Chizh, B. A. et al. Effects of oral pregabalin and aprepitant on pain and central sensitization in the electrical hyperalgesia model in human volunteers. Br. J. Anaesth. 98, 246-254

Clinical Pharmacology and Discovery Medicine, GlaxoSmithKline, Addenbrooke's Centre for Clinical Investigation, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2GG, UK.
BJA British Journal of Anaesthesia (Impact Factor: 4.85). 03/2007; 98(2):246-54. DOI: 10.1093/bja/ael344
Source: PubMed


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.

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Available from: Andreas Tröster, Feb 04, 2016
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    • "Some studies have demonstrated that a clinically useful effective dose of oral pregabalin inhibits central sensitization of electrical hyperalgesia in human volunteers. It seems that pregabalin, which has been effective in reducing hyperalgesia, may play an important role in acute post-operative pain control.[19] "
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    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.
    Full-text · Article · Jul 2014
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    • "be due to the actions of pregabalin as analgesic, anti-hyperalgesic , and anxiolytic [11] [12], the main mechanism of action pregablin is through blocking the development of hyperalgesia and central sensitization, and it binds to the a2-d_ subunit of voltage-gated calcium channels with binding affinity six times more than that of gabapentin, reducing the release of excitatory neurotransmitters including glutamate, noradrenaline, serotonin, dopamine, and substance P. Additionally, it also produces an inhibitory modulation of neuronal excitability in areas of the central nervous system dense in synaptic connections as the neocortex, amygdala, and hippocampus [12] [13] [14]. Zencirci [7] reported that oral pregabalin 150 mg/day reduced the severity of postdural puncture headache in two females who did not respond to conventional treatments with oral paracetamol and caffeine (300 mg/day), bed rest and hydration and 200 mg intravenous theophylline infusion for 36 h with no recorded side effects except sedation. "
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    ABSTRACT: Objective The aim of this study was to evaluate the efficacy of prophylactic pregabalin on postdural puncture headache incidence and severity after spinal anesthesia. Method 86 ASA I-II male and female patients age 20–50 years old, undergoing elective general surgeries below the umbilicus under spinal anesthesia with 3 ml heavy bupivacaine 0.5% (15 mg), patients were randomly allocated into one of two groups (Group C, n = 43) (control group) received a placebo capsule 2 h preoperatively (Group P, n = 43) received 150 mg pregabalin capsule 2 h preoperatively, number of attempts for spinal block, sensory level, motor block grade, postoperative time to first analgesic requirement, the incidence, onset and intensity of PDPH and adverse events were recorded for 72 h. Results The peak sensory level in C group and P group showed no statistical significant difference, the time to peak sensory block was significantly earlier in P group than group C, the time to reach the modified Bromage motor block grade 3 was significantly earlier in P group than C group, time to two segment regression of sensory level to S1 and motor block regression to modified Bromage grade 0 were statistically insignificant between the studied groups. Group P had a significantly longer time to first analgesic requirements than group C, and there was no significant difference in VAS (visual analogue scale) of pain between the studied groups. There was significant increase in sedation score in P group compared to C group at 2 h and 6 h postoperatively, and there was statistically significant reduction in the incidence rate and severity of PDPH in P group compared to group C. There were no recorded cases of dizziness, visual disturbances, or PONV. Conclusions preoperative oral pregabalin 150 mg reduced the incidence and severity of PDPH, beside the earlier onset of peak sensory and motor block with increase duration of analgesia in patients undergoing elective surgeries under spinal anesthesia.
    Full-text · Article · Oct 2013 · Egyptian Journal of Anaesthesia
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    • "Nowadays, pregabalin is utilized in reducing neuropathic and even inflammatory pain, tissue irritation, neuralgia and fibromyalgia. We have taken into account the lesser side effects of pregabalin and its effect on acute and chronic pain, therefore it seems that this drug can be efficient in controlling mild to moderate pain of the patients after surgeries (11-15). Dacryocystorhinostomy (DCR) is among the surgeries that cause mild to moderate pain and administering opioids to relieve this level of postoperative pain leads to respiratory side effects, nausea, vomiting and urinary retention especially in old age. "
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    ABSTRACT: Postoperative pain of dacryocystorhinostomy (DCA) surgery is one of the serious issues to be considered. Administrating opioids to relieve postoperative pain and facing their increasing side effects in eye surgeries, make the use of non-opioid drugs inevitable. The present study examined the efficacy of pregabalin in alleviating the postoperative pain of DCA surgery. The present study has been carried out as a double-blind, randomized clinical trial on the patient candidates for DCR. The patients were randomly divided in to two groups of pregabalin and placebo. Patients in pregabalin group received 300 mg of pregabalin, an hour before the operation in the morning of the surgery. Pain intensity on visual analog scale (VAS) was recorded until 24 hours after the operation; also the rate of administrated opioids and nausea/vomiting frequency were recorded during the first 24-hour period after the operation and the resultsof the two groups were compared. Postoperative pain intensity in the pregabalin group at the time of recovery was significantly lower than that of the placebo group (P = 0.001) until 24 hours after the surgery. In the pregabalin group 17.5% of the patients received opioids while in the placebo group the figure was 52.5% (P = 0.001). Nausea frequency was also higher in the placebo group than the pregabalin group (P = 0.003). A single 300 mg dose of pregabalin, an hour before DCA can effectively reduce pain intensity and also reduce opioid dose and nausea/vomiting.
    Full-text · Article · Sep 2012 · Anesthesiology and Pain Medicine
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