Pregabalin is a popular medication for managing conditions ranging from chronic pain to anxiety disorders, offering effective relief to millions of people worldwide. According to the Medical Expenditure Panel Survey (MEPS), the percentage of people who used pregabalin increased from 1.2% in 2002 to 3.9% in 2015 in the USA [1]. But how does this medication actually work in your body?

In this context, we’ll explain what happens in the brain when you take Pregabalin in an easy-to-understand way so you can better understand what happens when you take this potent medication.

A Quick Overview of Pregabalin

Pregabalin is a prescription drug that has proven effective in treating various medical conditions. Its versatile therapeutic benefits have made it a subject of increasing interest among medical professionals and patients.

The United States Food and Drug Administration (FDA) approved the medical use of Pregabalin in 2004.
Pregabalin capsules are marketed under various brand names, and one of its most popular brands is Nervigesic. Nervigesic capsules, manufactured by the famous Signature Pharmaceutical, are available in the dosage strengths of  Nervigesic capsule 75 mg, 150 mg, and 300 mg.

FDA-Approved Indications
The FDA-approved indications of Pregabalin include [3] –

• Management of postherpetic neuralgia
• Management of fibromyalgia
• Management of neuropathic pain associated with spinal cord injury
• Management of neuropathic pain associated with diabetic peripheral

neuropathy.

• Adjunctive therapy for the treatment of partial onset seizures in patients 4 years old

of age and older.

Off-label use of a drug means prescribing a medication for a different use than what the FDA approved. Some of the off-label indications of Pregabalin are –

• Generalized anxiety disorder
• Chronic cough
• Social anxiety disorder
• Chronic pain conditions
• Restless leg syndrome
• Complex regional pain syndrome
• Uremic pruritus.

Pregabalin Mechanism Of Action Explained

Pregabalin capsules work by binding to a specific subunit of voltage-gated calcium channels in the CNS (central nervous system). These channels are crucial for releasing several neurotransmitters, including norepinephrine, glutamate, and substance P. By attaching to the alpha-2-delta subunit of these calcium channels, Pregabalin medication effectively modulates their action.

This binding decreases the calcium ion influx into nerve terminals, reducing the release of excitatory neurotransmitters.

The reduction in the release of neurotransmitters helps to stabilize neural circuits that can be active excessively in conditions like neuropathic pain and epilepsy. In epilepsy, this stabilization can help prevent the abnormal electrical discharges in the brain that cause seizures. For neuropathic pain, the reduced release of neurotransmitters like glutamate and substance P can decrease the abnormal pain signaling that often characterizes this condition.

Pregabalin is also known for its anxiolytic properties, which make it effective for treating generalized anxiety disorder. Although the exact working mechanisms are not clear, it is thought that the modulation of calcium channels and the subsequent reduction in the neurotransmitter release may also play a role in its ability to alleviate the symptoms of anxiety.

By lowering the hyperactivity in neural circuits that are often associated with anxiety, Pregabalin can produce a calming effect.

Another aspect of Pregabalin’s mechanism is its rapid absorption and high bioavailability when administered orally. This ensures that the medication can quickly reach effective concentrations in the bloodstream and the CNS, where it exerts its effects. This pharmacokinetic profile of Pregabalin contributes to its efficacy in various therapeutic uses [4].

Pregabalin’s Effects For Pain, Anxiety, and Epilepsy

Neuropathic Pain

Neuropathic pain is nerve pain caused if your nervous system gets damaged or malfunctions. You can feel pain from any of the various levels of your nervous system, including your spinal cord, brain, and peripheral nerves.

According to preclinical and clinical studies by Vivek Verma and colleagues, Pregabalin is very effective for neuropathic pain control and has an excellent safety profile [5].

In another study, Victor Mayoral et al.’s Pregabalin vs. Gabapentin in treating neuropathic pain found that Pregabalin is more effective than Gabapentin in reducing neuropathic pain [6].

Anxiety

Anxiety is described as a feeling of uneasiness, dread, and fear. But if your anxiety does not go away or gets worse with time, then it is called an anxiety disorder.

A research study by David S Baldwin and colleagues stated that Pregabalin is effective in alleviating the severity of physical and psychological symptoms of anxiety, in reducing sleep disturbance, and in reducing the severity of coexisting depressive symptoms, and is also beneficial as a second-line treatment in patients who have not responded to treatment with SSRI or SNRI antidepressants.

Epilepsy

Epilepsy is a persistent brain disorder in which a group of nerve cells, or neurons, sometimes sends wrong signals, causing seizures. During a seizure, many neurons send signals simultaneously, much faster than normal. This surge of electrical activity may cause involuntary sensations, movements, emotions, or behaviors.

A clinical study by Christian E. Elger et al., published in 2005, concluded that administering Pregabalin twice daily (600 mg daily) was highly effective and well-tolerated as add-on therapy for partial seizures. When dosing was individualized to optimize effectiveness and tolerability, fewer side effects and discontinuations were achieved in individuals receiving Pregabalin.

Conclusion

To conclude, Pregabalin’s working mechanism provides insight into how it reduces symptoms of conditions like epilepsy, anxiety, and neuropathic pain. By modulating voltage-gated calcium channels, reducing neurotransmitter release, and stabilizing neural circuits, Pregabalin capsules offer effective relief from the symptoms of anxiety, epilepsy, and pain.

Pregabalin comes with the risk of side effects; therefore, we advise you to take this medication only under the careful supervision of your healthcare provider.