Pain is something we’ve all experienced at one moment or another. Whether you stub your toe, burn your tongue, sprain an ankle, or live with arthritis, pain is a part of being human.

Acute pain (sudden and short term) is the body’s warning system, telling you the coffee is too hot, or the knife is too sharp. But when pain becomes chronic—typically lasting longer than three months—the warning signal malfunctions and can become the primary problem.

The CDC reports that chronic pain is one of the most common reasons adults seek medical care. And the pain itself isn’t the only problem. Chronic pain is linked to anxiety, depression, a reduced quality of life, and an increased risk of opioid addiction in the United States, not to mention other mental stresses that can lead to insomnia and chronic fatigue.

Approximately 50 million adults in the US report living with chronic pain. For women, adults living in poverty, and in rural areas the incidence is even higher. Getting older also increases the likelihood experiencing chronic pain.

Types of Pain

“Pain and our experience of pain are two different things,” explains Lillie Rosenthal, D.O., who works in private integrative pain practice in New York. Because pain can be multifactorial, the chronic pain we feel is sometimes amplified and shows up in areas of the body other than where it originates. Chronic pain has two broad categories:

  • Neuropathic pain comes from the physical damaging of the nerves themselves, typically caused by inflammation or infection.

  • Nociceptive pain doesn't cause nerve damage. Instead, it's generated from the body's reaction to a painful event such as a pulled muscle or broken bone.

When you injure yourself, nociceptors respond by sending a signal to the spinal cord. That signal travels to the brain via the spinothalamic tract, which acts as a relay system to the brain. It's basically a game of tag between neurotransmitters (aka chemical messengers).

Imagine a sprained ankle. Inflammatory cytokines released by immune cells activate nociceptors which respond by releasing a neurotransmitter. This neurotransmitter sends a message to the spine. A separate neurotransmitter receives this message and travels the spinothalamic tract to relay the pain message to the thalamus.

The thalamus sends a message to your brain communicating the location and type of pain. The process is part of the ascending pathway.

Because what goes up must come down there's also a descending pathway. The descending pathway is made up of neurons that regulate and inhibit the body’s response to the ascending pathway’s pain signaling.

The pain message travels to your brain via the ascending pathway and your brain responds via the descending pathway. During episodes of acute pain this system works to protect the body from further harm by activating a network of brain regions that affect somatosensory and emotional responses.

The Two Types of Nociceptive Pain

Breaking types of pain down a bit further:

  • Visceral pain originates in internal organs (the heart or intestines, for example). The pain is often reported as an “achy” feeling and can be difficult to pinpoint, because it comes from deep in the body. It can also be referred, meaning the pain is not experienced at the point of injury or damage. For example, we know that a heart attack can have symptoms including stomach, neck, teeth, or jaw pain.

  • Somatic pain comes from the skin, muscles, and/or soft tissues (aka the "outer body"). Arthritis or a joint injury such as a sprained ankle are two examples.

How Pain Becomes Chronic

To recap, when you sprain your ankle, your brain sends signals of pain that aim to prevent you from walking on the ankle and worsening the injury. Your brain may produce emotions of stress and fear that encourage you to rest and recover. During this type of acute injury, these signals are protective.

However, when this system malfunctions and the pain-signaling doesn’t “turn off,” your sensation of pain can become chronic.

Dr. Rosenthal explains that, “When acute pain is not comprehensively treated, there is a risk for developing chronic pain. We want to avoid this change, because pain chronification [the process of acute pain becoming chronic] leads to changes in our brains.”

There are different models and theories for exactly how pain chronification happens, but researchers can observe physical changes in the brains and neuroendocrine systems of chronic pain patients.

Beth Darnall, Ph.D., director of Stanford University's Pain Relief Innovations Lab, says, “This happens by directly amplifying pain processing in the central nervous system. If my attention is very focused on my pain, it will increase my pain experience. We can demonstrate and visualize this with a functional MRI."

Another related mechanism is amplification of negative emotions, Darnall explains: "If I feel fearful and very helpless about my pain, those emotions will similarly serve to amplify pain processing in the amygdala.”

The amygdala is part of the brain involved in experiencing emotions. When people have chronic pain, they may also experience the following:

  • Central sensitization: Localized or generalized pain generated solely in the central nervous system (CNS). Central pain is characterized by:

    • Hyperalgesia—an increased response to a painful stimulus

    • Allodynia—pain after a stimulus that is typically not pain inducing.

  • Fear avoidance

  • Pain catastrophizing, a pattern of negative cognitive-emotional responses to real or anticipated pain. Fearing and worrying about pain can essentially create more pain

  • Anxiety and depression

  • Insomnia or sleep disturbances

  • Chronic fatigue

The Role of Hormones in Chronic Pain

Hormones also play important roles in the communication, response, and potential chronification of pain. The body’s hypothalamic-pituitary-adrenocortical system (HPA) is what we refer to as the “flight or fight system.” The dysregulation and hyperactivity of this system can intensify the pain condition.

Robert Twillman, Ph.D., former executive director of the Academy of Integrative Pain Management (AIPM), explains, “When the human body is stressed, whether by physical activity, a physical injury, or something in the environment that is perceived to be threatening, the HPA axis is activated to help the body deal with that stress. The key step in the HPA axis’s activity is the release of adrenaline, noradrenaline, and cortisol from the adrenal glands.”

Regarding these hormones, adds Dr. Twillman, “Cortisol is especially interesting in the context of pain. It is an anti-inflammatory substance, so in the short term, it can be helpful in reducing inflammation and thus reducing pain."

However, when the HPA axis is activated for a prolonged period of time, the system essentially crashes, and cortisol production plunges, leaving the individual without its beneficial effects, he says explaining that, "Cortisol can also help consolidate memories, and in the case of pain, can create linkages among environmental stimuli, internal thoughts and emotions, and the experience of pain, such that some of those stimuli, thoughts, and emotions can later evoke the experience of pain.”

Recent advancement in understanding the role of hormones in chronic pain have led to the use of hormone therapy and the emerging practice of neurosteroids for pain management. During chronic pain hormones that are chronically elevated can become depleted and lead to a cascade of imbalances.

Some of these hormones work to protect nerve cells and regenerate them after damage. Neurosteroid therapy uses neurosteroids and can offer curative benefits, rather than simply reducing symptoms. This is because neurosteroids can effectively decrease the neuroinflammation that happens in response to damaged tissue.

The Mental Battle of Chronic Pain

Pain isn’t just all in your head, but your brain absolutely is a major player in pain sensation and recognition. Chronic pain is linked to many mental health concerns. For example, research suggests that between 30% and 50% of people who experience chronic pain also struggle with anxiety or depression.

It makes sense that constant pain would take a mental toll, but there’s more to clinical depression and anxiety that “feeling blue.” Science has found considerable overlap between pain-induced and depression-induced neuroplasticity changes and neurobiological changes in the brain. Meaning, both depression and pain share some of the same brain regions and can influence each other. Pain can influence mood and mood can influence pain.

The good news is that cognitive and behavioral therapy can help to reduce feelings of fear and depression that often accompany chronic pain. Darnall explains, “It’s natural to focus on pain and worry about it, but if this is a persistently strong pattern, it will worsen the pain experience."

Acknowledging pain is important, Darnall says: "It's also vital we gain a skillset to help calm the nervous system and steer ourselves toward behaviors that are self-soothing. This shifts attention away from pain and feeling helpless about it.”

Pain: Symptom or Stand-Alone Disease?

For years, practitioners have worked to better understand and more accurately classify chronic pain, resulting in the most recent update of the International Classification of Diseases (ICD), accepted by the World Health Organization (WHO) in 2019. The ICD-11 edition is the first one to include chronic pain as a “disease” and classifies six categories of chronic pain.

Chronic primary pain is defined as pain in one or more anatomic regions that persists or recurs longer than three months and is associated with significant emotional distress or significant functional disability that cannot be better explained by another chronic pain condition.

  1. Chronic cancer pain is pain caused by cancer and by cancer treatment.

  2. Chronic post-surgical or post-traumatic pain is pain that persists beyond the typical healing time. This type of pain is frequent after surgery and certain types of injuries and persists at least three months after surgery or tissue trauma. Chronic post-surgical pain is often neuropathic pain, which is usually more severe than nociceptive pain.

  3. Chronic neuropathic pain is caused by a lesion or disease of the somatosensory nervous system, which provides information about the body and includes skin, musculoskeletal, and visceral organs. Diagnosis of chronic neuropathic pain requires a history of a nervous system injury, such as stroke, nerve trauma, or diabetic neuropathy.

  4. Chronic headache and orofacial pain include both primary (idiopathic) and secondary (symptomatic) pain and is defined as occurring 50% of days for at least three months.

  5. Chronic visceral pain is persistent or recurring pain that originates from internal organs of the head and neck, or the thoracic, abdominal, and pelvic cavities.

  6. Chronic musculoskeletal pain is persistent or recurrent pain that comes from a disease that directly affects the bones, joints, muscles, or related soft tissues (tendons and ligaments). Chronic musculoskeletal pain is limited to nociceptive pain and characterized by persistent inflammation—usually from autoimmune or metabolic causes, such as rheumatoid arthritis.

The official classification of pain as a disease by the WHO is a distinctive and historical decision because how an ailment is classified often dictates how it is treated.

For instance, if pain is defined as a symptom of an underlying condition, such as from arthritis, a doctor’s approach will be to treat the arthritis, and ideally, the pain will be relieved as well as part of the treatment course. However, when chronic pain is considered a disease itself, incorporating multiple related symptoms and mental health aspects, pain management takes on a more integrative approach.

Think back to pain chronification—when chronic pain develops as part of a chronic condition or in connection with multiple conditions, such as fibromyalgia, CRPS, and migraine, it is often the result of a dysregulation of the body’s pain signaling system.

“Chronic pain tends to be life-limiting because we may erroneously interpret it to be telling us to lie on the couch all the time, as we become more withdrawn, depressed, weak, and frail," says Twillman. "To me, that is what makes chronic pain a disease—like any disease, it is life-limiting.”

Think of your body like an orchestra—an intricate performance of different systems working in harmony. When there is an injury, the neurological, hormonal, and biological systems function separately. When any of these systems (or the communication between these systems) becomes dysregulated, the experience of pain can exist separately from the initial pain sensation. Our daily activities, practiced behaviors, psychology, social relations, and lifestyles can all influence these systems.

This interplay between what we do, think, feel, and the physical changes in our bodies and pain experiences, have led many practitioners to focus on a biopsychosocial approach to pain management.

A New Approach to Pain Management

Understanding the type and origin of pain is an important part of treatment. The biopsychosocial approach to pain management—which has emerged as the optimal way to treat chronic pain in recent years—views chronic pain as an interaction among various biological, psychological, and social components and uses an integrative approach to manage the pain condition.

Biological components consider a person’s hormones, genetics, and natural pain modulating compounds and works to increase processes that soothe pain sensations.

Psychological includes various types of therapies. The type of therapy should be tailored for your needs and may include:

  • Talk therapy

  • Behavioral therapy

  • Group therapy

  • Pain management classes

  • Exercise—both aerobic and resistance training—has been shown to be beneficial and can be used to regain functional capacity and to reduce feelings of anxiety, depression, and pain catastrophizing.

Social focuses on cultural and societal influences, support networks, socioeconomic factors, and personal relationships. The goal of social intervention is to create the optimal environment for a person to achieve improved health, with understanding and acknowledgement of their unique circumstances.

Nutrition acknowledges the key role of food and drink on health and wellbeing—including mental health.

Using the biopsychosocial model, therapeutic interventions may be combined to offer patients a multifaceted treatment plan with multiple clinicians involved.

“If we alter our thoughts that movement is going to be painful and result in further injury, we may find that we can change our behavior by becoming more active while simultaneously reducing our emotional experience of anxiety and depression," says Twillman. "We also have to recognize that thoughts, emotions, and behaviors are inextricably bound to biological processes. Psychological factors change biological processes and vice versa.”

The biopsychosocial model works best with a team of doctors (primary care or pain specialists monitoring your pain and your meds or procedures, a disease-specific specialist such as a rheumatologist if you have an arthritic condition for example, a physical therapist, and a psychologist or therapist. A clinical pharmacist is also a good addition to be sure there are no contraindications or risks with your various meds.

The biopsychosocial model works by positively influencing our nervous system, as well as our hormonal signaling and immunological functions. Behavioral medicine strategies work by dampening the “harm alarm.”

FMRI and MRI research shows that negative cognitive patterns predict increased pain processing and over time can create brain changes that correspond with increases in pain sensations. Altering these negative patterns (such as pain rumination, focus on pain, and feelings of helplessness) can alter brain function and correspond with decreased pain sensations.

Lack of social support, financial distress, and insecurity are examples of social factors that can augment the release of stress hormones and send signals to the brain that exacerbate pain signaling.

Physical inactivity can increase pain due to losses in flexibility, muscle mass, and positive hormonal responses to exercise. Pain can induce a fear of movement as the person seeks to guard their body, which further decreases movement and increases pain sensations. Physical therapy can help a person to be more active, and consequently decrease brain signaling that induces feelings of fear and alerts to “protect the injury."

Diet plays an important role in pain modulation, mainly due to its effect on the gut microbiome—micro-organisms that live in our gastrointestinal tract and work to synthesize hormones and vitamins, break down nutrients, and build resistance to disease-causing pathogens.

Finally, your gut and brain are in constant conversation. Inflammation of the gut and imbalance in bacteria (gut dysbiosis) can trigger an inflammatory immune response, increase alarm messaging to the brain, and worsen feelings of anxiety and depression by influencing regions of the brain that help to regulate emotions. So nutrition is also an important aspect of care.

Chronic pain can affect every aspect of your life. Fortunately, behavioral intervention can influence the pain experience and induce changes in your brain, hormonal expression, and immune response. Finding knowledgeable clinicians and a reliable support team is often an essential part of pan management.

Darnall reminds us, “The mechanisms by which acute pain becomes chronic is multifactorial. It can include the immune system, gut microbiota, stress hormones, cognitive and emotional factors, engagement in rehabilitation (or not), pain history and pain-specific responses, sleep quality, and even the types of medications we are taking."

Behavioral medicine focuses on helping people understand which actions will help steer neurobiology towards relief in the moment and improved management of pain in the long run (ideally, healing and extinguishing pain).

What an Integrated Pain Care Model Feels Like

Your care team and the tools used are dependent on your individual pain experience, although some general techniques have been effective in recent studies. For example, changing a patient’s focus away from negative emotions and catastrophizing.

In a pilot study, Darnall and colleagues used a single session to teach pain patients cognitive behavior techniques to limit pain catastrophizing. Preliminary results showed that a single educative session of behavioral therapy could function as an effective treatment.

What we eat, how we move, our social and familial relations, and perception have all been shown to affect the experience and processing of pain. New understandings, new definitions, and new models of pain management offer advancement in the understanding and treatment of chronic pain.

It is important to remember that the physiological and emotional components of pain do not minimize or lessen its impact and importance. Behaviors and thoughts can alter physical, brain, and chemical responses. If you are experiencing chronic pain, it is important to discuss your treatment options with trained and knowledgeable professionals and to reach out for support—you are not alone in your chronic pain journey.

Like any chronic condition, pain can be scary. Even if there is no cure, understanding and confronting your pain with knowledge and compassion can improve your health, wellbeing, and daily living.

This article was originally published May 18, 2021 and most recently updated May 24, 2021.
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