Priya is 31 years old, and is a homemaker. Although in good health, she suffered from occasional severe headaches, which were rather disabling. When her friends suggested a visit to the doctor, Priya refused, saying that she would rather suffer the pain than take painkillers. She had heard that painkillers had side effects, and was afraid to use them.
Her suffering continued for a few more years until the headaches became more severe. Eventually, she consulted a physician who diagnosed her with migraine, gave her some lifestyle advice and prescribed a medication that stopped the migraines from happening. Her symptoms got better, there were no side effects, and her quality of life was much improved since.
Why did Priya opt to suffer such pain? Why did she not see a doctor sooner? Was her fear of medications exaggerated? Are painkillers safe, and what should one know before using them?
These are questions that are common in everyday life. Doctors encounter variations of the above story every day. Some stories even involve overuse of painkillers and complications that follow.
To live free of pain is every man’s dream. Unfortunately, physical pain is common, and inevitable in our lifetime. This article discusses the phenomenon of pain, its intricate mechanisms, and the practical precautions to be taken when attempting to treat pain.
What is pain? How is it caused?
Everyone knows what pain is, but would rather stay away from it. Understanding the mechanisms of pain is important before trying to tackle it.
Pain is common after injury to any area of the body, due to local tissue damage and inflammation. When it occurs on the external surface of the body, it is easy to locate the source of pain, such as a bruise or a swollen joint. Pain can also occur from illness of the internal organs, where identifying the source might not be so straightforward.
All illnesses do not cause pain, and all pain is not due to illness. This raises a rather fundamental question: why do our bodies have built-in pain machinery? Would it not have been better to have a body that could not feel any pain at all?
While at first glance, it might seem quite an attractive idea to own a body that does not feel pain, it is quite evident that pain is an important part our of survival mechanism. Let us consider the example of a sprained ankle suffered while playing football. If there was no pain, we would not know that the ankle was sprained, and we would continue to run, damaging the joint further. Pain forces us to rest the joint for some time, during which the tissue heals itself.
Likewise, imagine that we place our hand inadvertently on a hot surface, for example, on an electric iron while it was plugged in. As soon as we feel pain, our hand withdraws by reflex – an automatic programmed movement that protects our body from more severe injury. In fact, such reflexes are so fast that the hand movement occurs even before we start consciously analysing where and why we felt the pain.
If heart attacks occurred painlessly, many people would not have made it to hospital, and would have perished from lack of timely treatment. The same logic applies to abdominal organs: the pain of an ulcer or appendicitis prompts us to visit the doctor who can diagnose the condition early enough, before complications occur. Some forms of ulcer or appendicitis can occur with no symptoms or with unconventional manifestations. Such patients often suffer from delayed diagnosis.
How is pain sensed by the body?
Pain is one of several sensations that our limbs can detect in addition to touch, temperature, pressure and joint position. For instance, when we close our eyes and pick up a coin from a wooden box, we can feel and identify the cold temperature of metal, the round shape and the contour of the coin’s surface. We can even estimate its hardness by checking whether pressure from our fingertip can compress it. But in the process if we accidentally touch the tip of a pin, we feel pain instead and withdraw our hand.
While the coin example above might seem unexciting at first glance, it illustrates how our body uses different types of receptors and nerve fibers to detect each of these sensations, which are finally pieced together by the brain, and the object is identified as a coin or a pin after correlating with stored memory of similar objects.
Pain is sensed by free nerve endings located in skin, linings of internal cavities such as peritoneum and pleura, walls of arteries, joints and the lining of the skull. Several internal organs do not have such nerve endings. For example, the inner lining of the intestine lacks pain receptors, and therefore we will not feel pain if a biopsy is taken or if the intestine is cut - even if it is done while we are fully awake. However, intestinal pain can still occur from stretching of bowel wall by gas, muscle spasm, inflammation and by lack of blood flow. On a similar note, the brain does not feel pain, though its coverings are pain-sensitive.
Pain receptors are triggered by mechanical damage (like a blow to the body), chemical damage (lactic acid from overexertion), or extremes of temperature. They generate a tiny electrical signal by a process called transduction. This electrical signal is then transmitted along the fast Aδ and the slow C nerve fibers till the spinal cord. From here, second-order neurons transmit the signals all the way up to the brain where it is finally decoded and perceived as pain.
For the sake of an experiment, if we submerge our hand in lukewarm water, it initially feels comfortable. At such cosy temperatures, the regular warmth receptors on our skin receive the gentle heat signals and reassure us that all is well. If we now slowly increase the temperature of the water, we start feeling pain at around the 45 degree C mark, prompting us to withdraw the hand. This is because temperatures in excess of 45 degrees will start being perceived as pain by the pain receptors, as it can injure tissue. This is yet another built-in protective mechanism against injury.
The degree of firing of pain fibers is somewhat proportional to the extent of tissue damage, which means we feel greater pain when the damage is more severe. Inflammation amplifies pain - a swollen joint is therefore more painful to move.
Pain need not always represent tissue injury. Muscle spasm and mild stretching of blood vessel walls can cause pain, such as what happened in Priya’s case above – a case of common migraine.
Sometimes, pain can occur in areas far away from the area of damage. This typically applies to internal organs that are designed to work silently throughout our lifetime – in such a way that under normal conditions, our brain has no idea about the existence or precise location of these organs.
For example, patients with gallstones may experience pain over their right shoulder, even though the gall bladder is located far away from that area. This is called referred pain, and is a way in which internal organs call for our attention when something goes wrong. These internal organs lack the localised pain response seen on the skin, but are able to communicate to us indirectly through such intriguing mechanisms. Referred pain occurs after the signals from the organ reach the spinal cord through the sympathetic nerves from the organ (which are not traditional pain fibers), and connect there with actual pain fibers that bring signals from a section of skin. As a result, the brain interprets that pain is originating from that particular area of the skin.
The pain of a heart attack, called angina is another example of referred pain: the heart is located deep inside the chest, while the pain may be felt in the neck, left side of the chest or left arm.
For the same amount of injury suffered, each of us perceives pain differently. Some feel more pain, some less, and for some, the pain lasts longer than others. This is because we are all wired differently, and there are numerous modifiers of pain that are not necessarily related to the injury site. Factors such as a low mood, anxiety and other psychological factors can make pain feel worse.
In fact, relief of anxiety is one of several mechanisms by which a placebo (fake treatment) reduces pain.
Chronic pain might be the only manifestation of mental disorders such as SSD (somatic symptom disorder) and no amount of medical testing will reveal any organic disease process. Illnesses like fibromyalgia, which causes chronic body pains in young adults, and functional dyspepsia, which causes ulcer-like pain in otherwise healthy people are more examples of painful medical conditions that do not have a demonstrable tissue source of pain.
Though sometimes superficially compared to the electrical circuitry of a house, the body’s nervous network is too complex to be predictable. A single nerve ending communicates with not just one, but three-dimensionally with numerous other nerves and glial cells, enhancing the complexity of the process. Certain types of pain can even get ‘imprinted’ in the brain, and therefore persist even after the injury has healed. Disordered neurological wiring and regulation is believed to be the cause of chronic painful conditions that affect large numbers of people worldwide.
Can we willingly reduce our own pain without medications?
This is where the story of pain gets really interesting. Our body has a built-in supply of painkillers, almost like we were born with an ampoule of morphine loaded in our brain. We have the amazing ability to relieve our own pain. How can this be possible?
Long before the discovery of modern pain medications, man and other fellow beings roamed the earth for thousands of years, their bodies being programmed for basically just one thing above all else: survival. Everyday life involved running from predators, climbing trees, falling and getting injured. Man could not compromise his own safety while sprinting for survival in the forest, even if there were minor injuries like a sprain or bruise that happened on the way. Using these built-in mechanisms, man was able to temporarily suppress his own pain and keep running until he reached the safety of his cave.
The mechanisms for such natural pain relief are two-fold. First, there is a descending pathway of nerve fibers from the brain that is exclusively concerned with pain relief. These fibers originate in the periaquedutal gray matter and Raphe nucleus in the brainstem, travel down through the spinal cord, and connect with the same pain fibers that pick up the pain signals in the first place. These descending nerve fibres release morphine-like substances (endorphins) at their endings within the spinal cord, which blocks the receptors on the pain fibers nearby, just like an IV injection of morphine would do. As a result, the pain signals arriving from the periphery get arrested halfway - at the level of the spinal cord - and pain is not detected by the brain. This temporarily blocks the pain of injury, which allows the body to transfer to a safe zone.
The so-called placebo effect, where people report pain relief even with a dummy medicine, has been shown to be partly due to stimulation of the brain’s endorphin release by a strong belief and expectation of pain relief. Endorphins, short for ‘endogenous morphine’ are the body’s natural painkillers. An elegant experiment using PET scans conducted by University of Michigan demonstrated how the brain was able to produce endorphins at each point where a person expected a pain injection, and believed he got one - even when a fake injection was used. Others have shown that placebos fail to work when the opioid receptor is blocked using Naloxone, confirming that endorphins are involved with the process.
The second mechanism is the gate-control theory of pain, originally proposed in 1965 and modified since. It is best illustrated by the following example.
Let us imagine we are trying to drive a nail into the wall using a hammer. If the hammer accidentally hits our finger, we quickly give the finger a good shake and then massage it. This temporarily reduces the intensity of pain. How does this happen? Gate control theory states that rubbing the area of pain and moving the joint generates friendly sensory signals that rapidly travel up to the same region of the spinal cord that receives the pain signals from that particular location. By interfering with the upward transmission of the slower pain signals that arrive marginally late, these touch signals essentially ‘close the gates’ on pain, reducing the amount of pain perceived by the brain. This is thought to be the basis for massage, acupuncture and TENS (transcutaneous electrical nerve stimulation), all of which are effective in reducing local pain when delivered by experts.
Pain-relieving balms containing menthol are also believed to act through this mechanism, by stimulating the TRPM8 ‘cold’ receptors on skin, generating a sense of coolness that competes with pain signals at the level of the spinal cord.
What are painkillers?
These are medications that reduce the intensity of pain, also called analgesics. From the lowly but effective paracetamol to the supremely potent morphine, analgesics comprise a whole spectrum of medications. Analgesics also include powerful anti-inflammatory agents like Prednisone which belongs to the family of steroids, the once-popular Aspirin and the so-called NSAID’s (non-steroidal anti inflammatory agents) such as Ibuprofen and Diclofenac. In addition, there are the Cox-2 inhibitors like Celecoxib, and stronger agents of the opioid category such as Codeine, Tramadol, Fentanyl and Morphine.
Along with painkillers, adjuncts are also sometimes used, including agents such as anxiety-reducing agents and other drugs that work on the nervous system such as Tricyclic Antidepressants, Venlafaxine, Pregabalin and Sodium Valproate. These are effective when used in combination with traditional pain medications in select cases.
What are the side effects of some commonly used painkillers?
As several painkillers are available without prescription over the counter, a basic understanding of their safety profile is worth a mention, while a comprehensive review is not the objective of this article. Undue anxiety about side effects is common, and leads people to suffer pain needlessly - as in Priya’s case above. The topic of side effects has been covered at length in my earlier article.
By far, the most common analgesic used is paracetamol or acetaminophen. Among the safest medications invented by man as long as it is used within recommended doses, paracetamol is also abused in the western nations as an agent for committing suicide. Its property of consistently causing liver failure in massive doses has earned paracetamol this dubious reputation. It should not be taken along with alcohol as the risk of liver damage is high. At a dose of under 4 g per day in healthy adults, paracetamol does not cause injury to internal organs, and is the safest pain killer from the standpoint of the stomach.
The next most commonly used agents are the NSAID’s, which have the property of causing stomach irritation at higher doses taken over long periods of time, particularly in the elderly and when taken along with other stomach irritant medications such as aspirin. Best taken after food, these agents are strong, safe and effective agents for pain, and rarely cause harm when taken for a short periods of time in the right doses by people in otherwise good health. Prolonged use occasionally leads to kidney damage and peptic ulcers, sometimes causing internal bleeding. Aspirin is used less commonly now as a pain-relieving agent due to its tendency to cause stomach ulcers.
Opioids are the strongest painkillers available, and must only be taken by prescription. Side effects include constipation due to their slowing effect on gut movement pattern. Other adverse effects are nausea, sleepiness and dependence.
The WHO analgesic ladder:
Depending on the severity of the pain and the underlying condition, WHO has devised an analgesic ladder to help guide doctors and patients to achieve safe but effective control of pain. This historic document, carefully crafted 30 years ago for treating cancer pain has streamlined the management of pain worldwide, helping to reduce the suffering of millions of patients suffering from chronic pain.
Essentially, it recommended three tiers of medication for pain of increasing severity. The lowest rung of the ladder consists of simple analgesics like paracetamol, while the higher rungs involve more powerful medications and interventions. Modified and adapted for various types of non-cancer pain and supplemented with newer pain-relieving modalities and drug-delivery systems in the past 30 years, the ladder remains relevant to this day.
The fundamental principles of the ladder are worth commenting on. First, the patient’s pain must be kept controlled using the least effective dose of oral medications given at recommended intervals for the shortest duration of time possible. Second, pain medications must be administered after assessing the patient’s reported pain severity using standardised scales, rather than the provider’s guess of how much pain the patient has. It is noteworthy that unlike blood pressure or haemoglobin that are tangible values, there is no lab test that measures the severity of pain - hence the patient’s perception has to be given due respect and therapeutic consideration. Third, customisation is required for each patient, rather than a one-size-fits-all approach, as each patient feels and responds to pain differently.
In summary, although intrinsically a protective mechanism, pain is an unpleasant symptom that warrants an evaluation for its cause. Once a diagnosis is made, the objective must be to reverse the disease process as far as possible, at the same time reducing suffering by administering adequate pain relief. Treatment of chronic pain requires the collective effort of a multidisciplinary medical team along with the family members of the patient who value the patient’s comfort, dignity and safety. Caregivers’ attitude towards pain is as important as their technical knowledge. While side-effects can occur over the long term, short term use of pain medications under a doctor’s supervision is generally safe, and can reduce needless suffering in the interim. Skilful treatment of pain can add priceless hours and days of good quality of life.
For further reading
(The author is a senior consultant gastroenterologist and deputy medical director, Sunrise group of hospitals)