Summer 1995 Volume 4, Number 3
DR. BERDE: An important distinction to make is between acute pain and
chronic pain. One can experience acute pain because of a definable injury -
something as mild as a sprain, a fracture, or as horrible as total body
burns.
The process of injury sets up a series of chemical events that cause transmission of information via "action potentials" that go from the site of injury to synapse first in the spinal cord, and (then) to the brain.
There is no one-to-one correspondence between the amount of injury and the intensity of experience of pain. The state of the individual, previous experiences, expectation, motivation, a whole variety of factors, and, in particular, descending information - action potentials coming from the brain and brain stem downward to the spinal cord - can modulate, or alter, the experience of pain. So, acute pain is not a simple reflection of how much injury, but involves a variety of processes that are modifiable and change the intensity of that experience.
The good news is that there are methods to treat acute pain effectively. One of the simplest and oldest types of pain medication, aspirin, and newer medications that act like it - anti-inflammatory agents, such as Ibuprofen, Motrin, Advil - act on the processes that generate action potentials at the peripheral site in response to injury or inflammation.
Local anesthetics, in great measure, interrupt the transmission of action potentials from the periphery to the spinal cord.
Opioid medications, like morphine, act on the more complex processes of regulating and gating transmission in the spinal cord, brain stem and brain.
The most common old time way that people got pain medicine following surgery was by shots of, typically, morphine, or meperidine, Demerol - and you'd have to wait till you had a lot of pain in order to get another shot.
Morphine is effective, safe, and useful for most patients with acute pain, but the timing of being sleepy, being okay, being back in pain, being sleepy, being back in pain, gives the worst of both worlds. It creates more anxiety; it creates problems with side effects; it makes the patient feel helpless; it creates a harmful interaction with one's caregiver.
Other methods are commonly used to give morphine in a more effective way. One is by patients administering it themselves. The so-called patient-controlled analgesia pump allows the patient to get out of pain quickly without having to beg, to determine the dose to individual variation in requirements, and to have a sense of control, in a situation that would otherwise be characterized by vulnerability and helplessness.
There is great concern also in how treating acute pain improves the course of recovery - particularly following chest surgery where, if you make somebody comfortable enough to take a deep breath, they might be too sleepy to take a deep breath.
A number of methods have been evolved to optimize delivery of pain medications in that setting. In one of them, a local anaesthetic and an opioid medication are infused into the epidural space that involves both interrupting ascending information and facilitating descending inhibitory transmission and modulating the transmission of pain towards the brain.
Acute pain ought to be treatable in most cases; we have methods to do it. The problem is in not applying existing knowledge in most settings. But chronic pain is very different.
DR. BORSOOK: Chronic pain is the issue; we don't know very much about
it at a basic science level.
I have examples of two patients, one of whom is mine. One is a young woman of 32 who has a tumor in her brain that involves the very pathway involved in pain transmission - a part of the brain called the "thalamus." Damage to the thalamus in this lady produced a severe pain on the opposite half of her body, from head to toe. She cannot be touched; wind will cause incredible pain. This kind of pain we don't understand, but we do know that it's damage to the very pathways involved in normal pain transmission.
You can also get a chronic pain due to damage of peripheral nerve. The second patient has evidence of post-herpetic neuralgia. Post-herpetic neuralgia is a disease that comes on mostly in patients who are debilitated by disease, such as cancer. A virus present in all of us then comes out and produces vesicles. In this patient, we see lesions in the regions of specific nerve distribution; the virus has produced ulcerations and caused damage in the fifth cranial nerve that normally provides sensory information.
Many neuropathic pain patients have the same kind of pain that I talked about in the previous patient: pain in an area which is now "anesthetic" - the patients do not feel light touch or a pinprick, yet, if you give them certain sensations, they have increased pain and are in continuous pain.
DR. BERDE: The normal experience of pain is a very protective one. If one does not have sensation of pain, it doesn't protect you from burning your fingers on a stove or a variety of other things. But there's nothing particularly protective about the pain of the young lady with cancer; pathologic pain does not protect one.
Pain can be persistent because of abnormal excitability in the nervous system. It can also be persistent from other mechanisms. For example, the pain of arthritis is due to chronic or persistent inflammation in joints and a reasonably intact nervous system sensing (the) inflammation.
If one took a hundred patients with low back pain and asked, "What are the mechanisms behind the persistence of their pain?", unfortunately, in the majority, we don't know. Factors other than either "nociceptive" - meaning tissue injury-related - or "neuropathic" pain are involved in many of those cases.
One might ask, if you have a painful area, why don't you just cut the nerves to it? Cutting nerves causes altered excitability and altered transmission in the nervous system and creates new forms of pain. In general, except for short-term situations, such as terminal illness, it's not useful to treat pain by cutting nerves.
DR. BORSOOK: At the global level, the major problem is availability of basic, cheap medications to provide pain relief. In 10 countries around the world, 86 percent of the world's morphine production is consumed.
By contrast, in underdeveloped countries not only are small quantities of drugs such as morphine available, but most countries around the world have laws to prohibit the use of morphine in the treatment of pain, acute and chronic.
In the United States:
Furthermore - and this is one of the biggest problems in clinical medicine - we don't believe our patients. If a patient is running around and they look normal and they say to you, "I'm suffering from pain," it's a very difficult thing to believe.
DR. BERDE: The cost of treating people with simple methods, namely, oral morphine, is really very low. The barrier is a conceptual barrier: confusion between the proper use of opioids and inordinate concerns regarding addiction.
These fears are seen with children, as well. Pain is difficult to measure, but there are methods - for an adult, by asking them with questionnaires, or for an infant, by using behavioral and physiologic measures. There are problems with measurement, but a child can be made comfortable just by methods similar to those used for adults.
In hospitalized children, fear and anxiety are a major part of their experience of pain. Creating a less terrifying hospital environment is a major part of relieving the distress of hospitalized children.
DR. BORSOOK: Pain, perhaps more than nearly any other clinical discipline, is going through a huge scientific revolution.
New pathways have been discovered that help in understanding components of pain that we hadn't an anatomical basis for, before. Autonomic problems associated with pain, such as altered appetite, problems with sleep, and so forth, (also) now have a neuroanatomic basis.
And very exciting now is the development of functional MRI and PET (magnetic resonance imaging and positron emission tomography) scans. We can see in humans where in the brain activity is taking place with both acute and chronic pain.
Pain is not just a sensory experience; it's an emotional experience and it can be devastating in terms of altering mood. For example, in cancer patients, a significant percentage are depressed, and when you treat their pain, those patients actually come out of their depression very rapidly.
Many drugs will come onto the market in the next couple of years. The new drugs that look as if they are going to be very good in pain treatment are drugs that affect glutamate transmission. We call these drugs "NMDA antagonists." Currently, morphine is the "standard" pain medication.
DR. BERDE: Addiction should be regarded as a behavioral or psychological syndrome of compulsive drug seeking. The outcome literature is very clear that in post-operative populations getting opioids, the incidence of addiction is no different from the general population. It's not created by making administration more generous or appropriate.
Q: When one can suddenly buy an over-the-counter medication that, up till now, was by prescription only, how has the possibility of abuse increased?
DR. BERDE: Most over-the-counter drugs are problems of abuse in a different manner. It's more an issue of the side effects of the anti-inflammatories, which are somewhat dose-related, that have increased risks in the elderly and people who have liver or kidney dysfunction. Twenty million Americans take anti-inflammatories on a regular basis, and perhaps eight to ten thousand have life-threatening gastrointestinal bleeding from them, every year. I'm not sure the solution is just to put them all on a prescription basis; I think it's better education of the public.
Q: In a spinal cord injury with paraplegia twenty years ago, treatment relieved greatly the intensity of the pain, but it is now back to even stronger than originally.
DR. BORSOOK: If you have pain in the periphery, it's not just there: The whole nervous system is involved. Depending on how long it's let to go and how much damage is produced, the nervous system will always remember that pain and the specificity of it - what it felt like and where it was.
When we look at chronic pain patients, there is abnormal electrical activity in pain pathways. Under normal conditions, there should be no spontaneous electrical activity.
It is unclear why, for example, in patients who have strokes involving part of the pain system, pain develops three, six months, maybe a year after the stroke. We think that abnormal connections develop in pain pathways to produce this chronic pain. This may be the reason why injuries to the spinal cord, even many years ago, can still produce severe, chronic pain states.
Q: What about the role of endorphins and can it be synthesized?
DR. BORSOOK: Endorphins are naturally-occurring opioids. The major one, beta endorphin, is secreted from the pituitary; and other natural occurring opioids are present in all of us. During painful states, there is a large induction of some of these (and) it's thought that the increase may protect the nervous system from further damage to neurons at a cellular level.
DR. BERDE: If your question is, can't we simply either give them to patients or find ways of having patients evoke them on their own: It's been tried a lot in clinical trials, and it's been reasonably disappointing. In most settings, it's not clear that natural endorphins injected into a patient offer a significant advantage over synthetic things, such as morphine. Many types of very investigational pain management - transcutaneous electrical nerve stimulation, or acupuncture, or, perhaps, hypnosis, or placebo phenomena - may involve eliciting the body's own natural pain-modifying chemicals.
Q: Is there any correlation between the intensity or the duration of some noxious insult and the likelihood of chronic pain?
DR. BERDE: The correlation is quite poor. Relatively minor injuries - some to nerve, some not - can trigger it; other people can have massive injuries and not develop persistent pain. The factors are very poorly understood.
Q: Talk about electronic blocking of pain.
DR. BERDE: Types of non-painful stimulation - rubbing a painful area, acupuncture, electrical stimulation of the skin - can produce pain relief in some settings. Something very simple, transcutaneous electrical nerve stimulation, is thought to work by eliciting events in the spinal cord that change the amplification of pain messages. But the literature on it is actually, in perspective studies, reasonably disappointing.
The same goes for implantable stimulators. Certain patients with very specialized problems benefit from implantable electrical stimulators, but it's a small percentage.