Shooting the Messenger


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Pain is not a welcome sensation but it has its place in serving as an early warning system. This is the first chapter in a book on knee osteoarthritis "Knee Deep in Pain" and discusses how pain is triggered and how we feel it.
Zafar Hayat Khan

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Shooting the Messenger

  1. 1. 1 Of 16 Knee Deep in Pain – A Book by Zafar Hayat Khan CHAPTER-1 Shooting the Messenger Figure-1. Athena. ©2010-2012 Juraj Nevolnik
  2. 2. T 2 Of 16 Knee Deep in Pain – A Book by Zafar Hayat Khan he gods were running out of amusing things to indulge themselves with. Poseidon was getting tired of slapping mermaid tails and Zeus had run out of targets after destroying much of the forest with his bolts of lightning fired from the top of Mt. Olympus. Feeling a bit mean spirited the brothers plotted to have some serious fun. They decided to hold a special give away. They announced they would hand out gifts, offering four; Beauty, Brains, Drama and the fourth was a mystery item labeled ‘P’. The only rule was, while anyone could pick one of the four and walk away with it, if someone went on to take two they must accept the mystery gift as well. Narcissus happened to glance up from the edge of the still pond where he was sitting admiring his looks, and mumbled: “I am already beautiful, who needs brains; they are boring, I have no interest in mystery, but… Summary hhhmm… I could surely use some Pain is not welcome but it drama…”. serves a purpose. This He took that one. chapter outlines a brief history and general Big surprise there! discussion of pain. Aphrodite came along and knowing that brains were so overrated snapped up Beauty, and quickly departed fully aware of the trouble the brothers were capable of. Athena was passing by and decided she was definitely interested. She selected Beauty and of course without wasting a breath also immediately picked up Brains. Bamm! Zeus roared: “Athena, you and your sisters will forever live with Pain”. Unwittingly she had been awarded the mystery gift ‘P’. Athena complained loudly but no one heard. She tried to console herself by assuming the two gods were
  3. 3. 3 Of 16 Knee Deep in Pain – A Book by Zafar Hayat Khan talking about sharing life with a man, which can bring unbounded misery all on its own. Finished with their particularly mean prank, one brother went back to chasing mermaids, while the other flew back up to the throne on the mountain amidst smoldering remains of previously zapped tree tops. Both brothers completely oblivious of the damage their prank was about to do. Narcissus was too busy with “Mmwahh… Mmwahh” kissing his own reflection in the pond. It is said he stars in several soaps on daytime American TV. Judging by how long some of the soaps have been airing, there might be some truth to that rumor. One thing is certain. Women’s pain is real. Even though it has taken society a very long time to acknowledge it, primarily because women were expected to suffer in silence, and they did. Historically what carried more weight was pain in a ‘man’. Something else has changed. We will see that later toward the end of the chapter in a conversation about some special receptors. Claudius Galen (129-199 A.D.) would know pain when he saw it. He was the Roman physician officially appointed to taking care of gladiators.1 Given the cuts, bruises, bludgeoning, hammering, stabbing and piercing these combatants endured in the arena there would be no dearth of material for Galen’s study on treating pain. A picture of a real life gladiator can be painted from findings of two pathologists at the Medical University of Vienna 2 working on an archaeological dig in Turkey. They examined 67 bodies with painstaking detail in what appeared to be a cemetery where gladiators were buried. Marks and scars on the bones of skeletons indicate healed wounds on these professional fighters who were expensive to maintain for their nourishment, training, and medical treatment. Most of
  4. 4. 4 Of 16 Knee Deep in Pain – A Book by Zafar Hayat Khan them were young, in their 20s and 30s and since this was a profession, perhaps adequately lucrative, they repeatedly returned to combat until they were either killed by another combatant, or were so badly wounded someone had to finish them off, possibly an associate, fulfilling a mutual pact of mercy. Do individuals experience, and express pain differently? Apparently pain expression does have predictable religious, cultural and ethnic elements to it. If you grew up in a first generation immigrant family in North America you would have been exposed to some confusing signals about how varying degrees of pain are expressed. For instance in some cultures, middle aged and sometimes even younger people will groan when sitting down or getting up. Figure-2. Pain everywhere. Pollice Verso. (Thumbs Down). Jean-Léon Gérôme. Phoenix Art Museum 3 For many of us it would sound like the person is in pain but that may not be the case at all. For instance, in a study published in 1991, female Mexican patients moan when uncomfortable but it may not mean they are suffering from pain. Nevertheless,
  5. 5. 5 Of 16 Knee Deep in Pain – A Book by Zafar Hayat Khan nursing staff view them as whiners who have a low tolerance for pain.4 Such lack of awareness of cultural differences can create peculiar situations in the delivery of healthcare. In 1993 authors of the same study looked at two populations of women patients, one Anglo American and the other Mexican American, and asked them to use the McGill Pain Questionnaire to evaluate pain they were experiencing after a cholecystectomy. Multivariate analysis of variance (MANOVA) was employed to see if there were any significant differences in the two groups on any measures of pain. There weren’t any. Nursing staff were then asked to rate pain experienced by patients based on the two groups of women’s responses. As it turned out nurses assigned more pain to Anglo Americans and judged the Mexican American women’s pain to be less.5 In the paper ‘Culture and Pain’, 6 Gary Rollman quotes an article from the 1985 issue of Clinical Journal of Pain “..Scandinavians are tough and stoic with a high tolerance to pain; the British are more sensitive but, in view of their ingrained ‘stiff, upper lip’ do not complain when in pain; Italians and other Mediterranean people are emotional and overreact to pain; and Jews both overreact to pain and are preoccupied with pain and suffering as well as physical health.” 7 Quoting another study Rollman writes about how some Christians, in an attempt to identify with Christ’s own pain and suffering, embrace pain either when it is accompanied by disease or inducing it by “selfchastisement” as in stigmata.8 According to the Institute of Medicine, well over a 100 million American adults—more than the total affected by heart disease, cancer, and diabetes combined, suffer from chronic pain at a cost of up to $635 billion each year in medical treatment and loss of productivity.9 In his testimony, Dr. Philip A Pizzo, Dean of the Stanford University School of Medicine as well as
  6. 6. 6 Of 16 Knee Deep in Pain – A Book by Zafar Hayat Khan Professor of Pediatrics and of Immunology and Microbiology, called the magnitude of pain in the United States ‘astounding’, with more than 116 million Americans suffering from pain that persists for weeks to years. This data does not include children, individuals in nursing homes or chronic care facilities, prisons or the military, making the impact even more significant. Authors of the study, released in 2011, argue for ‘relieving pain’ to be given a national priority given the toll it takes on human lives and social consequences, not to mention the hard dollar costs. Figure-3 "Kaibo Zonshinzu Anatomy Scrolls (1819) 11 There is also a gender element in sensitivity to pain. 10 Women are more frequent sufferers, but seek help more readily, and as a result recover more quickly from pain. They are also less likely to allow pain to control their lives. Unfortunately, biology and skeletal differences make women more prone to pain, and they also feel it more acutely than men. A constant and unavoidable irritant in women’s anatomy is the Q-Angle, covered in the chapter Care to have a joint? Other causes of pain may be explained by hormonal differences. When researchers injected male mice with estrogen, a female hormone, the result
  7. 7. 7 Of 16 Knee Deep in Pain – A Book by Zafar Hayat Khan was a lower tolerance for pain. However, female mice when injected with testosterone, a male hormone, resulted in the female mice exhibiting a higher threshold for pain. So, what is pain? Galen of Pergamom, the gladiator physician, who was a famous anatomist and also served as personal physician to the Roman emperor Marcus Aerilius, distinguished three types of nerve: "soft" nerves, "hard" nerves, and pain nerves, and believed the brain was central to sensing pain. His contributions to medicine are memorialized with naming of the ‘vena Galeni’ or ‘vein of Galen’; one of the larger vessels responsible for draining the anterior and central regions of the brain.12 Up until Galen most of existing medical knowledge and philosophy did not connect pain to the brain and dominant thinking continued to identify pain as an emotional state. Plato (c. 427 BC – c. 347 BC), the prominent classical Greek philosopher, and founder of the Academy in Athens, thought that the heart and liver were where the sensation of pain was felt and it arose not only from peripheral sensation but could also be an emotional response in the soul in the heart. 13 Plato’s student, Aristotle, did not believe the brain had much to do with the sensation of pain either. He was of the opinion that pain was the result of evil spirits entering the body through injuries. Hippocrates, known as the father of medicine, was of the view that pain resulted from imbalances in the vital fluids. 14 IbnSina of Persia [980-1037], a great Muslim physician known in the western world as Avicenna, wrote extensively about the brain as a center for pain sensation. He expanded Galen’s four pain classification types to fifteen.15 Many of the terms used by IbnSina in his classification are strikingly similar to those used in the 1975 McGill Pain Questionnaire16 developed by Ronald
  8. 8. 8 Of 16 Knee Deep in Pain – A Book by Zafar Hayat Khan Melzack in Canada. Earlier, in 1965 Dr. Melzack had introduced the Gate Control Theory at MIT. It was not until the mid 17th century when the brain became center stage for pain sensation. René Descartes (1596–1650), a philosopher, broke from established religious thought about pain being punishment from God, and theorized that it had nothing to do with the soul but instead there was a direct mechanical pathway from the site of the injury on the human body to the brain.17 Defining pain is not easy and explaining it is not that simple. Scientists and researchers still struggle with identifying what it is. What makes this topic a moving target for definition is the variability of individual experiences in the severity and duration of pain. The International Association of Pain describes it as an “unpleasant experience”, both sensory and emotional.18 But some people can feel pain when there is no apparent injury while others do not feel it even when they are hurt. And still others who have had a limb amputation continue to feel pain in the limb that is missing. 19 Apparently, after the amputation, nerve cells rewire themselves to continue to receive pain messages. If the brain is part of the pathway for pain sensation does it mean it could be mobilized to combat pain? The Gate Control Theory 20 put forth in 1965 by Ronald Melzack who specialized in phantom pain at McGill University in Montreal, and Patrick David Wall, a leading British neuroscientist, provided further insight into the pain-brain connection. According to this theory, pain messages reach neurons in the ‘substantia gelatinosa’, the gelatinous caps in the rear dorsal horn of the spinal cord, and from there the messages are sent to the brain (Figure-4, left panel) through a gate mechanism which is held open for rapid transfer of information.
  9. 9. 9 Of 16 Knee Deep in Pain – A Book by Zafar Hayat Khan Under normal conditions substantia gelatinosa also receives messages from the brain. Further, according to the theory, messages from the brain may “…make it possible for central nervous system (brain) activities subserving attention, emotion, and memories of prior experience to exert control over the sensory input.” After the first sensations of pain are registered at the brain, it is possible to modulate the severity by sending impulses to the gate in order to close it (Figure-4, right panel). Thus messages from the brain could serve to offset or limit the severity of pain at the spinal cord before pain sensation is transmitted to the brain. Not only the brain, but sensory inputs like rubbing or scratching the vicinity of the pain source can help close the ‘gate’ to prevent Neurons are self sufficient or attenuate pain messages nerve cells that conduct from reaching the brain. What electrical impulses back and forth in the body. A vast makes this theory particularly majority of them are found in the brain. They die with age interesting is that it is based on the differences in the types and disease. of nerve fibers. Ones that carry ‘pain’ impulses are being blocked by those that carry ‘touch’ sensations. Scientists know about this difference in nerve structure and function.
  10. 10. 10 Of 16 Knee Deep in Pain – A Book by Zafar Hayat Khan Figure-4. Model of Gate Control Theory. © 2012 Nouvelle Sante. Knee Deep in Pain. Pain happens to be relayed by very narrow diameter nerves and travels at a slower speed, about half a meter per second.21 Known as ‘C’ fiber nerves they also take longer to recover in between firing of impulses; this keeps the maximum to 250 impulses per second. In comparison, the ‘touch’ nerve, called the ‘A’ fiber, is wider in diameter, travels at up to 130 meters per second and shoots at the rate of 2,500 impulses per second. There is one other difference; ‘C’ fibers are uncoated while ‘A’ fibers are sheathed within a ‘myelin’ hose structure, helping in delivering noiseless messages that travel along highly focused paths. The speed and protection of transmission make the ‘A’ fiber a very important ally against pain. So, if you were a pain researcher who would you pick as your ‘best friend forever’? Paris Hilton, of course. 22
  11. 11. 11 Of 16 Knee Deep in Pain – A Book by Zafar Hayat Khan When you accidentally touch the hot surface of a toaster in trying to get your bread out in a hurry, it is the ‘A’ fiber over which this information travels to the spinal cord from where a motor neuron shoots a stimulus to the muscles in your arm and hand to withdraw instantly. If it were not for the ‘A’ fiber your fingers would be toast. Dorsal Horn The dorsal horn is found towards the back of the spine through all levels of the spinal cord; cervical, thoracic, lumbar, and sacral. This area receives information from the rest of the body in ‘substantia gelatinosa’ cells at the cap of the horn. These sensations include touch, vibration, temperature and pain. These sensory messages are then relayed to the brain. Please see Appendix for more information on substantia gelatinosa. Just so they are not left behind from the ‘pain inflicting party’, prostaglandins, membrane associated lipids that activate whenever, and wherever there is a problem, can cause pain by direct action upon nerve endings. Even at low concentrations, they markedly lower the pain threshold thereby increasing sensitivity. Lowering of the threshold can cause even normally painless stimuli to become exaggerated. When produced within the central nervous system, they sensitize perception to painful substances. Pain is thus induced both at the site and at the central nervous system, where signals are processed.23 Prostaglandins are covered in more detail in the chapter 10: Veni, Vidi, Vici. When the Huns invaded China, the dreaded Shan Yu of Hollywood, and leader of the ruthless warriors, claimed he will kick a certain ruler’s behind before long. Little did he know that it would be somewhat difficult since that certain part of the emperor’s anatomy was a bit preoccupied. Being that he was sitting on pins and needles, not worrying himself sick, but in fact relaxing his mind to think clearly and to devise new strategies, such as bringing Fa Mulan from Disney on board to fight the
  12. 12. 12 Of 16 Knee Deep in Pain – A Book by Zafar Hayat Khan invaders. Not surprisingly the people who built the Great Wall also knew a thing or two about gates. The pain relief practice that has been used, and has thrived, in China for over 2,500 years, some say 8,000 years, is acupuncture. It remains an an unfathomable mystery, how, several thousand A name for Gate Control years ago, without advanced Theory does not exist in diagnostic and analytical Chinese, but if it did it would be called “chowmen kumchi Equipment and billion dollar labs, luwen” some geniuses in China figured out 閘門控制理論.24 a connection between nerves, pain The Chinese name for acupuncture happens to be and relief. 针刺 (pronounced chen su, written zhen jiu). It translates as ‘needle thorn’ on Google. Pain Receptors are found at the receiving end of the neuron’s pathway for communications at the tips of dendrites; tentacle like nerves. They are found throughout all tissues of the body, including skin, muscles, joints, and organs. The proposed mechanism used by the gate control theory, validates ‘zhen jiu’ in a fascinating manner. 25 Inserting needles in the skin in selected areas and then twirling them stimulates the two sets of nerves, containing ‘A’ and ‘C’ fibers. Some of the initial pain sensation gets through to the brain through the spinal cord possibly because the ‘A’ fiber nerves have not been poked yet. Once they get stimulated they start reaching the spinal cord much faster and with higher frequency than the pain carrying impulses, in effect closing the gate. At this stage pain messages are unable to get through to the brain, in a sense, bumping up against the closed door. This is like a “who’s your daddy now” moment for the touch sensing ‘A’ fiber nerves standing at the gate looking down at the pain sensing ‘C’ fibers. The gate control theory does not explain how, pain remains absent for several hours after acupuncture. And for itself, acupuncture has not done well in studies 26 showing some benefits of statistical significance but not enough for clinical
  13. 13. 13 Of 16 Knee Deep in Pain – A Book by Zafar Hayat Khan relevance and pain reduction “independently of the psychological impact of the treatment ritual is unclear.” 27 A 2005 study in JAMA concluded, “Acupuncture Treatment No More Effective Than Sham Treatment In Reducing Migraine”.28 Even if acupuncture was as effective as supporters say, it still remains one of the pain remedies and another weapon against the ‘messenger’. But we are still far from a cure. Here we will return to the gender-pain connection and see if men and women respond differently to medications. Well, at least one remedy appears to be more effective for women than for men. It has been discovered that pain killers that bind to kappa-opioids receptors work better in women than men. Researchers are not sure if it is a woman's estrogen that makes them more effective, or is it a man's testosterone which obstructs the mechanism for ‘kappa-opioids’ pain relief in men. But any discussion really becomes strictly academic as the person feeling the pain is less concerned about its definition and more about how to seek relief. There is probably no mortal out there who has gone through life without experiencing pain. In fact, in the U.S., chronic pain is responsible for more disabilities than heart disease, stroke, cancer, and AIDS combined. 29 Regardless of where pain originates, prevailing scientific thought tells us the sensation is communicated to the spinal cord, from where it is transmitted to the brain to be registered in memory.30 From there, as a response, signals are sent to facial muscles where a visible reaction is conveyed and to other muscles that may help in taking corrective action where the original stimulus that triggered the pain occurred. At the same time messages may be sent to muscles that control the vocal chords to complain about the pain. It would be safe to assume unless our brain tells us we have pain we will never know about
  14. 14. 14 Of 16 Knee Deep in Pain – A Book by Zafar Hayat Khan it. Above all, pain is a crucial feedback mechanism. Without registering pain we would not be able to stop and remedy whatever we are doing that triggered the stimulus in the first place, possibly causing irreparable harm to the body. Arguments against the value of pain as a signaling and messaging mechanism 31 will continue to place emphasis on finding new and novel ways of ‘shooting the messenger’ while ignoring root causes. In this, modern medical treatment has diverged from ancient practices. Where pain was, in many cases, supposed to be a necessary part of sickness and salvation, the actual cause of the affliction was given priority, and any cure, medical, therapeutic, or magical focused on the problem and not the pain. After all, Attila the Hun, in his lecture to prospective MBA students, advocated shooting the person who did ‘not’ deliver bad news.32 But it may have been tyrants like Attila the Hun, the real one, who can be credited for the priority shifting from curing the disease to the treatment of pain. Imagine being a personal physician for a ruler. Every time you stepped out to purchase herbs and ingredients to treat some royal illness, people in the market place bowed out of respect and gave you preferential treatment. After all you were responsible for the king’s continued health. You were clearly distinguishable because of the tall pointy hat you always wore in public. When the chemist would try to advise you the ingredients you are shopping for are not related to the malady you were supposed to be treating, you would mutter under your breath you don’t know my life. They don’t know how hard you get whacked ‘upside your head’ when the king squirms in pain. And the throbbing lumps make your head look like a potato with a
  15. 15. 15 Of 16 Knee Deep in Pain – A Book by Zafar Hayat Khan personality which you don’t want others to see. Hence the tall pointy hat! Now you need pain medication both for yourself and for your liege. For your own welfare and self preservation; ‘better to treat the pain than the problem’; and in your defense, we understand. Finding an actual cure for many of the diseases is just not that simple, if at all possible. Taking care of pain is only one aspect of treatment. If the root cause is not addressed, pain will return. The longer it takes to treat the source, the higher the chances the person will eventually become a chronic pain patient. For citations please see pages 253 through 257 in Bibliography.
  16. 16. 16 Of 16 Knee Deep in Pain – A Book by Zafar Hayat Khan Appendix Spinal chord – gray matter Wikipedia User: Polarlys. CCA 2.5 Generic license. Pain and other noxious information is transmitted through myelinated delta-‘A’ and unmyelinated ‘C’ afferents to the substantia gelatinosa in the dorsal horn, mostly to lamina II. SG neurons exhibit a variety of excitatory and inhibitory synaptic responses that range in duration from milliseconds to minutes. The sensory received at the SG is modified and integrated regulating the outputs of projection neurons located in lamina I, IV–V. 33