Effects of 2 Different Doses of Pregabalin on Morphine Consumption and Pain After Abdominal Hysterectomy: A Randomized, Double-Blind Clinical Trial

Yücel, Aytaç; Öztürk, Erkut; Aydoğan, M. Said; Durmuş, Mahmut; Çolak, Cemil; Ersoy, M. Özcan

doi:10.1016/j.curtheres.2011.06.004

Cited by 29 publications

(34 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…induced hyperalgesia and opioid consumption in patients 43,44 through a largely unknown mechanism. Although the therapeutic action of gabapentinoids, including gabapentin and pregabalin, is mediated by α2δ-1 binding, 23,26,35 gabapentinoids have no effect on the interaction between α2δ-1 and voltage-gated Ca 2+ channel α1 subunits or voltage-gated Ca 2+ channel activity in neurons and cell lines.…”

Section: Discussionmentioning

confidence: 99%

α2δ-1–Bound N-Methyl-d-aspartate Receptors Mediate Morphine-induced Hyperalgesia and Analgesic Tolerance by Potentiating Glutamatergic Input in Rodents

Deng

Chen

et al. 2019

Anesthesiology

View full text Add to dashboard Cite

Background: Chronic use of μ-opioid receptor agonists paradoxically causes both hyperalgesia and the loss of analgesic efficacy. Opioid treatment increases presynaptic N-methyl-d-aspartate receptor activity to potentiate nociceptive input to spinal dorsal horn neurons. However, the mechanism responsible for this opioid-induced activation of presynaptic N-methyl-d-aspartate receptors remains unclear. α2δ-1, formerly known as a calcium channel subunit, interacts with N-methyl-d-aspartate receptors and is primarily expressed at presynaptic terminals. This study tested the hypothesis that α2δ-1-bound N-methyl-d-aspartate receptors contribute to presynaptic N-methyl-d-aspartate receptor hyperactivity associated with opioid-induced hyperalgesia and analgesic tolerance.Methods: Rats (5 mg/kg) and wild-type and α2δ-1-knockout mice (10 mg/kg) were treated intraperitoneally with morphine twice/day for 8 consecutive days, and nociceptive thresholds were examined. Presynaptic N-methyl-d-aspartate receptor activity was recorded in spinal cord slices. Coimmunoprecipitation was performed to examine protein-protein interactions.Results: Chronic morphine treatment in rats increased α2δ-1 protein amounts in the dorsal root ganglion and spinal cord. Chronic morphine exposure also increased the physical interaction between α2δ-1 and N-methyl-d-aspartate receptors by 1.5 ± 0.3 fold (means ± SD, P = 0.009, n = 6) and the prevalence of α2δ-1-bound N-methyl-d-aspartate receptors at spinal cord synapses. Inhibiting α2δ-1 with gabapentin or genetic knockout of α2δ-1 abolished the increase in presynaptic N-methyl-d-aspartate receptor activity in the spinal dorsal horn induced by morphine treatment. Furthermore, uncoupling the α2δ-1-Nmethyl-d-aspartate receptor interaction with an α2δ-1 C terminus-interfering peptide fully reversed morphine-induced tonic activation of N-methyl-d-aspartate receptors at the central terminal of primary afferents. Finally, intraperitoneal injection of gabapentin or intrathecal injection of an α2δ-1 C terminus-interfering peptide or α2δ-1 genetic knockout abolished the mechanical and thermal hyperalgesia induced by chronic morphine exposure and largely preserved morphine's analgesic effect during 8 days of morphine treatment.conclusions: α2δ-1-Bound N-methyl-d-aspartate receptors contribute to opioid-induced hyperalgesia and tolerance by augmenting presynaptic N-methyl-d-aspartate receptor expression and activity at the spinal cord level. What We Already Know about This Topic• Presynaptic N-methyl-d-aspartate receptors contribute to opioid tolerance and hyperalgesia as well as neuropathic pain • The α2δ-1 protein subunit enhances presynaptic N-methyl-daspartate receptor activity What This Article Tells Us That Is New• Using mouse and rat models, it was demonstrated that α2δ-1 is essential for the increase in presynaptic N-methyl-d-aspartate receptor activity seen during chronic morphine exposure • Inhibiting α2δ-1 activity using gabapentin or genetically deleting the gene coding for α2δ-1 results in diminished o...

show abstract

Section: Discussionmentioning

confidence: 99%

α2δ-1–Bound N-Methyl-d-aspartate Receptors Mediate Morphine-induced Hyperalgesia and Analgesic Tolerance by Potentiating Glutamatergic Input in Rodents

Deng

Chen

et al. 2019

Anesthesiology

View full text Add to dashboard Cite

show abstract

“…0.71 [-1.18, -0.23] Heterogeneity: Tau 2 = 0.17; Chi 2 = 10.61, df = 6 (P = 0.10); I 2 = 43% Test for overall effect: Z = 2.91 (P = 0.004) Heterogeneity: Tau 2 = 0.52; Chi 2 = 105.20, df = 18 (P < 0.00001); I 2 = 83% Test for overall effect: Z = 4.16 (P < 0.0001) Heterogeneity: Tau 2 = 0.74; Chi 2 = 163.74, df = 14 (P < 0.00001); I 2 = 91% Test for overall effect: Z = 3.25 (P = 0.001) Heterogeneity: Tau 2 = 0.65; Chi 2 = 321.89, df = 40 (P < 0.00001); I 2 = 88% Test for subgroup differences: Chi 2 = 0.11, df = 2 (P = 0.95); I 2 = 0% Test for overall effect: Z = 5. 51 Test for overall effect: Z = 1.28 (P = 0.20) Heterogeneity: Tau 2 = 0.29; Chi 2 = 94.68, df = 22 (P < 0.00001); I 2 = 77% Test for overall effect: Z = 3.14 (P = 0.002) Heterogeneity: Tau 2 = 0.28; Chi 2 = 66.36, df = 14 (P < 0.00001); I 2 = 79% Test for overall effect: Z = 2.02 (P = 0.04) . VAS pain scores at 3 months at rest were investigated in three studies 7 9 13 and during movement in two studies 7 9 with no statistically significant differences between the groups.…”

Section: Secondary Outcomesmentioning

confidence: 99%

“…51 57 studies. Pooled results showed a statistically significant reduction in pain scores at rest [MD (95% CI)¼ 20.81 (21.07, 20.51, I 2 ¼88%)] and during movement [MD (95% CI)¼ 20.58 (20.94, 20.21, I 2…”

mentioning

confidence: 99%

Impact of pregabalin on acute and persistent postoperative pain: a systematic review and meta-analysis

Mishriky

Waldron

Habib

2015

British Journal of Anaesthesia

304

234

View full text Add to dashboard Cite

We performed this systematic review to assess the analgesic efficacy of perioperative pregabalin. Subgroup analyses and meta-regression were performed to assess the impact of individual dose and frequency of pregabalin administration on analgesic efficacy. We included 55 studies. When all doses and administration regimens were combined, pregabalin was associated with a significant reduction in pain scores at rest and during movement and opioid consumption at 24 h compared with placebo {mean difference [95% confidence interval (CI)]=-0.38 (-0.57, -0.20), -0.47 (-0.76, -0.18), and -8.27 mg morphine equivalents (-10.08, -6.47), respectively}. Patients receiving pregabalin had less postoperative nausea and vomiting and pruritus compared with placebo [relative risk (RR) (95% CI)=0.62 (0.48, 0.80) and 0.49 (0.34, 0.70), respectively]. Sedation, dizziness, and visual disturbance were more common with pregabalin compared with placebo [RR (95% CI)=1.46 (1.08, 1.98), 1.33 (1.07, 1.64), and 3.52 (2.05, 6.04), respectively]. All doses of pregabalin tested (≤75, 100-150, and 300 mg) resulted in opioid sparing at 24 h after surgery. There were no significant differences in acute pain outcomes with pregabalin 100-300 mg between single preoperative dosing regimens and those including additional doses repeated after surgery. Data were insufficient to reach conclusions regarding persistent pain, but limited data available from two studies suggested that pregabalin might be effective for the reduction of neuropathic pain. In conclusion, this review suggests that pregabalin improves postoperative analgesia compared with placebo at the expense of increased sedation and visual disturbances.

show abstract

“…A group of studies done on patients who underwent hysterectomy like that done by Ittichaikulthol et al [16] , Yücel et al [17] and Fassoulaki et al [18] as well as many studies done in 2014 like that of Chotton et al [19] , Eman et al [20] and George et al [21] . All these studies had found a significant post-operative reduction in VAS-100 score in patients who took different dose regimens of oral pregabalin (75-150 mg) in comparison with those who took any post-operative NSAID analgesic or placebo, which went in accordance with the current study.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of pregabalin as adjuvant analgesia to diclofenac sodium in laparotomies for benign gynaecological diseases: A randomized controlled trial

Tharwat

Ghanem

El-Habian

2019

Evidence Based Women's Health Journal

View full text Add to dashboard Cite

Background: Abdominal surgeries are considered one of the most painful among all types of surgeries. About 70% of patients who had abdominal surgeries suffered from severe pain in the postoperative period especially the gynaecological one. This pain as well as fatigue is the two key causes of prolonged convalescence following abdominal surgery. In order to relieve pain and fatigue, a current predominant approach of multimodal postoperative analgesia is used, mostly based on a combination of opioids, non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol and perioperative administration of local anesthetics. Each of these different approaches has its own set of complications. Objective: The current study aimed to assess the efficacy of oral pregabalin 150 mg as adjuvant analgesic to i.v diclofenac sodium 75mg. Patients and Methods: A randomized controlled trial was done on female patients who had laparotomies for benign gynaecological diseases in Ain Shams University Maternity Hospital during duration of nine months. The trial included one hundred and sixteen patients, divided into two equal groups. The first group (group A) received oral pregabalin 150 mg with i.v diclofenac sodium 75 mg one hour before operation and 12 hours after operation and was repeated every 12 hours for the first 24 hours and/or in demand. The second group (group B) received intravenous diclofenac sodium 75 mg 12 hours after operation and was repeated every 12 hours for the first 24 hours and/or in demand. The primary objective is measuring pain six hours postoperative and every one hour by using VAS-100 score, the secondary objective is measuring patient ambulation and audible intestinal sounds 6 hours postoperative. Results: Pain perception was significantly lower among group A than group B. As on VAS study group record of 20-10, control group record 45-30. Analgesia-free time was significantly lower among study than among control by 2 hours. Side effects were more frequent among study than among control group, but the differences were significant only in somnolence. This study showed also a significant early post-operative mobilisation in those who took oral pregabalin 150 mg in comparison to those who took i.v diclofenac sodium 100 mg that is attributed to decrease pain perception. It revealed also no significant difference between both groups regarding the intestinal activity. Conclusion: Administration of oral pregabalin 150 mg preoperatively reduce post-operative pain following abdominal gynecological operation, decrease the need of usage of post-operative narcotic analgesic, early patient mobilization that finally improve the surgical outcome and the patient quality of life.

show abstract

Effects of 2 Different Doses of Pregabalin on Morphine Consumption and Pain After Abdominal Hysterectomy: A Randomized, Double-Blind Clinical Trial

Cited by 29 publications

References 20 publications

α2δ-1–Bound N-Methyl-d-aspartate Receptors Mediate Morphine-induced Hyperalgesia and Analgesic Tolerance by Potentiating Glutamatergic Input in Rodents

α2δ-1–Bound N-Methyl-d-aspartate Receptors Mediate Morphine-induced Hyperalgesia and Analgesic Tolerance by Potentiating Glutamatergic Input in Rodents

Impact of pregabalin on acute and persistent postoperative pain: a systematic review and meta-analysis

Efficacy of pregabalin as adjuvant analgesia to diclofenac sodium in laparotomies for benign gynaecological diseases: A randomized controlled trial

Contact Info

Product

Resources

About