Should Parecoxib be added to Pregabalin regimens?

Inhibitors of Cox 2 (cyclooxygenase 2, related to the prostaglandin pathways) may improve the reduction in allodynia from pregabalin. We are receiving so many reports of edema, swelling, and other side effects, we are not sure pregabalin (Lyrica) will prove to be of widespread use in central pain at the required doses. However, in view of the interest over it, we mention related information. Again, always rely on your personal doctor–this site does NOT dispense medical advice–it is for educational purposes only.

Chizh et al, writing in Br J Anaesth. 2007 Feb;98(2):246-54 found that the effects of oral pregabalin were potentiated by parecoxib.

Prior studies in animal models, as well as humans, have shown benefit from Pregabalin for nerve injury pain. (see review of Phil Siddall’s work in Australia using SEARCH at this site).

Pfizer, who manufactures pregabalin has given it the trade name of “Lyrica”.

As you know from reading prior articles, central sensitization is considered to be a valid area for enlightening us on central pain. Central sensitization is still being defined, but basically it is along the lines of Pat Wall’s famous dictum, “peripheral injury induces central change”. By comparison, central Pain would be “central injury induces central change”. Central sensitization is not as severe as central pain, but significant pain can be caused by it.

In this study the British authors used a model involving continual electric shocks to the skin, inducing a type of central sensitization. This condition was treated with pregabalin, which yielded some reduction in “the areas of punctate mechanical hyperalgesia and dynamic touch allodynia vs placebo”. However, when a Cox 2 inhibitor, Parecoxib, was added, pregabalin was even more effective for central sensitization from electroshock.

In this study, when aprepitant, an inhibitor of Neurokinin 1 (NK1) was used, no reduction in allodynia was obtained. NK1 is released at the synapse by Substance P, a known pain neurotransmitter, so this casts a little doubt on whether these findings can be directly applied to central pain, where much study, by Merck in particular, is being conducted to try to effect blockade of substance P.

Mantyh and Malmberg have already shown that killing cells receptive to Substance P stops central pain in rats, so we cannot say that this work is complete. Perhaps soon a study will be performed along the same lines in central pain.