An Anatomy of Pain: How the Body and the Mind Experience and Endure Physical Suffering

by Abdul-Ghaaliq Lalkhen

Lalkhen states that his mission in this book is to explain pain in all its forms: pain from physical trauma, cancer pain, and pain that appears to continue in the absence of any physical damage.

We have vacillated over the centuries between advocating that pain should be aggressively treated and believing that pain is necessary and important to the curing of the condition or an integral part of the treatment being given.

In the 1990s and 2000s many professional healthcare bodies representing surgeons and anesthesiologists encouraged hospitals to provide specialist acute pain services. Pain was labeled “the fifth vital sign,” and aggressive pain management was considered both clinically important and a fundamental human right. The other four vital signs are temperature, heart rate, blood pressure, and respiratory rate. However, the zealous pursuit of this goal and linking pain relief to hospital quality outcome measures may have contributed to the opioid epidemic.

Pain is an alarm system. When you sustain an injury, the traumatized tissue releases and attracts chemicals called inflammatory mediators. The aim of these substances is to heal the damaged tissue, but they also play a role in triggering the pain alarm. The release of chemicals such as hydrogen ions, potassium ions, bradykinins, and prostaglandins stimulate the harm-sensing receptors (nociceptors) in the tissues. The damage signals also reach the parts of the brain that can release substances that cause pain relief (naturally occurring opioids and cannabinoids), but these descending inhibitory pathways are poorly understood.

But pain is a very complex biological alarm system. It is biologically ancient, with pathways that are hardwired into multiple areas of the brain, and it is not as specific a guide to danger as we like to think it is. Dysfunction of the organs, for example the heart or the pancreas, results in poorly localized pain to the left arm and the middle of the stomach, respectively. The specificity of pain as a symptom is therefore often overestimated.

However, our expectations as patients, and sometimes as doctors is based on a philosophy that aims to attribute a complex condition to a problem within a single structure, such as a facet joint; this philosophy is rooted in the old Cartesian model of pain, and doesn’t serve us well.

2 types of fibers: Myelin-sheathed nerve endings (A delta fibers) conduct electricity faster than their thinner, uncovered counterparts (C fibers); the faster signals from the A delta fibers make you instantly remove your hand from a hot object, whereas the slower fibers produce the sensation that teaches you not to touch the hot object again.

Once these fibers have conveyed information to the first and second layers of the dorsal horn, glutamate is released from the dorsal horn nerves when the electrical signal generated from nociceptor activity reaches it. This opens doors within the spinal cord, sending a message to the brain about what has happened. The graver the injury, or the more times it is inflicted, the more keys are made available and the more doors are opened, resulting in more information being sent from the spinal cord to the brain - a phenomenon called wind-up, which contributes to the persistence of pain even when the injury has healed.

5 superhighways of information ascending to the brain from the spinal cord: the spinothalamic tract (the “where is the problem” pathway), the spinoreticular and spinomesencephalic tracts (triggering arousal, emotion, fight-or-flight instincts and activating motivation circuits in the brain that determine how we behave toward injury based on previous experience), and the cervicothalamic and spinohypothalamic pathways (controlling the regulation of hormones)

Treatment of pain: Interestingly the same brain chemicals we try to increase with medication when treating depression (serotonin and noradrenaline) are fundamental to the activation and functioning of these pathways.

How pain affects the body: As well as altering a patient’s behavior, pain activates hormones and chemicals that affect the body’s ability to heal. When we are stressed we naturally secrete cortisol, a hormone that breaks down protein to make sugar available for muscles to use as energy, fueling flight from our plight. Untreated pain results in an increase in this hormone, with the effect that it begins to break down muscle, leading to loss of muscle mass, which affects breathing and results in delayed wound healing.

How the mind modulates pain: Example: We know that the release of adrenaline as a response to stress can cause an increase in muscle tension and that the increase in muscle tension reduces blood flow (and therefore oxygen supply) to the muscle, which then releases bradykinin in response to being starved of oxygen; the bradykinin then activates more harm-sensing receptors. Anxiety and stress, therefore, which we would regard as psychological constructs, influence the pain experience on a biological basis.

Depression and anxiety play a role in the experience and report of pain. Catastrophizing is a psychological construct that consists of excessive rumination, magnification, and helplessness in the face of adversity and involves extreme negative thoughts about one’s plight. A higher level of catastrophizing, and consequently feeling a lower sense of control, is an important predictor that a patient will experience severe acute pain or develop chronic pain, when pain persists beyond what would be medically expected.

Expectation plays a role. The author advises doctors to tell patients a realistic number out of ten for their pain after an operation, so that they don’t wake up with an expectation of zero pain and then interpret any pain as something “wrong” and catastrophize, which can increase the likelihood of chronic pain.

Chronic pain: Chronic pain can in part be due to the development of pain-related fear, when patients adopt an approach to managing persistent pain by trying to avoid activities that might cause an increase in pain. Patients who have undergone surgery or experienced trauma and who have high levels of catastrophizing, for example, may find it difficult to rehabilitate because of this psychological construct. The longer someone has experienced chronic pain, the harder it is to treat.

In Western industrialized societies there is a tendency to divorce the emotional component of the pain experience from the physical, reducing pain to a dualistic Cartesian view where the mind and the body are separate, where we exist as an animal with physical processes, and a psychological being exists outside of us, ethereal and esoteric. This is why we have difficulty understanding pain in the absence of tissue damage and why we also struggle to understand diseases such as depression and psychosis, which are due to dysfunctional brain neurotransmitters but which our current medical technology (MRI scans, blood tests, electrocardiograms, etc.) cannot definitively measure.

Fibromyalgia and other, similar conditions such as chronic fatigue syndrome, which fall under the umbrella of “central sensitivity syndromes,” may be triggered by certain types of infections, for example Lyme disease or viral hepatitis. Psychological stress, including from deployment to war, has been associated with the development of conditions such as fibromyalgia. There appears to be a mixture of genetic factors that renders an individual vulnerable to the development of central sensitivity syndromes.

Patients with chronic pain may have different enzymes that predispose them to developing persistent pain. There is an enzyme that breaks down the neurotransmitters noradrenaline and serotonin, chemicals involved in both mood and pain, and people who develop chronic pain have been found to have abnormal versions of these enzymes; they end up with lower levels of these pain-relieving and mood-uplifting chemicals. We also think that psychological factors (thoughts and feelings) can cause physiological changes, particularly changes in brain chemistry, which might lead to a person’s developing chronic pain. Nociceptors are also differentially sensitive, and having more sensitive ones may predispose someone to chronic pain.

Drugs: there is no drug in our current armory that will completely abolish the experience of pain - apart from local anesthetics that can temporarily block all transmission of electrical signals. Local anesthetics are not suitable for long-term use, however; they are limited in their duration of action when administered as a single injection and require ongoing infusions. Local anesthetics cross the membrane of the nerve and blocks the sodium channel of the nerve from the inside, which means it cannot fire.

Ketamine is often used now in trauma because it does not cause a massive drop in blood pressure like other anesthetic agents, such as propofol. It produces what is called dissociative anesthesia, where you are unresponsive to pain but completely aware of your surroundings.

Anti-inflammatories are often given in pain management. However, are difficult to give to patients who haven’t eaten because blocking the prostaglandins generally stops their protective function in the lining of the stomach, allowing acid to potentially eat through the stomach lining, causing an ulcer with resultant bleeding or a hole in the intestine. Anti-inflammatory medications also affect the stickiness of platelets, which are necessary for clotting, and therefore pose a risk for increased bleeding. Nonsteroidal anti-inflammatory drugs, or NSAIDs, may inhibit bone formation because they inhibit prostaglandin formation.

Acetaminophen (Tylenol) is an oddity as a pain-relieving medication - widely used but, again, poorly understood. Paracetamol is a fever-lowering drug primarily and a very mild painkiller that we think works on cannabinoid receptors (receptors involved in mood, appetite, pain, and memory, which are widely found in the body) or possibly on a mystery enzyme. But the truth is we don’t really know how it works. It was accidentally discovered when looking for a cure for intestinal worms.

Opioids, interestingly, may affect perceived pain due to their effect on the emotional component and individuals’ reaction to pain, blunting the ability to actively manage or think about the sensations they are experiencing, rather than by blocking nerves or reducing inflammation. These started out as pain management for cancer care, and there was less long term risk there because those were terminal cases. However, when opioids began to be used for non-cancer care, many long term effects, including dependency, became evident. In fact, in the 1980’s, it was widely thought that opioids weren’t addictive. The evidence base for this assertion was the two small retrospective publications by Foley from 1981 and 1986 on studies conducted with cancer patients. The author believes we have good evidence for the use of opioids in acute, but not chronic pain.

Antidepressants are sometimes used in pain management, because descending inhibitory pain pathways and depression act through some of the same mechanisms.  In order to activate the descending inhibitory pathways and reduce the patient’s perception of pain, the drug needs to be able to raise both serotonin and noradrenaline, so older antidepressant drugs are often used for this instead of the newer class.

Doctors also use drugs such as gabapentin and pregabalin to treat pain, borrowed from the world of epilepsy. As with antidepressants, there is considerable crossover in the biochemical disturbances that cause epilepsy and chronic pain. In neuropathic pain the disturbance is in the orderly arrangement of channels within a nerve. When you damage a nerve in this way it expresses sodium channels in a haphazard fashion, resulting in the firing of the nerve in a spontaneous and unprovoked manner.

Other treatments: The author advocates for use of a relatively new technology for managing chronic pain called spinal cord stimulation (SCS). Early version induced tingling to replace the pain sensation, but newer versions use a higher frequency and don’t induce tingling. The idea is that this high-frequency current changes the balance of misbehaving nerves in the spinal cord. If we think of the nerves as a class of children, the current empowers those children that behave well by increasing their power, which in turn exerts an inhibitory effect on the badly behaved children and therefore makes the class overall seem better behaved. The tingling-based therapies, on the other hand, create a distraction outside of the classroom, taking attention away from the badly behaving children.

Questions:

How did you find the author’s tone in this book? It has been called both compassionate and condescending by different readers. How do you feel about passages like:

“With chronic pain, however, everything has healed, and so what determines your disability is your native resilience in the face of adversity, in the same way that what stops you from managing your diabetes appropriately is not access to healthcare or drugs or the way those drugs work but your approach to the management of the condition.”

The author makes the point that private health care faces a huge conflict of interest that does not serve patient needs, but also says:

“A therapy that is not lifesaving but aims to improve quality of life is easily sidelined if it is not championed. This is less of an issue in a society where healthcare is provided privately and is driven by the incentive for doctors to provide therapies in order to earn a living.”

What do you think are the advantages and disadvantages of private health care? Do you think your perspective would change if you had a somewhat rare medical need?

The author makes it clear that he finds treating older patients for pain especially rewarding because of their attitude, saying:

“I also find older patients more reflective about their pain and more understanding of the limitations of the science of suffering.”

Do you find that your attitude towards physical discomfort has changed as you’ve gotten older?

The author boldly claims that if you do not drink alcohol, exercise regularly, follow a good diet, and live mindfully in the moment “then it is likely you need never darken the door of a hospital or your GP” nor “trouble our psychologists.”

What did you think of this claim?

The author concludes the book by saying:

“My hope is that after reading this book you will take responsibility for your health and ask questions of those from whom you seek advice when you are unwell. That when you are in pain you will be able to reflect on the screaming of your primitive brain and understand that the experience of pain is a biological alarm, but your response is a choice. Hopefully you will understand that pain can never be completely extinguished with medicines and can appreciate their potential for harm.”

How did your experience of the book align with the author’s wishes?