Effects of oral pregabalin and aprepitant on pain and central sensitization in t

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Br J Anaesth. 2007 Feb;98(2):246-54.

Effects of oral pregabalin and aprepitant on pain and central

sensitization in the electrical hyperalgesia model in human

volunteers.

Chizh BA, Gohring M, Troster A, Quartey GK, Schmelz M, Koppert W.

Clinical Pharmacology and Discovery Medicine, GlaxoKline,

Addenbrooke's Centre for Clinical Investigation, Addenbrooke's

Hospital, Hills Road, Cambridge CB2 2GG, UK.

BACKGROUND: /st> Central sensitization is an important mechanism of

neuropathic pain; its human models could be useful for early

detection of efficacy of novel treatments. The electrical

hyperalgesia model invokes central sensitization by repetitive

stimulation of the skin. To assess its predictive value, we have

investigated pregabalin, a standard neuropathic pain treatment, and

aprepitant, an NK(1) antagonist, as an example of a drug class

active in animal models but not in neuropathic pain patients.

Furthermore, we explored if combinations of either of these drugs

with the COX-2 inhibitor parecoxib could improve its efficacy.

METHODS: /st> This was a double-blind, two-period, placebo-

controlled study using incomplete block design. Thirty-two healthy

volunteers received either oral pregabalin (titrated to 300 mg) or

aprepitant (titrated to 320 mg), or matching placebo over 6 days

before testing. Sensitization was assessed over 3 h; at 2 h,

subjects received either parecoxib (40 mg) or saline i.v.

RESULTS: /st> Pregabalin significantly reduced the areas of punctate

mechanical hyperalgesia and dynamic touch allodynia vs placebo (both

P < 0.0001); no significant reduction in the area of hyperalgesia or

allodynia vs placebo was observed with aprepitant. In the pregabalin

+ parecoxib treated group, the area of allodynia was significantly

reduced (P < 0.0001) and the area of hyperalgesia insignificantly

attenuated (P = 0.09) vs placebo + parecoxib; no efficacy

improvement was observed with aprepitant + parecoxib.

CONCLUSIONS: /st> The model can serve to predict analgesic efficacy

in early human development and investigate the mechanism of action.

The model could also be used to explore efficacy of analgesic

combinations to provide a rationale for patient studies.