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A Few Words on the Treatment of Chronic Pain

 

I treat addiction. Also, in the past, I have treated chronic pain. What I have found is that it is hard to find doctors who are aware of the clinical issues where these two disciplines intersect.
 

On one hand, the addiction professionals are not often involved with  pain management (although this is changing) and they are hesitant to  trust the patients. Most pain physicians want to do invasive medical procedures since that is where the money is. They vary with willingness to prescribe opiate medication.  They do not want to spend time talking about the pain medication.
 

Unfortunately, if a patient has trouble following the directions, the  pain doctor may not have the knowledge, time or inclination to identify  the roots of a problem. Problems  become the fault of a patient, who is identified as an ADDICT, rather  than the fault of an incomplete treatment approach. It is no wonder the patients become distrustful of the medical establishment and even distrustful of themselves. Many turn outside of standard medical care to obtain what they think they need. 


This situation has been complicated by recent regulatory changes in which doctors who treat pain are presumed to be doing something wrong.  Many doctors will no longer treat pain.


20 years ago, researchers such as Dr. Russell Portnoy of Beth Israel Medical Center  and others reported that opiate pain medications could be safely given  to many people in chronic pain without the emergence of addictive  behavior. 


However, in many cases, problems do arise. These drugs are habit forming and can cause long term physiologic changes and behavioral problems. You can’t just throw opiates at everyone in pain and ignore the consequences. Therefore,  even when pain is real, pain medication use has to be closely  monitored, adjusted when necessary or even discontinued when the overall  affect of the treatment is negative. Many patients, even those with true pain, will do better when their pain medications are discontinued.


Opioids will also increase pain in a process referred to as opioid induced hyperalgesia.  This is different from withdrawal.  Both processes increase pain and suffering


In my own practice, I have seen the majority people come off of medication with good outcomes. These are people whose injuries had occurred some time in the past and who are stable on medication regimens. They made a voluntary decision to stop the medication. During a careful weaning process, they did not experience long-term or severe exacerbations in pain. As the doses became lower, the person became more active in their work and family. It was as if the drug took an edge off their ambition and caused a state of decreased motivation.  
 

A minority of patients responded badly to weaning. They experienced increased levels of pain, decreased ability to participate in work and other activities. They did better remaining on the pain medication.   Current recommendations are to use buprenorphine or methadone for these patients
 

 I no longer to chronic  treatment with opioids unless the opiod used is Suboxone or Subutex.  The  regulatory environment means that a bad outcome with a patient  will lead to attempts to discredit the physician.  Since I have chosen  to embrace the treatment of patients with a history of misuse, I will  see bad outcomes more often.

In this website, I have attempted to present the medical science underlying both addiction and chronic pain.

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What are the different types of pain

  

Nociceptive Pain-(twisted ankle, burn)
 

This is the term for normal physiologic pain.  There are microscopic sensors in the skin that respond to very intense stimuli.  The are also free nerve endings throughout the body that respond to inflammation seen with acute injury.  Signals from these sensory organs go through a special pain signalling pathway in the spinal cord which is distinct from that which communicates non-pain stimuli such as touch, cold, vibration and other sensations.  It is the activity of this pathway that causes the pain.  Glutamate and Substance P are two of several neurotransmitters that modulate the forward transmission of pain stimuli through this pathway to the brain.
 

Visceral Pain- (i.e. kidney stone, appendicitis)
 

This refers to pain emanating from our gut as well as other internal organs. Unlike the skin or limbs, there is no additional input from fine touch sensors; therefore, we cannot easily localize the source of the pain. When the pain is acute or intermittent, there is often an inflammatory component.  When chronic, it is often due to nerve damage or just a sensitivity to intestinal muscle function (i.e. irritable bowel syndrome)
 

Opiates are helpful for this pain but can easily backfire.  The constipation caused by them can make the pain worse.  The nausea and/or cramping associated with their wearing off can often be mistaken for a recurrence of the underlying pain and leads to continual and/or increasing drug use.  This can cause patients more discomfort than the original problem.  
 

Neuropathic Pain- (shingles pain, pain related to nerve injury in back or neck, trigeminal neuralgia)
 

This is a type of pain that occurs secondary to nerve injury.  After injury the remnant pain nerves may fire more often.  Additionally, the specialized pain tracts in the spinal cord react too easily to the primary pain nerves coming from the body; they fire more often causing more pain.  This lowered threshold may be due to abnormal processing of glutamate and substance P.  The result is that stimuli that are supposed to be mildly uncomfortable are more uncomfortable.
 

There is also an attempt for an injured nerve to reestablish connections in the spinal cord. Many times, these connections are faulty and injured sensory nerves connect with the pain tracts by mistake.  The result is that normal sensation will be sensed as painful sensation.  
 

It seems that the above abnormalities can get locked in for a long time.

Compared to other pain types, neuropathic pain is relatively insensitive to opiates BUT opiates may give still give significant relief.  Medicine like neurontin and lyrica are able to reduce the signalling from glutamate and substance P.  This is why they are useful for some patients with this type of pain.
 

Sympathetically mediated pain -Causalgia or reflex sympathetic dystrophy
 

This is a subset of neuropathy where the injury and/or abnormal signal processing affects the sympathetic nerves.  These are the nerves that control blood flow, temperature, sweats and other functions in the body.  For this reason, the pain is associated with abnormalities in swelling, temperature changes, and color changes in arms/leg.  

This can be an intense pain and is very difficult to treat

Myofacial pain
 

This referrs to pain that seems limited to the muscles and or their connective tissue. There is often a component of muscle spasm.  It may be due to injury although sometimes it is more chronic.  
 

The inflammatory component is one reason that doctors do trigger points; it reduces inflamattion in a targeted area.  Also, when these areas are numbed by novocaine, the muscle spasm may resolve.  
 

Fibromyalgia  

This is a poorly understood disease.  There seems to be an abnormality of the central nervous system in which pain impulses are not being appropriately processed and the secondary nerves in the spinal cord fire too easily.  Since the problem seems to be in the secondary nerves, we have often prescribed neurontin and/or lyrica which help reduce this type of nerve transmission.

Headache
 

Another syndrome of pain that is hard to characterize.  There many be components of muscle spasm, myofascial pain, inflammation from leaky blood vessels and/or neuropathy.  Treatments are varied depending on what the doctor believes is going on.  Unfortunately, it often means the doctor's bias rather than the true nature of the pain (which can be hard to discern) runs the course of treatment.
 

SUMMARY
 

When there is chronic pain there will usually be some component of neuroadaptation: changes in the central nervous system that serve to facilitate pain. This may lead to pain hypersensitivity.  And remember, the use of opiates, which result in tolerance and withdrawal, may cause a rebound increase in pain signalling and increased pain when the drugs wear off.

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Non controlled medications to treat pain

Additional Information

There are a number of medications, other than opiates, that are useful for treating pain.  It is unfortunate that so many of my patients are maintained only on opiates without utilizing the full range of medications available to them.  Many of these medications are used in combination, each one chipping away at part of the pain and allowing the patient to use less habit-forming medication or, at least, stabilize on a certain dose.   

Tylenol- (acetaminophen)   

This medication helps in mild to moderate pain.  It is well tolerated and should not be forgotten about.   

Non-steroidal drugs- (Motrin, Naprosyn, Voltaren)   

These drugs have also been around a long time.  After an injury, the cells release chemicals that cause swelling and increase the firing of pain conducting nerve cells.  By decreasing these inflammatory proteins, we can reduce pain and swelling.   They can cause stomach upset and bleeding, water retention, kidney and liver problems.  Many are inexpensive and most people are quite familiar with their use.    

They have also been implicated in causing a very slight increase in heart problems.  This risk is only seen with chronic use and seems to range from 20% to 50% depending on the drug. We must keep this issue in perspective.  A 50% in the risk of a heart attack means that a person who had a risk of 4 in 1000 before they took a medicine may now have a risk of 6 in 1000.    Only your doctor can decide if this is a reasonable alternative   

Cox-2 inhibitors-Celebrex, (Vioxx, Bextra) These drugs are closely related to the non-steroidal drugs but focus their effect on specific types on inflammatory processes.  They are better for the stomach (but not absolutely safe) but may be more likely to cause other problems.  They tend to be more expensive.  You should use them to avoid stomach upset; otherwise, the older non-steroidal drugs are just fine.    

There has been a lot of publicity about the increase in the risk of heart problems.   The increase in risk ranges from 20% (Celebrex) to 50% (Vioxx).  The risk is a concern; however, I do not know if being in inactive from pain or subjected to side effects from other medications is any safer.  

Anti-depressants- amitriptyline, norpramin, desipramine, Effexor, Paxil, Cymbalta, Pristiq others

It has long been appreciated that many drugs used for treating depression also relieve chronic pain.  Part of this effect may be related to relief of depression.  Depression is common in the pain population and the depressed patient is less able to tolerate pain.  However, these medications also relieve pain in persons who are not clinically depressed.   The mechanism for this is not understood.  The brain is very redundant.  Many of the neurotransmitters used in the control of emotions are also active in pain transmission.  Some of the older or TRICYCLIC agents have been well studied.  These drugs tend to be active against norepinephrine.  The pain relief may take several weeks to manifest.  


“Muscle relaxers”   Robaxin, Flexeril, Skelaxin, baclofen, tizanidine, Parafon Forte, Soma, others   

Contrary to their name, these drugs do not relax muscles.  Physiologic tests reveal that muscle tone does not change.  What seems to be happening is that these drugs modify the pain of muscle spasm.  It is believed to occur due to a central nervous system mechanism; these drugs act on the brain and spinal cord.  

Despite being lumped together, many of the drugs work by different mechanisms.  This gives a rationale for trying several different agents. Many addiction professionals maintain a healthy respect for these medications.  Any centrally acting pain relievers may have a potential for abuse.  It would not surprise me that any of these drugs would be subject to abuse.  I have only seen consistent problems with Soma (see The Trouble With Soma).  However, I did have a problem once with a patient misusing baclofen.

Valium- I bring up Valium because it is a true muscle relaxer.  It is also a sedative.  In unusual cases, I have used it to relieve spasms.  Usually, I try to avoid these types of medications.

Anti-epileptics   Neurontin, Lyrica Depakote, Topamax, Lamictal, etc.    Over the years, one anti-epileptic drug after another has been found to be effective in relieving pain.  Neuropathic pain has been one type of pain in which these drugs have been very useful.  In fact, I would consider these drugs first line with anyone with neuropathic pain.  

The mechanism of action is not clear.  It is thought that these drugs indirectly reduce activity of the NMDA receptor, a receptor involved with pain transmission.  Neurontin and a newer medication, Lyrica, have had their mechanism of action worked out.  A specific receptor in one nerve is blocked thereby reducing the amount of glutamate released.  It is the glutamate that stimulates the NMDA receptor in the nervous system that facilitates the transmission of pain impulses.  

It is unclear if the other drugs have similar modes of action.  Knowing specifically how they work can provide a rationale for switching between them or using them in combination.

Lyrica is the newest agent (available since fall 2005)   I have found it more effective than some of the other agents, even in persons who did not respond well to other anti-epileptics.  

A major problem with these medications is their tolerability.  I find 25% of my patients cannot tolerate these medications.  Fatigue, dizziness and stomach upset are the most common problems.  Older medicines, like Tegretol, are also associated with liver and bone marrow problems.  The newer agents are safer.  

Neurontin has the most clinical experience and is often used first.  An additional problem with Neurontin and Lyrica has been weight gain.  However, Topamax has been associated with weight loss.   

Anti-arrhythmic- Lidocaine, mexilitine   Anyone who has gone to the dentist or received stitches is aware of effectiveness of topical anesthetics like Novocain and Xylocaine and others.  Lidocaine has a similar mechanism of action and has been available for decades.  Its’ use has been to stabilize heart rhythms after a heart attack.  Unfortunately, it is available for use only through the vein or embedded into a topical patch.  The patch is effective but only gives pain relief in the areas around where it is applied.  

Mexilitine is also used as a heart medicine and is available as a pill.   It turns out that these medications given systemically will reduce pain.  Many clinics have set up protocols for intravenous Lidocaine infusions of several hours.  This does relieve the pain but often the effect is short term.  Mexilitine, a pill, can give more long lasting effects but I have not found it that effective.  Side effects relate to the heart; they can cause problems with slowing of the heartbeat.    

Alpha-2 agonists- clonidine, tizanidine  Nerve tracts from the brain descend down the spinal cord and can affect the upward transmission of pain impulses from the spinal cord.  Clonidine is an effective blood pressure medicine.  Tizanidine has been used as a “muscle relaxer”.   Both medications can relax activity in certain areas of the brain.  This results in less pain transmission.   Unfortunately, I have not found them to be terribly effective although it does work on some patients.   

Capsacin Cream This is an over the counter cream that is effective in any area you might rub it into.  It works first by stimulating free nerve endings in the skin that can cause more pain.  However, after constant stimulation, these nerves turn off and there is less pain.  It may take several days for the increased pain to give way to decreased pain and weeks to see maximal improvement.  The cream is expensive and has to be put on several times a day for maximal effect.  For localized pain of all types this remains an excellent alternative. 

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Long acting opioids for pain- Methadone and buprenorphine

There are only two long-acting opiate medications: methadone and buprenorphine.  Buprenorphine is the active ingredient in Suboxone and Subutex,  These are medications that are metabolized slowly.  The time it akes to metabolized half the methadone in the body is almost a day.  The time to metabolize half the buprenorphine is 36 hours.
 

Methadone has long been associated with heroin use because it has been used to stabilize opiate-dependent patients. In fact, buprenorphine has also been approved for this indication and will, unfortunately, also become associated with drug abuse. This has led, or will lead, to the stigmatization of use of these medications.

However, they are great pain medications. Methadone was used as a pain medication for 20-30 years prior to its’ being adopted by the addiction medicine field. In fact, recent reports in the media have revealed that President Kennedy was using this medication for a chronically bad back (It was in the mid to late sixties that methadone came to be used for addiction). 


The main benefit of methadone is that there is no  dip in pain relief during the day.  It is quite inexpensive and easily represents the cheapest way of treating pain. Even though, the half-life of methadone is quite long, clinical experience has shown that the pain relief only lasts about 6-8 hours after taking the medication. There is no explanation for this.  Therefore it is usualy dosed 3-4 times daily.
 

Unfortunately, many persons with chronic pain have been referred to methadone maintenance treatment programs for pain management. These programs are designed for addiction treatment and are heavily regulated. They are forced to give the medication once daily to a majority of their patients. Many patients with pain will tell you that their pain returns in the afternoon and can worsen as the day and evening progress. 

Over the last couple of years, scientists have learned about another major benefit of methadone. It has to do with the isomeric variant. When a drug is created in a lab, both the drug and a mirror image (isomer) of the drug is made. It had been thought that that this isomer was inactive. In fact, the isomer can block activity at the NMDA glutamine receptor. This receptor is responsible for aiding in the transmission of pain. It may also be a major cause in the development of neuropathic pain. By blocking this receptor, there is a reduction of pain. In addition to pain relief, blocking the receptor has been linked to reducing the development of tolerance to the methadone. For this reason, pain relief with methadone may be longer lasting than with other opiates. 

Methadone will accumulate in the body.  This has several consequences.  If we try to titrate up the dosage too quickly, someone can overdose.  Also, the first dose may not lead to overdose whereas the a second or third dose might.  This is the basis of a lot of malpractice suits.
 

Another consequence is that it is more potent at higher doses.  !0 mgs of methadone is equivalent to 20mgs of oxycodone at a low dos.  At a higher dose, it is equivalent to 50 or 60 mgs.  This is one reason it may be harder to wean from than other opiates.
 

It may be more likely to cause nausea and fatigue. It will cause more sexual hormonal disturbances than most opiates.  Woman lose their periods and men have their testosterone levels lowered.  There is no truth to a common misconception that it gets into the bones; although, osteoporosis can be more likely secondary to the sex hormone imbalances.  

Methadone, like all opiate drugs, is a safe medication.  Recent experience, however, have caused doctor to be extra cautious.  There has been evidence that it affects the electrical rhythm of the heart which may result in a life threatening process.  There is also a greater chance of respiratory  depression even when used as directed.  Despite the severity of these problems, their incidence is quite low and the drug can be used safely in many.


Buprenorphine has been available for over 15 years. It was originally approved as an injection.  It now comes in a pill form (or a dissolvable film) that is place under the tongue. The medicine has to be absorbed from underneath the tongue. Any medication that is swallowed will be metabolized by the liver and lost. 


It is more potent than morphine. This makes doctors nervous because they really do not understand what potency means. High potency does not mean a drug is stronger. It means that a similar effect is achieved with a lower number of milligrams. 0.3 mgs is equivalent to 10 mgs of morphine. Therefore it is 30 times more potent as a pain reliever. However, with increasing dosages, the effect of morphine increases to a greater degree than buprenorphine. Also, buprenorphine causes minimal intoxication no matter what the dose. So, even though it is more potent, it is less powerful and less intoxicating. In fact, it is the best drug in terms of tolerability.


It is not as powerful as many other opiates; however, I estimate that at least 2/3rds of patients will get adequate relief. I estimate that the maximum effectiveness is equivalent to about 180-240 mgs of morphine. If someone is already on large amounts of pain medication, switching to buprenorphine can be associated with withdrawal.

Since it is not as intoxicating and has a plateau in its’ effectiveness, it is not as addictive as other opiates. It also acts as a blocker for other opiates. I tend to use this medication either in persons who have been unreliable in the medication use or in persons who could not tolerate other drugs. 



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