How Withdrawal Generates Physiologic Signals

Week 3 of the Withdrawal Symptoms Series

How reduced inhibitory stability during benzodiazepine withdrawal can activate body systems and generate signals throughout the body.

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Recognizing the Experience

Many people experiencing benzodiazepine withdrawal notice a wide range of physical sensations throughout the body.

These sensations may include palpitations, breathing discomfort, muscle tension, internal vibrations, dizziness, digestive changes, temperature sensitivity, or unusual sensory experiences.

One of the most confusing aspects of withdrawal is that these sensations often seem to come from many different body systems at once.

A person might experience heart-related symptoms at one time, digestive symptoms at another, and sensory or muscle-related symptoms at a different time.

This raises an important question: Where do these sensations come from during withdrawal?

In the previous article, we explained how the brain senses signals from the body through interoceptive pathways.

Before the brain can detect these sensations, signals must first be generated within the body.

Changes in Inhibitory Stability

As discussed in the first article, benzodiazepines increase the brain’s calming signals through GABA.

Over time, the brain adapts by adjusting the balance between calming and activating signals.

When benzodiazepines are reduced or stopped, this balance can temporarily shift.

As a result, inhibitory stability is reduced, and some neural circuits may become more reactive.

This does not mean the nervous system is damaged or not functioning. It means these systems are temporarily more active and responsive.

When this happens, body systems can become more active at the same time.

This increased activity can lead to the generation of more signals throughout the body, which the brain later detects as sensations or symptoms.

Activation of Body Systems

When inhibitory stability decreases, several body systems involved in normal regulation may become more active at the same time.

These systems help control functions such as heart rate, breathing, digestion, sensory processing, and muscle activity.

Examples include systems that regulate:

• heart and blood flow

• breathing

• digestion

• sensory signals from the body

• muscle tension and movement

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These systems are normally tightly coordinated by the nervous system to maintain stability.

When inhibitory regulation is reduced, activity across several systems can increase at the same time.

Within the Five-Axis Stress Biology Framework™, these signals can arise from several interacting domains of brain–body regulation.

These include systems involved in:

• arousal and threat signaling (Axis 1),

• excitatory–inhibitory balance (Axis 2),

• autonomic regulation (Axis 3),

• motor and muscle activation (Axis 4), and

• immune signaling (Axis 5).

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Because these systems are constantly interacting, changes in one system can influence activity in others.

As a result, signaling can increase throughout the body during withdrawal.

Signals Generated Throughout the Body

As body systems become more active during benzodiazepine withdrawal due to reduced inhibitory stability, they generate more signals across the body.

These signals can reflect changes in heart activity, breathing, digestion, muscle tension, or sensory activity within the body.

For example:

• Changes in heart function may produce signals related to heart rhythm or blood pressure

• Changes in breathing may produce signals related to airflow or chest movement

• Increased muscle activity may produce signals related to tension or internal movement

• Sensory receptors in the body may produce signals related to temperature, pressure, or internal sensations

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These signals are part of normal communication between the body and the brain.

The nervous system continuously monitors these signals to maintain balance.

During withdrawal, increased activity across multiple systems generates more signals throughout the body, increasing the overall flow of information to the brain.

Signals Travel to the Brain

Once signals are generated within body systems, they are sent to the brain through sensory pathways that monitor the body’s internal state.

Signals from internal organs travel mainly through the vagus nerve, while signals from muscles and other tissues travel through spinal pathways.

These signals pass through the brainstem and are then sent to higher brain regions that monitor the body.

As a result, the brain is constantly receiving information about what is happening throughout the body.

From Signals to Symptom Experience

When signaling within body systems increases, more signals are sent to the brain.

Signals that would normally remain below awareness may now become noticeable sensations.

For example:

• Increased heart activity may be experienced as palpitations

• Changes in breathing may produce sensations of air hunger or chest tightness

• Increased muscle activity may produce sensations of tension or internal vibration

• Sensory signals may be experienced as tingling, vibrations, burning sensations, or dizziness

Importantly, these experiences reflect the brain detecting real signals generated within the body.

Understanding this step helps explain why withdrawal symptoms can arise across many different body systems.

When several systems generate more signals at the same time, the brain may detect a wide range of physical sensations.

Diagram

Figure 3. Generation of signals during benzodiazepine withdrawal.

Reduced inhibitory stability can increase activity across multiple body systems, generating signals that travel to the brain through sensory pathways.

Looking Ahead

If withdrawal increases signaling throughout the body, another important question follows: Why do these signals sometimes feel so strong?

In the next article, we will explain how changes in neural regulation can increase the gain of these signals.

This process can amplify signals traveling from the body to the brain, making them feel more intense and noticeable.

Understanding this step helps explain why withdrawal symptoms can sometimes feel stronger than expected, even when the underlying changes in the body are relatively small.

Selected Scientific References

1. Nutt, D. J., & Malizia, A. L. (2001). New insights into the role of the GABAA–benzodiazepine receptor in psychiatric disorder. The British Journal of Psychiatry, 179(5), 390-396.

2. Craig, A. D. (2002). How do you feel? Interoception: the sense of the physiological condition of the body. Nature Reviews Neuroscience, 3(8), 655–666.

3. Sterling, P. (2012). Allostasis: A model of predictive regulation. Physiology & Behavior, Allostasis and Allostatic Load, 106(1), 5–15.