The Hidden Mechanisms of Chronic Pain: Insights from Neuroscience

When you're in pain, your immediate instinct is to alleviate it. Whether you're reaching for over-the-counter medications, applying heat or ice, or avoiding physical activity altogether, you're acting on the belief that pain directly reflects tissue damage. While this understanding holds true for acute pain, it doesn't apply in the same way to chronic pain. Recognizing this distinction is essential for both individuals experiencing chronic pain and the practitioners who work with them.

Chronic pain is not typically a symptom of injury or tissue damage; rather, it is a complex, multifaceted condition involving various bodily systems. It can persist long after an initial injury has healed or arise without any detectable damage at all. To navigate this complexity and effectively manage chronic pain, we must explore the intricate interplay between the nervous, immune, and endocrine systems.

Nociception and Ascending Pathways

When most of us think of pain, we envision a noxious stimulus initiating a nervous signal up to the brain. It’s nowhere near that simple, but it’s good to start with that image to define some basic terms. The noxious stimulus is converted into a nervous signal by a nociceptor, and the process of signaling from nociceptor to brain is referred to as nociception. The neural pathway that carries this signal is known as the ascending pathway.

Descending Modulation: The Brain’s Role in Pain Control

One of the most critical concepts to grasp regarding chronic pain is descending modulation, which refers to neural signals that descend from the brain and brainstem to the spinal cord to intercept and alter the activity within the ascending pathway before it moves up to the brain.

Descending modulation operates like a volume dial: it can either diminish nociception (Descending Inhibition) or amplify it (Descending Facilitation). The neurochemistry of descending inhibition involves dopamine, norepinephrine, and cannabinoids, which is why individuals with chronic pain frequently receive prescriptions for medications that target these neurochemicals.

Descending inhibition is what is responsible for placebo effects. Without the influence of descending pathways, the phenomenon of placebo wouldn’t exist. Placebo is often perceived as a mysterious phenomenon, a sort of mind-over-matter magic. However, we need not divide reality into mind and matter to understand how placebo works. Instead, we can think of it as the brain influencing the spinal cord through tangible neuronal communication.

When descending modulation functions effectively, it can significantly lessen pain intensity. However, in individuals with chronic pain, descending pathways fail to inhibit ascending signals. For instance, individuals with fibromyalgia frequently show reduced activation of descending inhibitory pathways, resulting in chronic, widespread pain. Knowing this, we see how important it is to implement treatments that boost these descending signals.

Sensitization

Understanding pain mechanisms also requires that we learn about sensitization. Sensitization involves changes in nociception that lead to hyper-responsiveness, including peripheral sensitization (heightened nociceptor response) and central sensitization (hypersensitivity in the CNS).

Peripheral sensitization occurs through an increase in nociceptor counts, a decrease in their activation thresholds, and the release of inflammatory substances from the same nociceptive neurons that are activated, which subsequently stimulates additional nociceptors. While peripheral sensitization is a normal response to injury, it can also arise from various immune responses and psychosocial factors.

Central sensitization encompasses a broad range of processes occurring within the CNS. Similar to peripheral sensitization, it involves reduced activation thresholds, which means that signals that typically wouldn't reach the brain are relayed onward instead. It also involves the loss of spinal interneurons that usually modulate and filter nociceptive activity; their loss can result in a breakdown of this regulation, leading to disarray in the system.

The Interplay of Sensitization and Descending Modulation

Descending modulation and sensitization are distinct yet closely interacting processes. Sensitization arises from a chemical soup derived from immune and endocrine responses that impact neural function. Descending modulation, on the other hand, is one part of the nervous system putting the brakes on another. While descending inhibition can mitigate the effects of sensitization, it doesn’t reduce sensitization itself. When descending inhibition is weak, the effects of sensitization can persist unchecked.

A helpful analogy is to think of sensitization as a toddler and modulation as a parent. When sensitization is low, pain is manageable; when it’s high, it’s like the toddler throwing a tantrum. Effective modulation acts as a calm parent, stepping in to modulate the situation and determine the outcome.

For individuals with chronic pain, it’s useful to determine if the condition stems from a noxious stimulus triggering nociceptors, an issue of sensitization, or a breakdown in descending inhibition. If sensitization is the culprit, the next step is to determine whether immune or endocrine factors are at play. This understanding is crucial for guiding treatment, which might involve addressing the original stimulus, reducing immune or endocrine responses, enhancing descending inhibition, or a combination of these strategies.

Of course, the specific methods for achieving these goals are a complex topic in their own right, but simply understanding these mechanisms and having a clear idea of which one is being targeted is far more effective than relying on outdated ideas or randomly trying different treatments to see what sticks. With a well-informed approach, both patients and practitioners can pursue strategies that are grounded in the current science.

Conclusion

Effectively managing chronic pain involves recognizing the critical roles of descending modulation and how the immune and endocrine systems contribute to sensitization. By addressing factors like inflammation, stress, and enhancing descending inhibition, we can significantly alter how pain is perceived. Understanding that pain is not simply a sign of tissue damage but rather the result of a complex interplay between biological systems empowers patients and provides practitioners with better tools to promote overall well-being and guide better treatment strategies.

If you’re interested in exploring these concepts further and learning how to better manage chronic pain, consider enrolling in my Neuroscience of Pain course that delves deeper into pain mechanisms and the interplay of these systems to help cultivate strategies that can improve the quality of life for chronic pain sufferers.

Author

Dr. Mark Olson holds an M.A. in Education and a Ph.D. in Neuroscience from the University of Illinois, specializing in Cognitive and Behavioral Neuropsychology and Neuroanatomy. His research focused on memory, attention, eye movements, and aesthetic preferences. Dr. Olson is also a NARM® practitioner, aquatic therapist, and published author on chronic pain and trauma-informed care.  He offers a variety of courses at Dr-Olson.com that provide neuroscientific insights into the human experience and relational skill training for professionals and curious laypersons.