Developments in Psychological Therapies for the Treatment of Chronic Pain

What is pain? Is it physical or psychological? Why do we experience pain? These are some of the common questions that scientists and clinicians ask themselves to be better able to assist patients dealing with chronic pain. 

Pain is a signal in your nervous system that tells your body that something is wrong [1]. The external feeling of pain can differ depending on many factors, but it will usually be some type of prick, tingle, sting, burn, or ache [1]. It is true that not all pain is the same. Generally, it is categorized into two types–chronic and acute pain. 

Chronic pain is defined as pain that lasts for longer than three months and occurs in a specific location in the body [2]. It can be divided into two categories: nociceptive, which is caused by tissue damage, or neuropathic, which is caused by damage to the peripheral or central nervous system [2]. The central nervous system (CNS) is composed of the brain and spinal cord while the peripheral nervous system is composed of the nerves that extend throughout the body.  Arthritis, an inflammatory joint disease, is one such example of nociceptive pain since it involves the destruction of tissues; multiple sclerosis, a chronic illness affecting the brain, is an example of neuropathic pain since it affects the brain, spinal cord, and optic nerves [3]. In comparison, acute pain is pain that occurs immediately after the pain response is received, and is typically very severe. If acute pain lasts longer than a given recovery period, it may become chronic pain [4]. This will usually occur if the injury or trauma that caused acute pain is not treated properly [4].  

When chronic pain occurs, there is an obvious physical burden on an individual, and their day-to-day life is immensely impacted in a variety of ways. However, chronic pain is not simply a physical burden–chronic pain conditions have been found to be in the top 10 leading causes of disability across the world [5].Thus, most, if not all, chronic pain conditions are a contributing factor to unemployment rates [6]. Additionally, different pain and research groups evaluated the risk for suicide in those with different chronic pain disorders, and it was found that they were at a higher risk [7]. Specifically, pain-related depression and migraines were at the highest risk for a suicide attempt [7]. Overall, chronic pain has an impact on many aspects of an individual's life and well-being. Despite the dire need to find solutions for chronic pain, pain research only receives approximately 1-2% of the NIH funding [8]. 

In general, the treatment of chronic pain has been a matter of controversy in many research and clinical settings for years. Because of the complicated neurological pathways behind pain, many treatments, such as opioids, are ineffective and result in addiction. Recently, however, chronic pain has begun to be addressed through psychotherapies, drugs outside of opioids, and virtual reality technology.

Neuroscience Behind Chronic Pain

The neuroscience of pain is extremely complicated. Thus, it would be impossible to explain every aspect of it. However, this article will explain the key aspects of chronic pain and how it results from acute pain. 

When a painful stimulus comes into contact with the skin, a nociceptor (sensory) fiber detects it and sends the information to the brain [9]. Then, receptors receive these signals in the dorsal horn, an area of the spinal cord also known as the processing center. The dorsal horn is composed of excitatory and inhibitory neurons as well as projection neurons, neurons that extend to more distant parts of the CNS. The brainstem receives the pain stimulus signal and transmits it as sensory information to other areas of the brain [10]. This pathway from physical stimulus to a chemical signal is facilitated by neurotransmitters, which are chemical messengers that transmit information across a chemical synapse, or gap between neurons, from one neuron to another neuron, muscle, or gland cell [9]. Neurotransmitters can be either excitatory, facilitating transmission of messages, or inhibitory, hindering the transmission of messages. Excitatory neurotransmitters are important for processes that require brain and body activity [9]. Inhibitory neurotransmitters both induce sleep and filter out unnecessary excitatory neurotransmitters [9]. Both of these types of neurotransmitters are essential for the modulation of pain. Specifically, if excitatory neurotransmitters act without an inhibitory neurotransmitter, pain results [9]. 

Furthermore, the two main pathways involved in the nociceptive messages to the brain are the spinothalamic and spinoreticular tracts [9]. A tract is a bundle of nerves in the CNS that act to transmit one particular network of signals. The spinothalamic pathway is involved in localizing pain, whereas the spinoreticular pathway is involved in the emotional aspects of pain [9]. There are certain specific regions within the brain that are activated during a painful experience such as the somatosensory cortex, a part of the brain that both receives and processes sensory information [9,11]. 

Persistent pain sensation that is associated with the transition from acute to chronic pain involves the modulation by specific types of cells known as glial cells, specifically astrocytes and microglia [12]. These are the support cells of the central and peripheral nervous systems that together regulate and maintain the intraneuronal space, by clearing up and recycling cellular material such as neurotransmitters [13]. Astrocytes are involved in neuronal signaling and controlling the amount of neurotransmitters surrounding the synapses. Astrocytes also form the blood-brain barrier, which only allows in the substances that are meant to be in the brain, and recycles left-over neurotransmitters [13]. In comparison, microglial cells respond to injuries and diseases in the central nervous system [13]. Both microglial cells and astrocytes mediate neuronal excitability, and an increase in these cells may lead to increased release of neurotransmitters and nociceptive activity [12]. 

Although the types of signaling involved in all types of pain are essentially the same, chronic pain is characterized by what scientists call “central sensitization” where the nervous system becomes highly sensitive to pain and sensations [14]. At the molecular level, central sensitization occurs as a result of prolonged nociceptive pain that causes the pain signal to be more likely to be transmitted [12, 15]. Additionally, the field of response, or the receptive field, is wider, causing the patient to experience pain even if the pain is not there [15]. Besides this, the threshold that the signal needs to reach is lowered, causing the pain to essentially be an “illusion” molecularly [15]. 

Patients experiencing central sensitization may also be hyper aware of their injury. As a result of hyper awareness of their pain, there may be alterations in an individuals neuronal connectivity as well as brain structure, function, and chemistry [8]. One region of the brain that is notably impacted by chronic pain is the dorsolateral prefrontal lobe. The dorsolateral prefrontal lobe is involved in higher-order thinking as well as working memory, which guides decision making [8]. 

Additionally, due to chronic pain over time, there is a loss or decrease in gray matter in this brain region [8]. Specifically it has been found that there is a loss of gray matter in the amygdala and the hippocampus [16]. The amygdala is involved in emotional response while the hippocampus is involved in emotion and consolidation of memories [16]. Given the involvement of both of these structures, changes in emotional and cognitive functioning may result. Thus, these changes in gray matter and the chemistry of the brain may overall impact the connections made between structures and regions of the brain [8]. Besides changes in brain structure, there may be a decrease in monoamine neurotransmitters such as serotonin, dopamine, and norepinephrine, which are all involved in depression [16].

The History of Opioids For Pain Treatment 

While the use of opioids to treat chronic pain has recently in the last 20 years become more common, there is evidence for their uses for other purposes thousands of years prior. At first, opium may have been used for ritualistic purposes, but by 1500 B.C., its use was more directed towards medical and pain relieving purposes [17]. During the 1600s, chronic pain was thought to have resulted from aging [18]. The next evolution in the use of opioids to treat pain followed in the 1800s with the use of morphine [17]. Following the invention of the hypodermic syringe, it began to be used for surgical purposes [17].

By the 1900s, the use of opioids was widespread and regulation was lacking. Cocaine and opioids were widely prescribed for a variety of everyday ailments ranging from diarrhea to a headache [12]. In 1995, the American Pain Society released their campaign for “pain as the fifth vital sign” which served the purpose of encouraging researchers to find an effective treatment for pain [18]. Alongside this, in the year 2000, The Joint Commission (TJC) published standards for treating pain in the clinical setting that emphasized the need to treat pain efficiently and effectively [18]. Due to both the American Pain Society’s campaign and the standards published by TJC, it was found that hospitals that treated pain, especially with opioids, received higher satisfaction [18]. 

In 1996, Purdue Pharma produced and aggressively marketed the drug OxyContin as an option for the treatment of chronic pain. Their main target was physicians who already prescribed a high-level of opioids for their patients. Although OxyContin and other opioids were shown to be an effective treatment for acute pain, there was a lack of evidence for its effectiveness and long-term effects for the treatment of chronic pain [19]. By citing sources that addressed addiction from acute pain, such as severe burns, Purdue Pharma was able to spread a misleading message that risk of addiction was less than one percent [19]. However, by 2004, OxyContin was the main drug of abuse in the United States [19].

Pharmacological Treatments for Chronic Pain

A misconception that some people may have about various types of addiction is that if the addictive substance is harmful to the individual, they should be able to easily stop using it once they realize the problem. It is unfortunately not that easy. Opioids are scientifically defined as a compound that attaches to an opiate receptor [2]. When an opiate goes through the bloodstream to the brain, it attaches to mu opioid receptor. These specialized receptors, when bound with a chemical, initiate biochemical reactions that cause feelings of pleasure that result from engaging in things like eating or sex [20]. In the absence of severe pain, the use of opioids may become addictive as its sole purpose becomes to initiate feelings of pleasure. Additionally, during withdrawal from chronic pain, patients tend to have difficulties in distinguishing between their symptoms of chronic pain and symptoms of withdrawal [2].  

An issue with treating chronic pain with opioids is the tolerance that results from its long-term use. As a person continuously uses opioids, they gain tolerance, which occurs as the receptors become less responsive to the binding of the opioid over continued use [20]. Because of this, the person may be advised by the physician to increase the dosage of the opioid in order to alleviate their pain [2]. Sometimes, the patient themselves may increase the dosage as a result of their own decision-making. However, increasing doses over time cause opioid dependence that eventually leads to addiction [20]. Prolonged use of opioids causes changes in the brain's circuitry. Thus, if an individual attempts to stop using the drug, they may experience severe symptoms of withdrawal since their brain essentially incorporates it into their day-to-day system. 

Given the complexity within the neurophysiology of pain, treatments are often extremely varied. Oftentimes, the treatment of choice has been pharmaceuticals [21]. Typical agents used include gabapentin and pregabalin, which both decrease the release of glutamate, an excitatory neurotransmitter and other neurotransmitters that are involved in the synaptic transmission of pain signals [21]. Other effective treatments include NMDA receptor agonists, such as ketamine, and antidepressants [21]. NMDA is part of the glutamatergic neurotransmitter system and is important for strong memory formation through the strengthening of synapses [22]. Thus, the NMDA receptor agonists, such as ketamine, assist in dissociative processes, which essentially “removes” a person from their body and assists in pain relief [23]. Additionally, antidepressants may be used to treat the cognitive and behavioral deficits that result from chronic pain, such as depression and anxiety. 

Although the use of antidepressants are being studied in order to better treat chronic pain, both come with certain negative side effects. For example, ketamine has side effects such as hallucinations, panic attacks, memory defects, nausea, and cardiovascular stimulation [24]. Additionally, antidepressants may have negative side effects such as loss of appetite, dizziness, headaches, stomach aches, etc. [25]. 

Despite the widespread use of drugs to treat pain, chronic pain patients have typically developed tolerance to most drugs or have developed symptoms of addiction as a result of long-term dependence [8]. Thus, other treatments are needed in addition to or to supplement pharmacotherapies.

Psychotherapies

When dealing with chronic pain that can affect day-to-day life, one may experience depression, anxiety, and/or stress due to the constant pain. Although many chronic pain treatments have historically been either physical or drug treatments, there also are multiple treatments that aim to treat the psychological effects of chronic pain. Due to psychological aspects of chronic pain, psychotherapies are being developed in order to target the emotional and mental aspects of chronic pain. These treatments have also resulted due to the ineffectiveness of medical treatments, specifically the use of opioids to treat chronic pain. There are many other treatments that are being developed in order to address chronic pain besides pharmacological and psychological treatments. This includes repetitive transcranial magnetic stimulation (rTMS) and virtual reality. 

One treatment that has been used is rTMS, which is a noninvasive brain stimulation technique that alters brain activity through electrical stimulation [21]. This technique specifically targets the primary motor cortex to reduce pain. For neuropathic pain, which is characterized by overexcitability of its neurons, rTMS may modulate these pathways by triggering inhibitory neural pathways at the dorsal horn [31]. For a variety of disorders such as major depressive disorder and Parkinson’s, rTMS has been used to reduce depressive symptoms, which is often why it is used to treat some aspects of chronic pain [31]. In general, although rTMS may be deemed effective for short-term pain relief, the long-term relief provided by rTMS has yet to be fully investigated by researchers [31]. 

Most treatments of chronic pain involve encouraging the patient to go out of their body and think about their pain in a different way. Virtual reality does this in a similar, but more hands-on way. Although virtual reality is a form of cognitive-behavioral therapy, it uses new technology known as EaseVRx which is specifically geared towards targeting both acute and chronic pain [32]. This is an immersive experience where a patient is engaged in a new environment where they will learn more about their pain and better understand the sources of it. Another virtual reality technology, known as Oculus Rift DK2, was also shown to be effective in pain relief [33].

There are four main types of psychotherapies that have been developed: cognitive behavioral therapy (CBT), mindfulness and meditation, biofeedback, and acceptance and commitment therapy (ACT) [26].

First, CBT is based on the idea that negative thinking patterns can be changed to improve coping with psychological problems, such as chronic pain [27]. CBT can be used to change the way a person is perceiving their pain and improve coping mechanisms [28]. CBT may involve “homework” where the patient must keep track of their thoughts during a painful experience [28]. It’s essentially a guided approach that encourages a person to think differently about their pain. 

Next, mindfulness and meditation are common psychotherapy practices used to treat a multitude of disorders [29]. Meditation creates a heightened state of awareness and relaxation that decreases stress and reduces pain, anxiety, and depression [29]. This is where an individual focuses on their breathing and their thoughts while they are breathing [29]. By doing this, the individual can learn to utilize breathing techniques to decrease feelings of stress and anxiety. In comparison, mindfulness involves focusing on the present and observing what your thoughts are in the moment that you are currently experiencing [29]. For example, when a patient experiences pain, they are meant to adjust their feelings and focus on the pain itself instead of their perception of it [29]. 

To continue, biofeedback addresses a person’s ability to take control of their responses to their pain [26]. A therapist will teach you different ways in which you can relax your brain and muscles while observing these changes in your heart rate, blood pressure, and sometimes brain waves, on a monitor [26]. 

Lastly, acceptance and commitment therapy (ACT) is all about making goals and moving forward [26]. This therapy emphasizes management of symptoms, reducing stress and anxiety, and improving problem-solving skills [26]. This treatment was found to be effective in getting patients to accept their pain and finding ways to enjoy life while still living with the pain [30].

Other Treatments

There are many other treatments that are being developed in order to address chronic pain besides pharmacological and psychological treatments. This includes repetitive transcranial magnetic stimulation (rTMS) and virtual reality. 

One treatment that has been used is rTMS, which is a noninvasive brain stimulation technique that alters brain activity through electrical stimulation [21]. This technique specifically targets the primary motor cortex to reduce pain. For neuropathic pain, which is characterized by overexcitability of its neurons, rTMS may modulate these pathways by triggering inhibitory neural pathways at the dorsal horn [31]. For a variety of disorders such as major depressive disorder and Parkinson’s, rTMS has been used to reduce depressive symptoms, which is often why it is used to treat some aspects of chronic pain [31]. In general, although rTMS may be deemed effective for short-term pain relief, the long-term relief provided by rTMS has yet to be fully investigated by researchers [31]. 

Most treatments of chronic pain involve encouraging the patient to go out of their body and think about their pain in a different way. Virtual reality does this in a similar, but more hands-on way. Although virtual reality is a form of cognitive-behavioral therapy, it uses new technology known as EaseVRx which is specifically geared towards targeting both acute and chronic pain [32]. This is an immersive experience where a patient is engaged in a new environment where they will learn more about their pain and better understand the sources of it. Another virtual reality technology, known as Oculus Rift DK2, was also shown to be effective in pain relief [33].

Conclusion

Despite the complicated and damaging history of the treatment of pain, several advances have been made to target it. Chronic pain is incredibly difficult to treat because there is no universal symptoms list for those dealing with pain. The neurological and physiological criteria of chronic pain is incredibly complex and still has yet to be completely understood. As of now, the simplistic 1-10 pain rating scale is used to treat most cases of pain, but researchers and doctors are finding this to be an ineffective method of treating and diagnosing pain. Thus, within the field of precision medicine, researchers are finding new ways to observe patients' reactions to treatments with the use of fMRI as well as different biomarkers [34]. There is hope for the future of treating pain, but what researchers have discovered, as a result of the opioid crisis, is that there is not one way to treat it. Therefore, with the development of psychological, pharmacological, and physiological approaches, there is a bright future for pain.

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