Effects of oral pregabalin and aprepitant on pain and central sensitization in the electrical hyperalgesia model in human volunteers
ABSTRACT 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.
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.
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.
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.
SourceAvailable from: Alireza Mahoori[Show abstract] [Hide abstract]
ABSTRACT: Introduction: Post-dural puncture headache (PDPH) is a common complication of lumbar puncture for any purpose. To avoid the need for invasive methods of treating PDPH such as blood patch, the search for novel pharmacological agents to manage PDPH continues. The aim of this study was to compare the effects of acetaminophen, gabapentin and pregabalin in controlling PDPH in patients who underwent surgery under spinal anesthesia. Materials and Methods: A total of 90 patients who underwent elective orthopedic surgery under spinal anesthesia and suffered from PDPH consequently were enrolled in this randomized trial. Patients were categorized randomly into three groups. Group A, B and C have received Acetaminophen, Gabapentin and Pregabalin (3 times a day for 3 days), respectively. The effect of medications on the severity of PDPH was evaluated and compared using visual analog scale (VAS). Results: The mean VAS score was significantly lower in pregabalin group compared with others 24, 48 and 72 h after the onset of headache (P = 0.001 for all of them) and lower in Gabapentin group compared with Acetaminophen group 24, 48 and 72 h after the onset of headache (P = 0.001 for all analyses). No adverse outcome was reported in groups. Conclusion: Pregabalin and gabapentin are both useful and safe in management of PDPH, but pregabalin is more effective in this regard.07/2014; 8(3):374-7. DOI:10.4103/1658-354X.136436
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ABSTRACT: This double-blind, placebo-controlled, three-period cross-over, four treatment option, incomplete block study (ClinicalTrials.gov number NCT01485185), with an adaptive design for sample size re-estimation, was designed to evaluate gabapentin plus donepezil in an established experimental model of electrical hyperalgesia. Thirty healthy male subjects aged 18-55 years were randomized to receive gabapentin 900 mg or gabapentin 900 mg + donepezil 5 mg for two of the three treatment periods, with 50% of subjects randomized to receive placebo (negative control) and 50% to gabapentin 1800 mg (positive control) for the remaining period. Each treatment period was 14 days. Gabapentin or corresponding placebo was administered on Day 13 and the morning of Day 14. Donepezil or corresponding placebo was administered nocturnally from Day 1-13 and the morning of Day 14. Co-primary endpoints were the area of pin-prick hyperalgesia (260 mN von Frey filament) and allodynia (stroking by cotton bud) evoked by electrical hyperalgesia on Day 14. Gabapentin 1800 mg (n=14) significantly reduced the area of allodynia versus placebo (n=14) (-12.83 cm(2) [95% CI -23.14, -2.53], p=0.015) with supportive results for hyperalgesia (-14.04 cm(2) [-28.49, 0.41], p=0.057), validating the electrical hyperalgesia model. Gabapentin+donepezil (n=30) significantly reduced the area of hyperalgesia versus gabapentin 900 mg (n=30) (-11.73 cm(2) [-21.04, -2.42], p=0.014), with supportive results for allodynia (-6.62 cm(2) [-13.29, 0.04], p=0.052). The adverse event profile for gabapentin+donepezil was similar to the same dose of gabapentin. Data are supportive of further clinical investigation of a gabapentin and donepezil combination in patients with an inadequate response to gabapentin.Pain 09/2014; 155(12). DOI:10.1016/j.pain.2014.09.003 · 5.84 Impact Factor
Journal of Anaesthesiology Clinical Pharmacology 09/2009; 25(3):321-326.