The precise cause of fibromyalgia in not known, but research suggests it is related to a problem with the central nervous system's processing of pain. As with some other chronic pain conditions, people with fibromyalgia often develop a heightened response to stimuli, experiencing pain that would not cause problems in other people. Yet, unlike many other pain syndromes, there is no physical evidence of inflammation or central nervous system damage.



As mentioned above, the current theory regarding the reason fibromyalgia causes its symptoms is that there is hypersensitization of the central nervous system. Pain signals are transmitted more frequently than they should be.

Recently, anticonvulsant drugs such as gabapentin (Neurontin) and pregabalin (Lyrica) have been used to reduce the level of this excess firing.

Neuronal activity in the brain can be modified by the presence of excitatory or inhibitory neurotransmitters, which exist in balance in the nervous system. The ratio of these chemicals determines how likely it is that a neuron will fire. Two major excitatory neurotransmitters are amino acids: glutamate and aspartate. Two main inhibitory neurotransmitters are glycine, another amino acid, and GABA (gamma aminobutyric acid), a derivative of glutamate. The excitatory chemicals increase the charge of neurons, while inhibitory ones make the neurons more negatively charged (less likely to fire).

When neurons fire, they release other neurotransmitters like serotonin and dopamine. This means that the decrease in serotonin levels often seen in FM patients could possibly be a result of altered GABA function. The excitatory/inhibitory neurotransmitter balance acts as a master regulator of the sensitivity of the nervous system.

Many anticonvulsant drugs-drugs used to treat epilepsy- lead to an increase in GABA signaling by inhibiting firing. Derivatives of the common anticonvulsant valproic acid (Depakote) alter levels of GABA in the brain. Tiagabine (Gabitril) and progabide (Gabrene) are also agonists of GABA receptors, meaning they bind to and activate these receptors which are located on neurons (nerve cells). This is also the mechanism of action for benzodiazepines, such as clonazepam (Klonapin).

Lyrica and Neurontin, are GABA analogs, meaning they resemble GABA enough to function the same way in the nervous system.

In a recent double-blind study sponsored by the National Institute of Arthritis Musculoskeletal and Skin Diseases, researchers found that those taking gabapentin at dosages of 1,200 to 2,400 mg daily for 12 weeks displayed significantly less pain than those taking placebo. Patients taking gabapentin also reported significantly better sleep and less fatigue. For the majority of participants, the drug was well tolerated. The most common side effects included dizziness and sedation, which were mild to moderate in severity in most cases.

Although gabapentin has little, if any, effect on acute pain, it has shown a robust effect on pain caused by a heightened response to stimuli related to inflammation or nerve injury in animal models of chronic pain syndromes.

Recent evidence also points toward a beneficial effect also occurring from the use of Lyrica in FM.

The dose required for effectiveness in fibromyalgia for both gabapentin (Neurontin) as well as pregabalin (Lyrica)is generally much higher than the dose required for anti-seizure activity. This is particularly true for Lyrica.