Lyrica (pregabalin) treatment of fibromyalgia – how it works?

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Quick Look

Why does Lyrica (pregabalin) reduce the pain of fibromyalgia?

Science: Pregabalin reduces the ability of substance P to activate NF-kappaB.

Conclusion: Pregabalin may reduce fibromyalgia pain in part by inhibiting NF-kappaB activation, leading to a reduction in pro-inflammatory cytokines.


Substance P

Fibromyalgia is associated with increased levels of “substance P” – a neurotransmitter and neuromodulator that is found in the brain and spinal cord.

Substance P is associated with inflammatory processes and especially with pain processes. It increases pain transmission and pain sensitivity.


Lyrica (Pregabalin)

Pregabalin is used in the treatment of seizure, neuropathic pain and fibromyalgia. It is thought to act by binding to a specific receptor on nerve cells and reducing or slowing nerve transmissions in the central nervous system.

Effect on substance P

In this study it was shown that Lyrica (pregabalin) limits the ability of substance P to activate NF-kB in cancer cells. It seems reasonable to suspect that this effect is not specific to cancer cells, and that pregabalin reduces substance P mediated activation of NF-kB in many different cell types.

Effect on NF-kappaB

NF-kB acts as a sort of ‘master switch’ in controlling inflammation. Therefore, by limiting substance P activation of NF-kB, pregabalin might exert at least a mild anti-inflammatory effect, and would definitely exert such an effect in relation to substance P.

Possible mechanism of action

Given that pregabalin’s (Lyrica’s) mechanism of action in fibromyalgia is unknown, could it be that the actual benefit of pregabalin in the treatment of fibromyalgia is it’s ability to reduce the inflammation caused by substance P? That seems possible, perhaps even likely.

Suggesting a possible alternative

An alternative approach might be to use natural inhibitors of NF-kB, whereby it might be possible to achieve a similar or perhaps greater effect while avoiding what is the actual intended effect of pregabalin – the reduction of nerve impulses in the CNS.

Pregabalin and gabapentin inhibit substance P-induced NF-kappaB activation in neuroblastoma and glioma cells.

Summary of the abstract

Pregabalin and gabapentin are lipophilic amino acids that show anticonvulsant and analgesic activity against neuropathic pain.

Their actions on substance P-induced NF-kB activation were investigated in human neuroblastoma and rat glioma cells and in both cases they were found to inhibit NF-kB activation.

These drugs also inhibited NF-kB activation in rat spinal dorsal root ganglia cells pre-treated with substance P, suggesting a previously undefined role for pregabalin.

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