The Limbic System, Oxytocin, and Pain Management

The Limbic System

The limbic system is a complex set of structures in the midbrain that includes the hypothalamus, hippocampus, amygdala, and the cingulate cortex.¹ The components that make up the limbic system are responsible for “feeling and reacting” in the brain and are responsible for the formation of memories and assigning emotional significance to human senses. The limbic system is also closely integrated with the immune, endocrine, and autonomic nervous systems. Inflammation and physical trauma are two factors of many that can alter the functionality of the limbic system.¹ When the limbic system is not functioning appropriately due to injury or impairment, it becomes hypersensitive and begins to react to stimuli that are typically disregarded. This is a threat to the body and can result in inappropriate activation of the immune, endocrine, and autonomic nervous systems.¹ The over-firing of protection and threat mechanisms in the midbrain leads to distorted unconscious reactions, sensory perception, and protective responses. Over time, this state of hyperarousal can weaken the immune system, and affect systems associated in rest, digestion, detoxification, mood stability, and motor and cognitive function.¹

The hypothalamus is the primary output node for the limbic system and is responsible for sexual function, endocrine function, behavioral function, and autonomic control. Notably, endocrine functions are controlled by either direct axonal connection to the posterior pituitary (vasopressin and oxytocin) or via secretion into the hypothalamic-hypophyseal portal system.

The Role of the Limbic System in Pain Perception

The limbic system, and more specifically the amygdala, is an important area of the brain for modulating the amount of pain experienced for a given noxious stimulus. The latero-capsular division of the central nucleus of the amygdala has been described as the “nociceptive amygdala” and appears to act at different levels of the pain neuraxis to both facilitate and inhibit pain modulation.² Since the limbic system is the center where emotions are processed, this component of the brain is heavily intertwined with pain recognition and management.² Pain is merely a “signal” that there is something wrong in the body; however, once this “signal” reaches the brain, the emotional center, hosted by the limbic system, transforms the “signal” into a response and pain is thus felt. The emotional response to pain involves the anterior cingulate gyrus and the right ventral prefrontal cortex.³

Limbic System Retraining for Pain Management

One school of thought is that limbic system retraining can be a useful non-pharmacologic modality for pain management to reverse hyperstimulation and depressed protective response. As with many disease states, non-pharmacological management is preferred as first-line therapy over medication- based treatments. Since chronic pain is often non-specific and widespread, pharmacologic-directed therapy is often difficult to utilize when there is not a clearly defined targeted source of pain.⁴

Limbic system retraining is a mechanism-targeted behavioral intervention that combines cognitive behavior therapy with emotional, behavioral, and cognitive restructuring along with neural linguistic reprogramming. The goal of limbic retraining is to reverse the maladaptive stress response and recover the necessary thoughts, emotions, and behavior patterns for the body to appropriately process stress and pain responses. Retraining the limbic system relies heavily on a psychological and neurophysiological approach to process pain signals that have been mismanaged by the emotional response.⁵ This approach is patient-intensive, differing from traditional pharmacotherapy- directed therapies. For effective results, the patient must be compliant, as intermittent treatment is not as effective in redirecting the brain’s maladaptive perception of painful stimuli.

Limbic system retraining is minimally documented in the literature, and more robust studies are needed to provide evidence-based recommendations on its effectiveness. Tinnitus retraining therapy has been shown to be successful in multiple published studies and relies heavily on limbic system retraining. Just as the limbic system and auditory systems are highly integrated, the limbic system and pain perception are directly related.⁶ With tinnitus, it is not the auditory perception that is problematic but the presence of inappropriate associations between tinnitus-related neuronal activity and the reactions of the limbic and autonomic nervous systems. Therefore, in pain management, retraining the limbic system to recognize pain signals can lead to appropriate reactions of the limbic system and revive the protective mechanisms that can aid in the perception of pain.⁶

Limbic system retraining is a complex and labor-intensive psychological therapy. Its long-term utility requires more controlled studies. Pharmacological adjuvants may act synergistically to improve the process in terms of efficiency and effectiveness. Oxytocin may be one such compound that mechanistically is poised to fill this void.