December 2016 was quite a month for articles about pain control and several discussed innovative methods for delivery of critical drugs.
Neuropathic pain is pain that originates with an injury to a nerve. There are lots of options for treatment out there that have many side effects and don’t work all that well. Taking the concept that release of Calcitonin gene related peptide (CGRP) is involved in a lot of the pain, researchers came up with a novel delivery system to deliver a CGRP antagonist. The system of delivery involves something called a microneedle patch. The patch contains dissolvable microneedles that contain this antagonist. It is placed over the area that the nerve(s) are damaged. It has shown to be very effective in rats. Yes, at this time it is only at the rat stage, but this a promising therapy and delivery system. Hopefully it will move quickly through the approval process.This was from the ACS Nano 2016 Dec 21 journal.
The Journal of Alternative and Complimentary Medicine 2016 Dec 18 had a research study on Goshajinkigan (GJG). This comes from Kampo, a traditional Japanese complimentary medical treatment. GJG is a mixture of materials from 10 different plants. In this study GJG was used at a dose of 7.5 mg for low back pain. In patients without spine disease, GJG provided significant relief of low back pain. GJG is used for many different disease states. It must be kept in mind that there are 10 ingredients to this GJG and this makes it a fairly complicated treatment. If you insist on using complimentary medicines as a treatment regimen keep this in mind.
There is a nice review article in the Journal of Photochemistry and Photobiology Nov 2016 on using LLLT (low level laser therapy) for neuropathic pain. The use of lasers in the treatment of pain has not been around for very long. The first publication was in 2003. Lasers are now found in many settings which are fairly cheap and easily accessible. This article attempts to define the therapeutic window that is best for laser therapy treating pain. The secondary focus is that it is non-invasive and has few contraindications.
The ability for LLLT to work has to do with the reduction of fibrinogen levels, reduction of edema, and reduced inflammatory cells. There is also an increase in endorphins (bodies own opioids).
The lasers are usually 635nm and a low energy density of 5-500 mWs. The biological effect of a laser irradiation on a cell is called photobiomodulation. Light is radiation energy. It is measured in photons. THese photons have an effect on cellular components. Cellular behavior and function are affected (like COX 2 inhibition–also accomplished by Tylenol and Advil for example).Some of this enables the cell to repair itself.
The review found that LLLT is very effective in controlling neuropathic pain. The problem with the studies was the WIDE variation of density and power of the lasers.
Final conclusion was that more studies need to be done and come up with specific treatment protocols.
634 nM is the wave length/color, in this case red——infrared would be a wave length less than this
5mW–this is the power at the opening of the laser—5 milliwatts
neuropathic pain—complex pain that usually has nerve injury
Medical marijuana is not always Medical marijuana
The safe use of marijuana for medical purposes is one of the areas that mainstream medicine has let its patients down. Primary care providers should take more of an active role advocating for their patients in regards to marijuana. Used safely, marijuana and its separate components can help waylay a significant number of symptoms and decrease the need for narcotic prescriptions.
After using marijuana products for over 40 years to curb my resistant chronic pain, I spent 1000 hours reading and studying research papers on marijuana. Of the approximately 13,000 papers available, I reviewed 1500. This research helped me define medical marijuana. Based on this investigation, I wrote a handbook (Marijuana: It’s an Herb with an Asterisk) on how to use marijuana, the complete leaf and separate cannabinoids, safely. As part of my research, I checked with multiple dispensaries and concluded that what is being presented as medical marijuana to the consumer is not really medical marijuana as defined by the research.
Medical marijuana should be defined by its research and the parameters of that research. Almost all of the papers on marijuana, used as a treatment for medical purposes, contained the cannabinoid THC with a percentage less than 10%. THC is noted for its mind altering effects, but has many other effects beneficial to maintaining health. One of the other cannabinoids in marijuana, CBD, also has a concurrent percentage that is recommended if THC is used for medical use. An exact percentage of the best THC to CBD ratio has not been clarified. Again, THC and CBD are cannabinoids (chemical compounds) contained in marijuana. These two cannabinoids are the most active chemicals in treating medical conditions. Concurrent use of CBD with THC shows CBD providing protection against the negative effects of THC. Note: CBD should be used with THC if it is in a medical context.
When I started writing my book, the major discrepancies between science backed medical marijuana and currently dispensed medical marijuana became more and more obvious. Let’s start with the difference between medical marijuana (research based) and currently dispensed marijuana in relation to the THC percentage. Close to 100% of the research articles that focused on treatments using medical marijuana used less than 10% THC. Looking at multiple dispensaries from states that only allow medical marijuana, the majority of offerings were a THC over 20%. The research is also clear on another topic. If you are using marijuana medically, it is recommended that it contains some percentage of CBD (cannabidiol). The CBD is present to protect against the negative effects of THC and also has many of its own medical benefits. Many dispensary medical marijuana offerings have no CBD. Incorrect percentages and ratio of THC and CBD can significantly diminish their positive health benefits and unleash many negative effects. Problem: The majority of the marijuana carried by dispensaries have too high a THC content (over 20%) to be medical and a significant amount of their marijuana does not contain the recommended CBD.
Why does it make any difference if the THC percentage is too high? There is a question if it is medically beneficial (defined by science and research) and it maybe actively hurting people. THC percentages in the 1960’s and 1970’s were in the 2-4% range. The THC percentages of 10 medical dispensaries in 10 different states had 95% of their products in the range of 18-25%. Medical research with marijuana is done with less than 10% THC and mostly with at least 2% CBD. The increase in the number of motor vehicle fatalities related to marijuana has increased by almost 4 times as THC levels available increased. Fatalities from marijuana were stable at 3% of the total motor vehicle drug related fatalities for decades. It is now at almost 11%. The number of ER visits related to the side effects of marijuana (most are because of a psychosis) has sky rocketed. Most are related to the high THC content with no CBD. There is direct evidence that THC over 20% causes significant changes to the brain in the area of the corpus callosum, the area that lets the two sides of the brain communicate. Memory impairment and coordination are diminished related to the percentage of THC. Problem: Increase in motor vehicle fatalities related to high THC % causing decreased motor skills and increased ER visits related to high THC psychosis.
There is a near total lack of connection between medical research on marijuana and many of the current offerings of so called medical marijuana. You obtain a card to enable buying marijuana at a legal dispensary. The card needs to have a physician write a recommendation for marijuana use. The physician does not need to have any knowledge or training in the use of marijuana for therapeutics. With this card you can buy what is represented as medical marijuana from someone also not required to have any training. Along with this probably not being medical marijuana come the increased risks for many unwarranted side effects. Problem: Medical providers just write a recommendation for medical marijuana use with little training. The dispensary personnel are not required to have any working knowledge about medical marijuana.
The high level of THC, I believe, is consumer and profit driven. When we are talking about medical marijuana this is not acceptable. Medical patients using marijuana for health reasons should not be exposed to unnecessary risks related to too high THC levels and a lack of CBD. Medical marijuana is not about getting high. Most medical patients are unaware of the increased risks. Also, a number of consumers are masquerading as medical patients and are actually recreational users. This has been a factor in the push for higher THC percentages. Problem: Consumer driven high THC %, little patient knowledge base and lots of cards obtained by non-medical users.
Marijuana has significant health benefits and should be available for people with chronic medical conditions to help manage their conditions. As a physician, I feel our medical societies have failed us in not being more active in insuring that physicians have a knowledge base before recommending the use of marijuana. The patients also need to be knowledgeable about marijuana to protect themselves. Contrary to the usual opinion, there has been a large volume of research done on marijuana. Research has, in certain cases, had its hands tied behind due to the legal climate surrounding marijuana, but worldwide research gives us a path for safe use. There are many questions that still need to be answered, but we can proceed with a safe standard. Why have we decided not to take this path and not place some regulations and recommendations for medical use? Problem: No regulations according to current research.
The FDA has done little to pursue the current knowledge base about marijuana and recently decided to leave it in the class of the most dangerous illegal drugs with room for some increase in research possibilities. Close to 25 states have laws permitting medical marijuana of which there is little direction for its use. Shame on the FDA for being so political and nonscientific.
Be knowledgeable! The safe use of marijuana is possible, but it can also easily harm you.
In the latest issue of JAMA (Journal of the American Medical Association) Aug 9, 2016 there is an article proposing what a physician should do if a patient wants medical marijuana. As usual the American medical establishment is way behind on assessing a situation and coming up with some thoughts since medical marijuana has been around for a long time. But, better late than never, which is a poor statement for any kind of medicine. In the article there is reference to the different stages—1) first time it is brought up by the patient—-this visit should be well documented. If marijuana is being considered for this patient, a full evaluation should take place if one has not been done recently. During this eval the risks and benefits of marijuana for THIS patient should be discussed. 2) Other treatments that have been tried should be documented for success or failure. 3) The fact that the quality and concentration of marijuana is extremely variable should also be discussed. Cannabis Use Disorder and the potential for a psychotic disorder need to be mentioned in the side effects discussion. 4) It should be documented that it was discussed that the marijuana should be safeguarded against others using it. 5) There could be room for wider based discussions depending on the practitioners expertise in the area of marijuana.
The above is what your physician who writes you a letter of recommendation for marijuana should discuss with you. This is only the initial stage of preparation to use marijuana–if you are new to it. At this point in time all physicians should be knowledgeable on this subject but they are not–so you need to advocate for yourself and be informed.
Several situations have arisen recently that have changed the focus of chronic pain control. The main consideration is that the FDA has come out against using opioids for chronic pain–thus making prescribing physicians more vulnerable to being a causal agent (overdose, death etc.). This FDA ruling stems from the huge number of patients that are overdosing and dying from opioids–usually in combination with some other depressant. This has been going on for years –someone finally decided to do something about it. Unfortunately, they didn’t give many options for severe pain or patients already on opioids for years. Abuse of legal and illegal drugs is rampant in the US. In a normal lifespan, about 50% of people will have abused drugs. It was no surprise that over-prescribing of opioids by physicians, uneducated in pain control, would lead to massive abuses by patients. So–here we are–pain control without opioids–can it be done? Of course it can. Opioids were just the easy way out–at least in the beginning. Let’s look at it from this point of view–the view that almost every patient has a high potential for being an addict. A pain plan would need to keep this in mind and avoid highly addictive/high abuse potential medications.
The concept of multimodal therapy is inherent to not using opioids. This means that several different medications and treatment therapies will be used to replace the opioids. The usual ones are optimization of NSAIDS, acetaminophen, anti-convulsants and anti-depressants. Exercise regimens that include Yoga or Tai Chi are also considered standard (stretching and relaxing muscles and joints). Marijuana, with low levels of THC and high levels of CBD, has shown promise when in a multimodal treatment regimen. Newer to complimentary medicine in the US are Moringa and Andrographis Paniculata. Both of these herbs show promise in the area of musculoskeletal and arthritic pain. I believe physicians will need to become more familiar with complimentary medications along with exercise options if they are going to continue treating chronic pain patients and not use opioids. Also, psychiatric co-morbidities cannot be overlooked and need to be aggressively treated in the setting of chronic pain.
There are many books written about pain control without opioids (I wrote one called 21 Broken Bones)–as a patient,read a book and get to know your options. Always be aware of possible drug interactions. The more meds you are on the more potential for negative interactions. Ask your physician or pharmacist about you meds, if you have a question. You can control your pain without opioids–in the long run it will be a better alternative
Some chronic pain can’t be managed without opioids. This is less than 5% of all patients and even these patients can take LESS opioids with a good multimodal plan.
February and March of this year(2016) give us 2 good articles to review. The first is from the Journal of Comparative Neurology entitled ” Positive emotions and brain reward circuits in chronic pain” We have been aware for quite sometime that negative emotions can make your pain worse. It makes sense then that positive emotions could make it better. Why? Though the understanding of brain circuits and the apparent crossover of emotions and pain are not perfectly clear some answers have been forthcoming. The negative aspects of pain have a location that overlaps with areas that process reward and motivation. Pain relief is rewarding and can activate positive circuits. Lack of treatment or under treating chronic pain can maintain the activity of negative circuits making their feedback strong. Reinforcing the positive feedback can be done with good pain relief or possibly other methods of stimulation of this brain area.
Take advantage of this positive treatment loop and mentally reinforce it to increase the size and strength of the feedback. Get on top of your pain!
The second article is from the Br Journal of Pharmacology “Identification of A3 adenosine receptor agonists as novel non-narcotic analgesics” We are well aware that the treatment modes currently available are not adequate. This is the discussion of a novel therapy. Adenosine is a purine nucleoside and is everywhere in nature best known for its combination in energy transfer, ATP. It is also used in treatment of irregular heartbeats. It has 4 receptors of which the one important to us is the A3 receptor. This pain relief by stimulating the A3 receptor alone does not have cardiac effects. This target also uses our own intrinsic systems to give us pain relief.This gives us the thought that the effect on our bodies will be gentle and easily cleared from our system. Though in it’s infancy, early studies are very promising. Hopefully the research will continue to be funded.
Complex Regional Pain Syndrome (CRPS) has had many names prior to it’s current name. It has been called causalgia, Sudeck’s atrophy or reflex sympathetic dystrophy. The current name reflects the region nature of the disease and the many complex signs and symptoms that make up the disease. There are 2 methods used for diagnosis–the IASP and the Budapest criteria. It has been shown that the Budapest criteria is best for both clinical and research work. Inside of this is a group having chronic refractory CRPS–this is the most severe form of CRPS. It appears to effect women exclusively. The challenges related to CRPS have mostly to do with the fact that the numerous name changes and previously unvalidated criteria made research difficult. Now using the Budapest criteria this will change.
Pharmacologic management can be from IV, oral or topical sources. IV treatment would be with ketamine (a dissociative anesthetic or biphosphonates (usually used to prevent bone loss). Subcutaneous or IM doses of calcitonin have also shown some success. Calcitonin is usually used in calcium regulation or for osteoporosis. The specific goal would be for treatments that are all oral for ease of patient use.
Budapest criteria for CRPS: 1) Continuing pain that is disproportionate to any inciting event
2) Must report at least one symptom in 3 of the 4 following categories
-sensory: reports of hyperesthesia and/or allodynia
-Vasomotor: reports of temperature asymmetry and/or skin color changes or color asymmetry
-Sudomotor/edema: reports of edema and/or sweating changes
-Motor/trophic: reports of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or tropic changes (hair, skin, nails)
3) Must display at least one sign at time of evaluation in two or more of the following categories
-Sensory evidence of hyperalgesia (to pin prick) and/or allodynia (to light touch and/or deep somatic pressure)
-Vasomotor: evidence of temperature asymmetry and/or skin color changes and/or sweating asymmetry
-Sudomotor/edema: evidence of edemas and/or sweating changes and/or sweating asymmetry
-Motor/trophic: evidence of decreased range of motion and/or motor dysfunction (weakness, tremor, dystonia) and/or trophic changes (hair, nail, skin)
4) There is no other diagnosis that better explains the signs and symptoms
The biopsychosocial model for care may be the best. Yes, it is as it seems–you need to come from all the different sides of the problem. The possible biological origin which may or may not still be present, the psychological effects need to be addressed as well as the social changes that occur with chronic pain.
The whole patient needs to be assessed and treated. Begin treating the pain (pharmacologically) at the same time-modify maladaptive behaviors, improve coping skills, physical reconditioning to allow functional restoration, and stress management with relaxation techniques.
Careful titration of the pharmacological agents to minimize side effects, but under dosing can be a negative due to lack of full treatment potential.
Many therapies such as back fusions seem to have outpaced the research as to whether they actually are better–head to head studies do not show a great advantage from many types of fusions
A well rounded pain program involving all the biopsychosocial areas appears to be the best approach to controlling chronic pain. ASK to be included in this type of program
My book 21 Broken Bones has finally been published. It is a handbook on how you take the lead in your own care if you have chronic pain. It is short and to the point.
Almost all pharmacological agents are insufficient as single therapies in chronic pain. The goal is to start somewhere and look for a 30 % improvement in the pain score. When this is arrived at then each added agent should be held to the same standard–a specific reduction in pain. If it cannot deliver, then another agent should be trialed.
Antidepressants have been used for years in aiding pain relief. Their mechanisms for relief are complicated and varied. The most important aspect of these medications is that the ones with non-selective mechanisms work the best. For example SSRI’s (selective serotonin re-uptake inhibitors) do NOT work well to give pain relief. In general the mechanism of action of these non-specific anti-depressants in pain relief has to do with re-uptake inhibition of various neurotransmitters. Especially in the descending bulbospinal inhibitory pathways. One of the TCA’s (tricyclic anti-depressants) can be used preemptively in patients know to have a diagnosis of herpes zoster, which can be extremely painful. Cannabinoids (from cannabis) have also been used to inhibit descending pathways of the spinal cord to moderate pain. The antidepressant Duloxetine has been used successfully in fibromyalgia and neuropathic pain. It is particularly effective in nighttime pain relief.
Anti-convulsants are also used in pain. Their effector areas are more “at the site” of the pain as opposed to somewhere in the spinal cord. Examples of these medications include carbamazepine, valproate, gabapentin and pregabalin. Another anti-convulsant, topiramate, can be used in migraines. Many of the mentioned medications can also be used topically.
We must not forget some of the most commonly used non-prescription medications– Tylenol (acetaminophen) and NSAIDs such as Advil. The use of NSAIDs deserves a quick discussion of how it works, which could help keep you out of trouble while using it. NSAIDs work on COX 1 and COX 2 enzymes. Tylenol may work at a COX 3 site. They inhibit them. Most over the counter NSAIDs inhibit both COX 1 and COX 2. COX stands for cyclo-oxygenase. These enzymes are involved in the synthesis of prostaglandins. Prostaglandins are involved with inflammation but are also involved in protecting the lining of the stomach. Continued use of these NSAIDs could cause the breakdown of the stomach lining called an ulcer (with potential internal bleeding). Alternating Tylenol with NSAIDs is an option,if you are going to use them frequently. There are specific COX 2 inhibitors but they are not without their problems also. They can activate platelets and cause heart attacks if they are not taken with an aspirin. COX 3’s are probably somewhere in the cerebral cortex.
As you can see, having many options available helps keep the side effects down and still give you the pain relief you deserve.
We have COX inhibitors–Tylenol, NSAIDs—–antidepressants, anti-convulsants, cannabinoids from cannabis, and of course opioids—all can be delivered in various formats.