence can usually be managed without withdrawal symptoms by tapering the opioid before discontinuing.
Q. What is palliative care -- is it the same thing as end-of-life care?
A major priority of Memorial Sloan-Kettering's Pain and Palliative Care Service is the incorporation of the principles of palliative care into the care of all patients with cancer from the time of diagnosis, not only in the setting of advanced or terminal disease.
Palliative care treatment:
• Affirms life and regards death as a normal process.
• Neither hastens nor postpones death.
• Provides relief from pain and other distressing symptoms.
• Integrates the psychological and spiritual aspects of patient care.
• Offers a support system to help patients live as actively as possible until death.
• Offers a support system to help the family cope during the patient's illness and in their bereavement.
Q. I take pain medications around the clock, and sometimes this means I have to wake myself up several times during the night to take a pill. Can this be handled differently?
Yes, very probably. It may be possible for your pain physician to switch you to a different form of your medication or to a different medication that is longer-lasting, one that will allow you to sleep through the night. Speak with your physician about ways to solve this. Your sleep is very important to all aspects of cancer management, including pain management.
References:
1. World Health Organization. Cancer Pain Relief. Albany, NY: WHO Publications Center; 1986.
2. Cancer Control. March/April 2000, Vol. 7, No.2
3. NCCN practice guidelines in oncology-v.1.2008
4. Cancer Pain Relief, Second Edition, with a guide to Opioid availability, World Health Organization, 1996.
5. Mercadante S, Fulfaro F. World Health Organization guidelines for cancer pain: a reappraisal. Ann Oncol 2005; 16(suppl 4):iv132-iv135.
6. Fine PG. The evolving and important role of anesthesiology in palliative care. Anesthesia Analgesia 2005; 100: 183-188.

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