The Landscape of Chronic Pain

The Landscape of Chronic Pain: Broader Perspectives – free full-text /PMC6572619/ – by Mark I. Johnson – May 2019

Here is a recent lengthy review of what’s known about chronic pain: the various aspects of various types of pain under various circumstances.

This article shows the folly of making any numerical one-dimensional measurement of chronic pain, which can arise from a variety of causes, vary greatly over time and location, and make such intrusive incursions into our inner lives.

This special issue on matters related to chronic pain aims to draw on research and scholarly discourse from an eclectic mix of areas and perspectives.  

The purpose of this non-systematic topical review is to précis an assortment of contemporary topics related to chronic pain and its management to nurture debate about research, practice and health care policy.

The review discusses the phenomenon of pain, the struggle that patients have trying to legitimize their pain to others, the utility of the acute–chronic dichotomy, and the burden of chronic pain on society.

The review describes the introduction of chronic primary pain in the World Health Organization’s International Classification of Disease, 11th Revision and discusses the importance of biopsychosocial approaches to manage pain, the consequences of overprescribing and shifts in service delivery in primary care settings.

The second half of the review explores pain perception as a multisensory perceptual inference discussing how contexts, predictions and expectations contribute to the malleability of somatosensations including pain, and how this knowledge can inform the development of therapies and strategies to alleviate pain.

Finally, the review explores chronic pain through an evolutionary lens by comparing modern urban lifestyles with genetic heritage that encodes physiology adapted to live in the Paleolithic era. I speculate that modern urban lifestyles may be painogenic in nature, worsening chronic pain in individuals and burdening society at the population level.

1. Introduction

The purpose of this topical review is to précis an assortment of contemporary issues related to chronic pain and its management to reveal the landscape of current knowledge and thinking in the field

2. The Paradox of Pain

“To live in pain is not only to suffer aversive sensations but to be caught in a web of paradoxes”
Leder [4],

2.1. Defining Pain

Historically, clinicians viewed pain as a secondary symptom of injury and disease and focused treatment on removing the precipitating (primary) cause.

Nowadays the importance of alleviating pain is widely accepted. The International Association for the Study of Pain (IASP) defines pain as:

‘An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.’

This is because pain is a psychological state produced by the brain in response to a multitude of biopsychosocial inputs of which activity in nociceptive (noxious detecting) pathways is but one.

…management of chronic pain remains a challenge and the burden of chronic pain on society continues to rise. Pain is complex.

2.2. The Lived Experience of Pain

The lived experience of pain is a perplexing mix of sensory, emotional and cognitive phenomenon that fluctuate in and out of conscious awareness.

The unpleasant nature of pain demands attention, explanation and action to resolve actual or potential damage of the body.

An assortment of biopsychosocial and environmental factors influence the appearance, severity, character, and time course of pain, although often pain is unpredictable.

Pain may occur in response to noxious stimuli, innocuous stimuli or in the absence of any apparent stimuli.

From a phenomenological perspective people report their experience of pain

• to fluctuate in the present and the past and the future;
• to be localized and radiating everywhere;
• to be productive and destructive of value and meaning; and
• to be never changing and ever-changing [4].

Often pain is amorphous.

2.3. Why Do We Communicate Pain?

Expression of pain is at the core of human group dynamics, serving to inform other individuals that you are injured or ill. In modern society expressing pain has the potential to generate empathy in others to motivate them to offer aid.

Individuals evaluate a person’s expression of pain to determine the extent of their disability and whether the person can fulfill their responsibilities

It seems plausible that evolution has hardwired the nervous system to exaggerate expression of pain (to be believed) and paradoxically hardwired the nervous system to be skeptical about the existence of pain in others (to prevent being duped).

This paradox plays out in the adversary struggle that chronic pain patients experience when trying to legitimise their pain in the health care system.

3. The Struggle to Legitimize Pain

“To have pain is to have certainty;
to hear about pain is to have doubt”
-Scarry

Truer words were never spoken.

3.1. Disproving Pain

Communicating the complex, dynamic, and multidimensional nature of pain experience is a challenge.

The amorphous character of pain does not sit comfortably with the objective nature of medical practice and evidence suggests that chronic pain patients have difficulties convincing health care professionals of the existence of pain

Pain is a perceptual experience that is personal to the individual and by definition unobservable by another person. The subjective nature of pain makes it is impossible to prove or disprove a person’s pain and therefore it is not possible to distinguish a person’s report of pain experience from that of tissue damage.

A person’s report of pain should be accepted if their sensory and emotional experience of pain is expressed in the same ways as that caused by tissue damage. This was recognised in 1968 by McCaffery who defined pain as

‘…whatever the experiencing person says it is, existing whenever the experiencing person says it does’

…conveying pain experience depends on an ability to use language and/or behavioral action to communicate the internal state of one’s body. It also depends on an ability to persuade others of the existence of pain in oneself.

Likewise, the observer needs to be receptive to what is being communicated, including being able to interpret the meaning and importance of both verbal and behavioral information.

3.2. The Tenuous Link between Pain and Pathology

Skepticism about the legitimacy of another person’s pain is at its height when there is an absence of evidence of injury or disease.

Subjective and objective assessment, including the patient’s report of symptoms, examinations of functional capacity, and diagnostic tests, contribute to pain diagnoses.

When legitimizing pain and constructing logical explanations for pain, patients and non-pain specialist practitioners tend to give credence to positive diagnostic tests related to tissue pathology, at the expense of alterations in physiological processing associated with pain se (e.g., central sensitisation).

• Pain may occur in the absence of injury.
• Pain may occur in the presence of minor injuries.
• Paradoxically, serious injuries may be devoid of pain.
• Pathology may not always be driving pain.

3.3. Pain is Not a Unitary Phenomenon

Clearly, the dynamic, multidimensional, and amorphous nature of pain is challenging to capture with any degree of specificity and precision.

Commonly, pain is reduced to a unitary phenomenon measured by numerical intensity rating scales. This approach is convenient and psychometric research evidence suggests that data gathered from scales is valid and reliable

However, rating scales do not measure pain objectively and can give a false impression of the level of measurement precision (e.g., 1 mm on 100-mm visual analogue scale).

Scales presume linearity of subjective report between scale ends and use anchors that are nebulous (e.g., ‘The worst-ever pain’ or ‘The worst pain imaginable’).

The measurement of pain in this way is not only imprecise but is also fails to capture the complex and subjective nature of pain.

Wideman et al. have offered a multimodal assessment model of pain that describes quantitative aspects of pain such as self-reported and non-self-reported measures, and importantly, qualitative aspects of pain such as the words and behaviors of the patient’s narrative.

The inclusion of, and importance paid to, the narrative report captures more fully an individual’s pain experience helping to legitimize pain for both patient and practitioner.

4. Chronic Pain

4.1. Reassessing the Acute–Chronic Dichotomy?

Traditionally, service delivery and clinical practice views pain through an acute or chronic lens.

1. Acute pain is pain persisting less than twelve weeks.
2. Chronic pain is often secondary to disease or traumatic injury and initially considered a symptom.

Recently, Loser argued that the acute–chronic dichotomy is so entrenched in pain parlance that it has escaped critical scrutiny.

There are no temporal correlates of physiological processes associated with pain based on time points used to distinguish acute and chronic.

Loser argues that we should describe pain syndromes based on physiological mechanisms, including peripheral or centrally generated perspectives as originally discussed by John Bonica in the 1950s.

From an evolutionary perspective, hypersensitivity of the nervous system serves to assist the healing process by amplifying and prolonging pain. This discourages use of, and contact with, injured tissue.

Peripheral sensitization is driven by the release and production of biochemical mediators at the site of tissue damage that lower the threshold of activation of transducer ion channel receptors expressed in nociceptor terminals

Central sensitization is centrally mediated amplification of pain irrespective of mechanism or location. Central sensitization is triggered by noxious (excitatory) input arising from direct activation of nociceptors (nociceptive) or from damaged or dysfunctional neuronal fibers (neuropathic).

The receptive fields of central nociceptive transmission neurons also expand so that they become responsive to stimuli applied to areas of tissue that do not normally activate them. Thus, central sensitization increases the area of pain hypersensitivity across body parts.

Central sensitization manifests primary and secondary hyperalgesia and allodynia and sometimes pain presents spontaneously in the absence of nociceptive stimuli.

Here, he uses the term “hyperalgesia” as meaning extreme pain sensitivity, completely unrelated to the urban myth of “opioid-induced hyperalgesia”.

Patients may present with widespread pain in multiple body regions and pain arising after mundane activities such as walking or cooking.

4.2. Nociplastic Pain: A New Mechanistic Descriptor?

Presently, mechanistic categories of pain are;

1. nociceptive pain, resulting from activation of nociceptors by a noxious stimulus that is damaging or threatens damage to healthy tissues (other than neural structures); and
2. neuropathic pain resulting from a lesion or disease of the somatosensory nervous system.

Recently, Kosek et al. have proposed consideration of a third mechanistic descriptor, nociplastic pain to describe pain arising from altered central nociceptive processing in the absence of tissue damage

It is important to recognize that the terms nociplastic, nociceptive and neuropathic are not diagnoses or exclusive categorical labels but descriptors of concurrent potential mechanistic drivers of pain.

4.3. The Burden of Chronic Pain

Most literature discusses pain from an acute–chronic dichotomy.

People do not die directly of pain, and unlike functional impairment, pain is not visible.

Pain is often secondary to other medical conditions. Health care policies often focus on curing or slowing progression of the primary disease as a means to improve functional outcome, and may neglect pain management.

For example, pain is underdiagnosed and inadequately managed in neurological conditions despite high prevalence.

• Parkinson’s disease
• multiple sclerosis
• and Alzheimer’s disease

4.4. International Classification of Diseases: Chronic Primary Pain

The 11th edition of the World Health Organization’s International Classification of Diseases (ICD-11) categorises chronic pain as secondary to other conditions:

• chronic cancer-related pain,
• chronic neuropathic pain,
• chronic secondary visceral pain,
• chronic posttraumatic and postsurgical pain,
• chronic secondary headache and orofacial pain, and
• chronic secondary musculoskeletal pain

ICD-11 includes a category for chronic primary pain to reflect in part that pain should be regarded as a pathologic entity in its own right and characterized by a dysfunctional nervous system with persistent central sensitization

Chronic primary pain defies classical pathological based classification.

Specific examples include

• chronic widespread pain,
• fibromyalgia,
• irritable bowel syndrome and
• non-specific chronic low back pain

5. Desirable Models of Care

It is recommended that patients with chronic pain are managed using a biopsychosocial model of care with pharmacological and non-pharmacological interventions tailored to the needs of the individual.

As with all medical care, any intervention MUST be tailored to the individual,

1. their internal biochemical environment,
2. their internal psychological state, and
3. their external environment (including what foods are consumed).

The need of this particular individual (me) is

1. opioid medication to treat my internal biochemical environment (chronic acute pains from EDS),
2. my psychological state is constant low-level anxiety with periodic flares of disabling dread (due to biological complications of EDS), and
3. my external environment is clean and quiet and I eat mainly non-processed food. 

5.1. The Analgesic Ladder

The World Health Organization’s analgesic ladder, initially developed for cancer pain [45], advocates a stepwise approach to prescribing starting with mild analgesics and increasing dosage or switching to powerful analgesics if pain is not adequately managed.

This is what any decent doctor would do. 

I and many other patients I’ve corresponded with went through a long drawn-out process of many trials of non-opioid pain management and only when they all failed were we prescribed opioids.

Analgesic drugs interact with nociceptive pathways to inhibit the onward transmission of noxious information from the site of injury to the brain in order to alleviate pain

• Non-steroidal anti-inflammatory drugs inhibit cyclooxygenase reducing the production of prostaglandins that normally sensitize nociceptors;
• opioids prevent onward transmission of nociceptive transmission in the central nervous system; and
• local anesthetics block sodium channels reducing transmission of nerve impulses in nociceptive fibers.

5.2. Overprescribing

Abuse of prescription opioids is a major problem in some Western countries, although paradoxically, restricted access to opioids impedes pain management in parts of Asia, Africa, and Middle East.

Abuse of prescription opioids demonstrates the need for greater caution and selectivity in prescribing of long-term opioid therapy. Ironically, as one drug loses favor others come into view.

I assume they are talking about abused drugs because the popularity of street drugs follows this pattern. When one drug is restricted, people with addiction merely move on to the next, while patients with a legitimate need for opioids have no such choices.

5.3. Novel Centrally Acting Drugs

There is low-level evidence that cannabinoids alleviate neuropathic pain and insufficient evidence to recommend their clinical use for other types of pain

Presently, professional bodies recommend that cannabinoids be considered in exceptional circumstances for neuropathic pain, chronic non-malignant pain and cancer pain when patients are not responding to other treatment.

I sure wish this worked for me because I’m in a state where marijuana is legal.

Centrally acting psychedelic drugs such as lysergic acid diethylamide and psilocybin have also attracted interest for the management of chronic pain.

I believe such a drug could be extremely helpful in shifting my mental state, which has been hammered down by pain for decades, from a defeated mindset to a more positive mindset focusing on possibilities.

Psychedelics act as agonists at 5-HT2A receptors and may modulate pain through action in the rostral ventromedial medulla enhancing descending pain inhibitory pathway activity

Psychedelics influence metacognitive interpretation of pain including the resting state of awareness mediated by the default mode network in the brain

It’s exactly this “awareness” and “interpretation” of my pain that I would hope to change with psychedelics – if I could find such drugs in my law-abiding lifestyle.

6. Service Delivery in Primary Care

The value of analgesic medication is undisputed providing it is within a biopsychosocial model of care.

The anti-opioid zealots are insisting this is not the case, that opioids “don’t work” for chronic pain.

How would they know if they haven’t tried opioids for their own chronic pain?

How can THEY decide if our medication is alleviating our pain or not?

A comprehensive approach to assessment is optimal to address physical, emotional, and social functioning and a palliative approach is optimal to manage pain and distressing symptoms because there are no curative treatments.

7. Pain Perception: Active Top-Down Processing?

Classically, a ‘bottom-up’ stimulus-organism-response modeldescribes the physiological processes involved in producing pain sensation.

The model inadvertently implies that pain is an inevitable consequence of activity in the nociceptive system driven by tissue damage.

Melzack suggested that the multidimensional experience of pain resulted from

• characteristic patterns of nerve impulses (i.e., a neurosignature)
• produced within multiple widely distributed neural networks in the brain that
• are genetically determined and modified by sensory experience (i.e., body-self neuromatrix theory of pain).

This makes sense to me as the physical response to “amorphous pain”,

• which cannot be precisely located,
• that resists categorization or definition,
• that varies from moment to moment

7.1. Maleability of Perceived Properties of the Body

Predictions and expectations are a core feature of the central nervous system processing enabling the brain to generate perceptual experiences based on snippets of multisensory input.

This ‘perceptual inference’ is involved in the generation of the sense of ownership of body parts, and in the location of sensory events, including pain, within the body. The perceptual qualities associated with the sense of body ownership are malleable as demonstrated by somatosensory illusions.

7.2. Multisensory Perceptual Inference as a Protector

Pain is never motivationally neutral.

Pain is a potent driver of action in much the same way as thirst drives drinking and hunger drives eating, because the cost of ignoring pain may result in tissue damage, disrupted homeostasis and threat to life.

Outcomes of behaviors that do not meet predictions (i.e., are unexpected with a large prediction error) have a major influence on future behavior.

Unexpected pain, such as a severe lancinating shooting pain during an innocuous movement, is likely to have a disproportionately large effect on the expected intensity of future encounters with the same stimuli.

Unexpected pain is likely to amplify multisensory perceptual inference serving to protect the integrity of tissue by creating, for example, fear-avoidance of movement (i.e., the motivational-decision model of pain,

I feel this is part of my struggle with the various pains in various places: I cannot predict

• what action will be painful
• where in my body
• under what circumstances.

I regularly pour myself coffee in the morning without a second thought, yet… every now and then, I lift the carafe and a sudden sharp spike of pain attacks my wrist. Luckily, it fades quickly, but afterward, I use the other hand to avoid it.

Sometimes I’ll just be walking down a hallway when an intense sharp pain shoots into one hip, so unexpected that I almost stumble from the shock of it. But again, it fades quickly so I proceed walking after catching myself.

Some days I’ll spend a few hours with a friend watching TV and, in the middle of the following night, wake with a piercing headache that lasts for days because I didn’t hold the correct posture while watching. I’m still not sure exactly what posture brings on the headaches and it doesn’t happen all the time.

And these sharp nociceptive pains occur in addition to the more generalized constant dull aching pain in and around my low back, sacroiliac joint, hips, and thighs where I have the worst problems.

Contemporary models of pain perception are attempting to integrate sensory, affective, cognitive, social, and bodily cues interpreted within social, environmental and evolutionary contexts, including previous experiences, from the perspective of embodied cognition.

7.3. The Theory of Embodied Pain

The embodied theory describes pain as a dynamic, motor experience rather than a passive, sensory experience and blurs the distinction between perception and action:

“Pain is always about action.”

…the brain uses information about previous encounters with pain and previous behaviors on pain to ‘flavour’ pain experience.

7.4. Multisensory Perceptual Inference to Alleviate Pain

Therapeutic opportunities can arise from manipulating the environment and context to reinstate coherence of behavior and normalize perception.

This section delves into virtual reality as a means of reducing pain perception. I’m not convinced it can help my serious pain.

8. Social and Environmental Contexts

8.1. Lifestyle and Chronic Pain

Modern urban lifestyles are associated with mortality and morbidity of noncommunicable ‘lifestyle’ diseases, such as cardiovascular diseases (heart attacks and stroke), chronic respiratory diseases (chronic obstructed pulmonary disease and asthma), diabetes and cancer

Chronic pain is a secondary consequence of many of these non-communicable diseases causing suffering, disability and a significant impact on quality of life.

Yet, none of this applies to me:

I’m still in excellent condition, probably from my previous pursuit of competitive activities and healthy eating. I take care to maintain my body to maximize my functionality, which is increasingly limited by pain. Still…

• I exercise by at least walking daily,
• I eat almost exclusively “simple” food (the least processed), and
• I get enough good sleep.

So they cannot claim my pain comes from “unhealthy lifestyle”.

Built and food environments are known to promote obesity in populations and has been described as obesogencity of urban environments

8.2. Painogenicity of Modern Urban Living

Painogenicity is the sum of influences that the surroundings, opportunities or conditions of life have on promoting persistent pain in individuals or populations

Modern urban environments generally consist of

• air polluted with toxic emissions and particulates,
• high population densities, 
• limited green open space and
• readily available processed foodstuffs.

None of these factors apply to me because I live in a small neighborhood in a remote area surrounded by CA State Parks.

8.3. Chronic Pain and Evolutionary Mismatch

Evolutionary mismatch may provide insights to potential painogencity of modern urban environments.

Our genetic heritage encodes physiology adapted for hominin ancestors that existed in the Paleolithic era, circa 4–7 million years ago with clean air, exposure to microorganisms and lifestyles consisting of walking, climbing, lifting, carrying and bending and diets of fresh vegetables, fruit and raw meat (i.e., hunter-gatherer lifestyles).

In contrast, modern urban dwellers exist in towns and cities and have lifestyles that are indoors and involve consumption of over-processed foods, and prescription and recreational drugs.

Modern urban lifestyles are becoming increasingly sedentary with excessive amounts of time being physically inactive leading to ‘disuse syndromes’ (e.g., ‘walking deficiency syndrome’, ‘hyper-sitting syndrome’) and an increased risk of non-specific chronic musculoskeletal pain

Current models of care for chronic pain, especially related to the musculoskeletal system, promote lifestyle adjustment. In essence, they are attempting to rebalance this evolutionary mismatch. Physical activity and diet is at the core of lifestyle adjustment (e.g., for non-specific chronic low back pain).

Been there, done that, and yet my pain persists.

9. Upstream for Solutions

Clinical guidelines recommend that practitioners counsel people living with persistent pain to undertake healthy lifestyles

ain education about the nature of lifestyle adjustments is prominent in pain discourse but incongruous social and environmental conditions may hinder long-term behaviour change.

10. Conclusion

I have argued that pain is perplexing, subjective and amorphous and some patients feel that health care providers do not believe that they have significant pain.

I have argued that it is not possible to disprove a person’s pain and that the association between pain and pathology may be tenuous in some circumstances.

Ultimately, pain is a psychological construct arising from physiological processes occurring in the brain.

I have described pain as a top-down perceptual inference that integrates sensory, motor, affective, cognitive, social and environmental contexts to update the final experience of pain.

I argue that pain does not faithfully reflect tissue status but serves instead to infer bodily threat and drive behaviors to reduce the impact of threat on the integrity of the body.

Finally, I have speculated that modern urban environments are painogenic in nature and incompatible with Paleolithic physiology encoded by our genetic heritage.