Tag Archives: Anticonvulsants

Phantom limb pain

Phantom Pain is a form of nerve pain appearing to arise from an area of the body that has been removed or amputated. This pain can affect mastectomy patients as well as patients with simple tooth extractions. Phantom sensations of some kind are almost universal in patients that have undergone limb amputations. Significant pain occurs in as much as 80% of these patients, but seems to improve over time in at least half of these patients.

The cause of phantom pain is not fully understood. It is important to emphasize that the pain is not imagined, and is not the result of a psychological or emotional disturbance.

Phantom pain is the prime example of neuropathic pain; i.e., pain that is caused by a damaged or malfunctioning nervous system. Therefore, all the medications that are used for neuropathic pain can be useful for phantom pain. This includes anti-convulsant and antidepressant medications. Transcutaneous electrical nerve stimulation (TENS) of the stump can occasionally provide relief. Interestingly, stimulation of the intact, opposite limb is often more effective. In some patients, rehabilitation with active exercise and use of the stump and a prosthesis can be the most beneficial treatment. Placement of spinal electrical stimulators has had mixed results, but if the pain has been refractory to all prior treatments then this should be considered.

It may be most appropriate to target the initial injury that precipitates the enduring neuropathic pain. In fact, this is already done by the use of pre-emptive anesthesia during surgery. The surgeon uses a local anesthetic to deaden the nerves as well as a general anesthetic to immobilize the patent for surgery. Another possibility may be to suppress the immune system for the initial five days after injury. This may curtail the inflammation associated with peripheral nerves that appears to trigger many aspects of neuropathic pain.

A recent article in Psychiatric Times by Steven A. King reported that while the “apparent neuropathic nature of phantom limb pain (PLP) would suggest that antidepressants, anticonvulsants and similar medications would be most efficacious. Most (PLP) patients are treated with acetaminophen, nonsteroidal antiinflammatories and opioids.” A survey article by M.A. Hanley and associates found that just over half of PLP patients, and over one-third of severe PLSP patients, “had never been treated” at all for their pain.

from The Richeimer Pain Institute

Medications

ANALGESICS.

i) Non-steroidal anti-inflammatory drugs (NSAIDs) have been used for 150 years in Europe, and probably for a great deal longer in the East, in the form of willow bark extract. Useful when given appropriately, examination of the chronic pain population indicates that a very high number of patients are intolerant to these drugs because of gastrointestinal or other side-effects. There are two possible hypotheses for this. Firstly, chronic pain sufferers tend to be somewhat hypochondriacal and intolerant of body symptoms in general and thus less tolerant of real or perceived side-effects when taking medication. The second is that there may be a sub-group of patients whose pain is not managed well early on. NSAIDs may produce side-effects, limiting their use. With no pain relief, the patient fails to exercise. This hampering of their rehabilitation because of inadequate analgesia may contribute significantly towards the chronicity.

Recently COX2 antagonists have come on the scene, but the first wave of these have been disappointing in the UK, in that the side-effect profile does not appear to be particularly better than the present drugs (Meloxicam, Etodolac). The newer drugs, Vioxx and Celebrex, are now available in the USA and will soon become available in Europe. Their arrival is awaited with eager anticipation, but the results may prove to be disappointing. The products may not be as side-effect free as they first seem.

ii) The use of opioid drugs for the management of chronic non-malignant pain is fraught with difficulties, some real and some perceived. Morphine itself has tended not to be prescribed for chronic pain, because of a fear or stigma concerning Morphine. Physicians may fear dependence, tolerance and side-effects. There is a wide difference of opinion, which is still to be resolved; however, some patients can have their pain adequately controlled with opioids, without an unacceptable level of addiction problems. The potential risk of addiction remains a very real problem for a minority. Also, a significant number of patients with chronic pain complain of bothersome side-effects from medication. Mobility and distress must be monitored and benefits must accrue in both these parameters, as well as in reduction of pain.

iii) In the UK and in the USA, traditionally most patients with chronic pain receive an opioid derivative such as Codeine, Dihydrocodeine or Dextropropoxyphene. In the past Pentazocine and Buprenorphine enjoyed a passing vogue but are now little used. Pentazocine proved to have unacceptable side-effects, and Buprenorphine, originally thought to be non-addictive, was shown to have addictive potential and since being classified as a controlled drug has enjoyed little popularity. Nefopam has limited efficacy and popularity, and Meptazinol is short-acting, and often associated with an unacceptable level of side-effects.

Recent work suggests that Codeine and Dihydrocodeine are merely pro drugs for Morphine, and exert their action through metabolism to this compound. Given that a significant number of the population do not have the metabolic pathway to facilitate this, it is not surprising that there is a significant failure rate to produce any analgesia at all and that patients getting analgesia seem to get limited relief-hence possibly the popularity of these preparations being compounded with Paracetamol. There is good evidence that in some patients, much of the analgesic effect in these combined preparations lies with the Paracetamol itself, whilst many of the side-effects lie with the opioid.

v) Tramadol hydrochloride is an orally active, clinically effective, centrally-acting analgesic. It can produce analgesia that has been compared to Codeine or Dextropropoxyphene. It has been used in post-surgical pain, obstetric pain, cancer pain and chronic pain of mechanical and neurogenic origin. Analgesic tolerance is not a significant problem, and psychological dependence and euphoric effects are minimal. There are a significant number of patients in the chronic group who develop side-effects, but many of those who tolerate the drug get useful benefit in pain reduction. This slow-release formulation is an appropriate vehicle for chronic pain management.

Tramadol has an affinity, albeit relatively weak, for mu opioid receptors. It is also a neuronal uptake inhibitor. The monoamine neurotransmitters 5HT (Serotonin) and Noradrenaline (NA) are involved in the inhibition of spinal cord dorsal horn neurone responses to painful stimulation (i.e. closing the gate). Analgesia can result from activating the pain inhibitory pathways originating from higher CNS levels, and containing these neurotransmitters. Tramadol inhibits the uptake of 5HT and Noradrenaline but not Adenosine, Cyclic AMP, Dopamine, or Gaba.

Metanalysis by Moore and McQuay indicates an appropriate dose response curve for Tramadol, and suggests a reduced number needed to treat to show therapeutic efficacy as compared with Codeine, in doses of 75 to 150 mg. Nausea, vomiting and dizziness are greater than with Codeine, somnolence about the same and constipation much less. In the chronic pain situation nausea and vomiting are attenuated with usage, as is somnolence for both drugs, but constipation remains a particular problem with Codeine and Dihydrocodeine, and less of a problem with Tramadol.

Side-effects from Tramadol can be minimised by starting with a low dose and increasing gradually. There is evidence that this reduces the side-effects and improves tolerance. According to need, it can be started in a low dose of 50 mg daily or twice a day, and gradually titrated to reach 50 mg three times a day by day 3. Once a patient is established on a therapeutic dose, they can be put on the slow-release formulation to provide round-the-clock analgesia.

B. PSYCHOACTIVE DRUGS.

i) Anticonvulsants are well acknowledged as being effective in the management of shooting pain, for example: trigeminal neuralgia and the shooting element of neurogenic pain, such as post-herpetic neuralgia, diabetic neuropathy and similar conditions. Carbamazepine appears to be the most effective drug although there is a higher incidence of side-effects than with Sodium Valproate. Recently Gabapentin and Lamotrigine are enjoying popularity, either as “add on” drugs, or as sole agents. Further drug development of these types of agents might produce useful efficacy in the future.

ii) Tricyclic antidepressants are one of the most commonly used analgesics in pain clinics. This is not for the specific antidepressant action, but is more associated with the activation of pain inhibitory pathways. This appears to be less of a feature with the tetracyclic agents, and has meant that their usage in chronic pain has as yet remained unproven. This is of course is disappointing as the side-effect profile is significantly better. The sedative effect of Amitriptyline can be harnessed to good usage by giving the tablet one or two hours before retiring, and it should not be used during the day.

ANALGESIC PAIN MANAGEMENT

In general, patients with pain can be given a trial of Paracetamol. An appropriate non-steroidal can be used if there is an inflammatory process, and continued if these are effective and if side-effects are minimal. The next optimal step in the analgesic ladder will be the use of agents like Tramadol, Dextropropoxyphene, or Dihydrocodeine, with long-acting preparations being ideal for chronic pain. At present, slow-release Tramadol would appear to be the most effective drug in chronic pain for this group of patients. If side-effects preclude its usage, one of the other agents can be considered.

Finally a small group of patients might be suitable for the use of opioids themselves.

In conjunction with this ladder, anticonvulsants and tricyclic antidepressants can be considered, for their specific and appropriate actions on shooting and burning pain, usually of neurogenic origin.

You are the expert of you

“You are the expert of you,” says Krista Brecht, a nursing and chronic-pain specialist at the pain centre. “You come with a suitcase filled with things that can be helpful, like the professor who devised a way of working on a computer while lying down because sitting was too painful. We help you to identify those things and help you to become more self-reliant.”

Today Berardinucci undergoes physiotherapy regularly, meditates or relaxes in a hot bath about five times a week and makes a point of walking daily. Some relief came when surgery reduced pressure on her spinal cord. She’s also been given morphine and a drug cocktail that features a new anticonvulsant, a recent addition to the pain centre’s treatment arsenal. As her pain has become more tolerable, her interest in life has been renewed.

An early proponent of biofeedback and of morphine for noncancer pain, the pain centre is constantly in search of new tools. Anticonvulsants used to combat epilepsy and small doses of tricyclic antidepressants, for instance, have proven useful for many patients.

“Scientific research into pain,” says the centre’s Gary Bennett, “is one of the most productive areas of neurological research right now.”

The pain centre is currently setting up a one-year pilot study about the potential benefits of smoking marijuana for chronic neuropathic pain. “We do not recommend cannabis to patients, but we have had good reports from patients using it for neuropathic pain,” says Dr. Mark Ware. “We would be interested in the possibilities of cannabinoids in the management of pain once clinical trials are completed.”

According to the most recent Health Canada numbers, 786 Canadians are legally permitted to possess marijuana, of which the majority (about 600) can also grow it for their own use. Former pain centre neurosurgeon Dr. Joseph Stratford says, “I know of patients whose lives have been changed for the better by smoking marijuana.”

Encountering patients at the centre with intractable phantom-limb pain after amputation impelled one young doctor, Joel Katz, to see if administering a local anesthetic as well as a general one during surgery could prevent pain. Previously, Melzack, Katz and Terence Coderre had studied the effect on animals and discovered that local anesthetic protects the body from postsurgical pain. A general anesthetic alone does not.

Convinced by their results in both animals and people, a growing number of anesthesiologists now use local anesthetics as a preemptive strike against postsurgery pain.

When Dr. Mary Ellen Jeans saw how some of the centre’s patients were aided by acupuncture—which stimulates major nerves—she began to test a noninvasive treatment involving electricity, called transcutaneous electrical nerve stimulation (TENS). Today hundreds of people undergoing physiotherapy benefit from TENS. Patients affix electrodes to painful areas or at nerve points, then switch on a mild battery-powered electrical current from a device that can slip easily into a pocket. Milena Svraka, 52, was referred to the clinic after being mugged one night by two men, one of whom punched her in the face and dragged her across the pavement by her right arm while the other kicked her in the legs and body. She didn’t go to emergency because nothing felt broken but visited her local clinic the next day. The doctor said her muscles were strained and prescribed a few days of rest.

Back at work, Svraka couldn’t ignore the pain in her back, neck, right shoulder and arm. Determined to find out what was wrong, she saw a variety of medical practitioners, and still got no relief. When she couldn’t stand the pain any longer, she revisited the clinic, where her doctor recommended she take an indeterminate sick leave.

Svraka, who had travelled widely and rarely taken a sick day, now felt confined to the house. “Pain changes who you are. I wasn’t up to being jostled by people on the bus or metro. I was in so much pain, I just wanted to curl up and have it stop.” On a neurosurgeon’s referral, she was directed to the pain centre.

After a consultation, Svraka was put on a low-dose antidepressant, tried traction therapy—used to relieve joint compression, promote soft-tissue stretching and improve circulation—and began treatment with TENS. “I started feeling warmth returning to my arm right away,” she says. She used the arm more and began to regain the ability to turn her head from side to side—something she hadn’t been able to do in years.

She has since added everyday chores to her list of what is possible—such as stirring pots and peeling vegetables—and continues to use her TENS machine daily, affixing electrodes to her arm, neck and shoulder areas. The gentle pulse emitted releases endorphins, relaxes the surrounding muscles and seems to close the gateway to her pain.

Today her pain is a bearable three or four on a good day. “I can do things I love again, like gardening and going for walks.”

Linda Chown had successfully blacked out the memory of a bicycle accident she had at age nine, when she flew over the handlebars facefirst into a telephone pole. Her two front teeth remained embedded in the pole, and she endured four years of treatment to restore them. When, as an adult, she began suffering unrelenting face pain and severe migraines, a friend suggested she try osteopathy. While being given a facial treatment, she suddenly recalled the accident, and the shock and pain came flooding back. Later, when the nearly unbearable pain wouldn’t go away, she was referred to the pain centre.

A psychologist, Ann Gamsa, was called in and worked with Chown on many personal concerns, including her failure to remember much for a period of time after her accident. Seeing that her difficulty in expressing certain feelings was likely a factor in her pain, Gamsa helped her patient look at the accident and its aftermath, discussing the shame, anger, fear and pain it caused. The intensive work, along with medication and coping strategies, sharply reduced Chown’s suffering. It also left her grateful that not only her body but her mind was treated, too.

Today other pain centres across Canada follow the MUHC Pain Centre’s proven formula of combining physicians with varying specialists. But much remains to be done in educating the world about pain.

“There are still many practitioners who blame the patient,” says Gamsa.

“That is useless, unfair and wrong.” Despite a stack of research supporting the use of opioids such as morphine to relieve long-term pain and research that proves pain sufferers rarely become addicted, many doctors are still unaware or unconvinced.

“Montreal is light-years ahead of us in Ontario,” says anesthesiologist Dr. Ellen Thompson. “Under the rules of our College of Physicians and Surgeons, any doctor can refuse to treat a patient with opioids.”

Still, in the medical world, little is known about most forms of chronic pain. Researchers have only recently begun to study the differences between chronic pain and the passing pain that accompanies a broken arm, a heart attack or surgery. Work has also shown that unchecked pain changes the body at the cellular level, creating conditions that can continue to cause pain even after tissues have healed or disease is conquered.

As yet there is no magic bullet for the treatment of chronic pain. Researchers have been looking for safer and more effective alternatives to morphine and other related opioid analgesics for more than a century. In the past decade, they have developed a new series of drugs called delta opioid receptor agonists. “These drugs mimic the effects of chemicals already found in the body, and studies suggest they may be effective painkillers without producing morphinelike side effects,” says Steve Negus of the Harvard Medical School.

Researchers are also assessing the usefulness of new creams, exploring whether genes predict pain sensitivity and looking into theories that, down the line, could stop pain before it starts.

Says Milena Svraka: “I went to the MUHC Pain Centre to find a better treatment and what I could do to help myself. I found out that a good day can be a miracle. Simply having less pain can be a miracle.”