Research Review: Chronic Pain as an Emergent Property of a Complex System & the Potential Roles of Psychedelic Therapies
A recent study offers a fresh perspective on pain by applying the lens of complexity science to chronic pain. We review the study's key points and discuss how psychedelic therapies may offer promising solutions.
Chronic pain remains a persistent and often debilitating issue for millions worldwide, defying many conventional treatments. Despite numerous research advances and the attention of global health organizations, clinical outcomes for chronic pain sufferers have seen minimal improvement.
A recent study, “Chronic pain as an emergent property of a complex system and the potential roles of psychedelic therapies," offers a fresh perspective by applying the lens of complexity science to chronic pain. Read on for a summary of key points...
Understanding Chronic Pain as a Complex System
Chronic pain is traditionally categorized into three types: nociceptive, neuropathic, and nociplastic. Nociceptive pain relates to tissue damage and inflammation, neuropathic pain arises from damage to neural tissues, and nociplastic pain persists without any clear tissue damage.
The study suggests viewing chronic pain through the lens of complexity science, which sees it as an emergent property of an intricate biopsychosocial system. This system includes various interacting components like pain-related physiology, neuroscience, developmental psychology, learning, and epigenetics.
FIGURE 1. Proposed schematic representing interacting components and mini-systems. Central arrows represent multidirectional interactions among internal components. As incoming data are processed, their influence and interpretation are affected by many system components, including others not depicted in this simple graphic, via Frontiers
Components of the Chronic Pain System, Viewing Through the Lens of Complexity Science:
In this system, we can see that the “traditional” categorization of pain is just a small piece of the entire pain puzzle. The following factors all contribute:
Physiological Factors
Nociceptive Pain: Originates from tissue damage or inflammation, causing a normal response in an intact somatosensory system.
Neuropathic Pain: Arises from a demonstrable lesion or disease in neural tissue, leading to pain.
Nociplastic Pain: Persists without identifiable tissue damage, representing the most complex and least understood category of pain.
Neuroendocrine Factors
Hypothalamic-Pituitary-Adrenal (HPA) Axis: Involves neuroendocrine cells that respond to stress, illness, and injury by releasing glucocorticoids, influencing learning and potentially contributing to chronic pain.
The HPA axis plays a crucial role in the body's response to stress, illness, and injury. When the body encounters stress, the hypothalamus releases corticotropin-releasing hormone (CRH), which signals the pituitary gland to release adrenocorticotropic hormone (ACTH).
ACTH then stimulates the adrenal glands to produce glucocorticoids, such as cortisol. Cortisol helps manage stress by regulating various bodily functions, including metabolism and immune response. Chronic activation of the HPA axis can lead to dysregulation, contributing to the persistence of chronic pain by affecting learning, memory, and sensitivity to pain.
Immune System Factors
Microglia: Brain-resident macrophages that regulate neuronal function and behavior, contributing to neuroinflammation and neuroprotection. Their activation states can influence chronic pain.
Microglia are the primary immune cells of the central nervous system, acting as brain-resident macrophages. They are involved in maintaining homeostasis, responding to injury, and regulating neuronal function and behavior. In their activated state, microglia can contribute to neuroinflammation, a significant factor in chronic pain. Microglia can polarize into pro-inflammatory (M1) or anti-inflammatory (M2) states, influenced by the microenvironment. Activated microglia release neurotrophic factors that affect neuronal excitability, long-term potentiation, and synaptic efficacy, playing a role in the persistence of chronic pain
Mast Cells: Central nervous system cells associated with neuroinflammation and pain, affecting the microenvironment and behavior of microglia.
Mast cells are associated with allergic reactions and also exist within the central nervous system. They contribute to neuroinflammation and pain by affecting the microenvironment and interacting with other immune cells, including microglia.
Brain Networks
Default Mode Network (DMN): Involved in self-referential thought and goal-independent activity, influencing chronic pain perception.
Salience Network (SN): Detects and responds to novel, relevant stimuli, playing a role in pain-related vigilance and anxiety.
Central Executive Network (CEN/FPN): Engages in goal-oriented activities, with changes in connectivity potentially contributing to cognitive disability in chronic pain.
Interoceptive Dysfunction
Interoception: Sensing and registering the body's internal state, including afferent signaling and centrally mediated representation of physiological states. Perturbations can lead to overinterpretation of pain signals and greater distress.
Cognitive and Emotional Factors
Central Sensitization: Involves increased membrane excitability and neural recruitment, leading to amplification of pain signals and cognitive-emotional sensitization.
Learning and Memory: Stress and pain engage learning circuits in the hippocampus, amygdala, and prefrontal cortex, affecting behavior and potentially leading to chronic pain through processes like fear extinction failure and negative reinforcement learning.
Epigenetic Factors
Epigenetics: Persistent changes in gene expression without altering DNA sequence, influencing chronic pain through mechanisms like methylation and histone modifications. These changes can be triggered by early life trauma or adverse experiences.
The Role of Psychedelics in Chronic Pain Management
From a complexity science perspective, chronic pain may benefit from therapies that can be both disruptive and adaptive. Psychedelic-assisted therapies are posited as potentially effective due to their ability to disrupt rigid cognitive, emotional, and behavioral patterns, promoting neuroplasticity in the process.
Psychedelics, such as psilocybin, LSD, and MDMA, have been shown to influence major brain networks involved in chronic pain, including the default mode network (DMN), the salience network (SN), and the central executive network (CEN/FPN). These networks are key to self-referential thought, detecting novel stimuli, and goal-oriented activities, respectively. Dysregulation in these networks is linked to chronic pain, and psychedelics may help by promoting more flexible and adaptive network interactions.
Mechanisms of Psychedelics’ Action: Disruption and Adaptation
Psychedelics can create "destabilization" within the brain's functional architecture, allowing for new, healthier patterns to emerge. This process is akin to melting a rigid metal, making it malleable for reshaping. By relaxing entrenched, maladaptive neural connections and promoting new ones, psychedelics can help reset the brain's pain perception and response mechanisms.
Furthermore, psychedelics have been shown to enhance neuroplasticity, the brain's ability to reorganize itself by forming new neural connections. This is crucial for unlearning maladaptive pain responses and fostering new, healthier patterns of thinking and behavior. The study highlights that the integration of psychedelic experiences with supportive therapies, such as mindfulness and cognitive-behavioral therapy, may optimize these benefits.
Implications for Chronic Pain Treatment
The study proposes that treating chronic pain requires an approach that acknowledges its complexity. Psychedelic therapies, when combined with other holistic treatments, could address the multifaceted nature of chronic pain more effectively than traditional, reductionist approaches.
Embracing the Bio-Psycho-Social Model
As a practitioner deeply committed to the bio-psycho-social model of health, I believe that treating the patient as a whole person is essential. This model emphasizes the interconnection of biological, psychological, and social factors in health and illness. Chronic pain, viewed through this lens, is not merely a physical ailment but a complex interplay of these dimensions.
Psychedelic-assisted therapies align well with this holistic approach. They offer a means to address not just the physical aspects of pain but also the psychological and social dimensions that contribute to its persistence and severity. By facilitating deep, transformative experiences and fostering a more adaptive brain state, psychedelics can help patients reframe their relationship with pain and promote overall well-being.
The complexity of chronic pain calls for innovative and multifaceted treatment approaches. Psychedelic therapies hold unique promise in this regard, offering both disruptive and adaptive potential to reset and rewire the brain's pain pathways. If you are interested in exploring how psychedelic therapies, such as ketamine, can support your chronic pain management within a holistic, bio-psycho-social framework, please contact NeuroPain Health.
Read the full study here.
If you or a loved one is curious about how ketamine-assisted therapy could support you, contact us today.