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Cited by 193Anesthesia and Pain ManagementPain Mechanisms and TreatmentsPain Management and Opioid Use

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Perioperative Gabapentinoids: Choice of Agent, Dose, Timing, and Effects on Chronic Postsurgical Pain

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Schmidt, Peter C., Ruchelli, Gabriela, Mackey, Sean C., Carroll, Ian R.·2013·Anesthesiology
DOI 10.1097/aln.0b013e3182a9a896
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Abstract

T HE gabapentinoids pregabalin and gabapentin are both indicated for the treatment of postherpetic neuralgia and as adjuvant therapy for seizure disorders.Pregabalin is additionally approved for the treatment of fibromyalgia and neuropathic pain associated with diabetes mellitus or spinal cord injury.There are now more than 100 clinical trials examining the use of gabapentin perioperatively to reduce postoperative pain and a smaller but growing number of clinical trials examining the efficacy of pregabalin.As a body of work, they support the conclusion that perioperative use of gabapentinoids reduces early postoperative pain and opioid use.[1][2][3] This article describes how this body of work may inform a surgeon's or anesthesiologist's optimization of perioperative use of gabapentinoids, including choice of agent, dose, timing, and duration of therapy.In addition, we described the less clear data for and against gabapentinoid efficacy in preventing the emergence of chronic postsurgical pain. Mechanisms of Action, Pharmacokinetics, and Adverse EffectsAlthough both of the gabapentinoids are structural analogs of γ-aminobutyric acid, neither has any activity at the γ-aminobutyric acid receptors (fig.1).Instead, they bind to the α-2δ subunit of presynaptic P/Q-type voltage-gated calcium channels, modulating the traffic and function of these channels.This in turn is thought to modulate the subsequent release of excitatory neurotransmitters from activated nociceptors.4 By modulating calcium-induced release of glutamate from activated pain-transmitting neurons, these drugs may inhibit pain transmission and central sensitization (fig.2).Alternatively, some evidence indicates that their antinociceptive mechanism may arise through activation of noradrenergic pain-inhibiting pathways in the spinal cord and brain.5 The principal differences between these two drugs arise not from different modes of action but rather from differing bioavailability.Although both drugs are absorbed by amino acid carriers, gabapentin absorption is limited to a relatively small part of the duodenum, whereas pregabalin is absorbed throughout the small intestine.Once the active transport of gabapentin in the duodenum is saturated, progressively higher levels of gabapentin ingestion yield progressively smaller increases in blood concentrations.Conceptually, this provides an upper border not only to efficacy but also to adverse effects.In contrast, pregabalin appears to be absorbed throughout the small intestines and demonstrates linear uptake without transporter saturation at therapeutic concentrations.6,7 Therefore, at least conceptually, pregabalin might demonstrate both increased efficacy and increased side effects in situations that require high doses.Both pregabalin and gabapentin exhibit minimal protein binding and are renally excreted without significant metabolism.Pharmacokinetic interactions are minimal, though gabapentin absorption can be significantly impaired by antacids, even when given up to 2 h after dosing.This should be considered in preoperative

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  1. 2011, Efficacy of pregabalin in acute postoperative pain: A meta-analysis., Br J Anaesth, 106, 454, 10.1093/bja/aer027 · DOI

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Metadata

Authors
Schmidt, P. C., Ruchelli, G., Mackey, S. C., & Carroll, I. R.
Affiliations
  • Clinical Instructor of Anesthesiology
  • Research Assistant
  • Professor of Anesthesiology and Pain Medicine
  • Stanford Medicine (US)
ORCID
Venue
Anesthesiology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2013-11
Volume
119
Issue
5
Pages
1215-1221
ISSN
0003-3022 (ISSN-L)
DOI
10.1097/aln.0b013e3182a9a896
OpenAlex
W2022607794
Cited by
193
References
45
Citations by year
2026: 5 · 2025: 5 · 2024: 13 · 2023: 17 · 2022: 10 · 2021: 10 · 2020: 19 · 2019: 18 · 2018: 27 · 2017: 24 · 2016: 14 · 2015: 16 · 2014: 14 · 2013: 1
FWCI
2.65
Type
journal article
Language
en
Open access
Locations
  • Anesthesiology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Pain Management
  • Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
Keywords
gabapentinoids, pregabalin, gabapentin, perioperative analgesia, postoperative pain, opioid-sparing effect, chronic postoperative pain, calcium channel modulation, pharmacokinetics, adverse effects, postherpetic neuralgia, fibromyalgia, neuropathic pain
MeSH terms
Pregabalin, Gabapentin, Amines, Analgesics, Cyclohexanecarboxylic Acids, gamma-Aminobutyric Acid, Humans, Postoperative Pain, Pain, Postoperative, Perioperative Care, Chronic Pain

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