Effects of 2 different doses of pregabalin on morphine consumption and pain after abdominal hysterectomy a randomized double blind clinical trial

Abstract

Pain relief after surgical procedures continues to be a major medical challenge. Alleviation of pain has been given a high priority by medical professionals and health authorities. Improvement in perioperative analgesia is not only desirable for humanitarian reasons but also essential for its potential to reduce postoperative morbidity and mortality.1,2 Unsatisfactory analgesia increases discomfort of the patient and prolongs hospital stay.3 This means an increase in the incidence of complications and treatment costs.3 Moreover, it may lead to development of chronic pain as an adverse effect, one of the most devastating problems related to this issue if acute pain cannot be treated as required.4 Postoperative pain is not purely nociceptive in nature and may consist of inflammatory, neurogenic, and visceral components.5 Sensitization of the dorsal horn neurons has been demonstrated in acute pain models and may also play a role in the development of chronic pain after surgery.6 By reducing the hyperexcitability of dorsal horn neurons induced by tissue damage, gabapentin and pregabalin may have roles in the treatment of postoperative pain.7,8 Pregabalin is the pharmacologically active S-enantiomer of 3-aminomethyl-5- methyl-hexanoic acid.9 It is a structural analogue of -aminobutyric acid, one of the key inhibitory neurotransmitters in the brain. Its mode of action is believed to be mediated by the -2--1 subunit protein of voltage-gated calcium channels, resulting in its anxiolytic, anticonvulsant, and antinociceptive effects.10 Pregabalin is rapidly absorbed with peak blood concentrations occurring within 1 hour. The average bioavailability exceeds 90% and is independent of dose, which may produce a more predictable patient response. The elimination half-life of pregabalin ranges between 5.5 and 6.7 hours and is independent of dose.9,11 Due to these specific properties of pregabalin, preoperative single dose administration is effective in postoperative pain therapy with no need for long-term treatment.12 Although opioids continue to have an important role in postoperative pain management, they have side effects.13,14 For this reason, multimodal analgesia was suggested to improve postoperative analgesia and to reduce opioid-related side effects.15 An antineuropathic pain drug like pregabalin, as a part of multimodal analgesia, can be useful for optimization of postoperative analgesia.7,8,12,16 Early preclinical studies suggesting analgesic efficacy after tissue injury led to the development of gabapentin and pregabalin as treatments for postoperative pain.17,18 Preoperative administration of 600 mg pregabalin, but not 300 mg, significantly reduced opioid usage in patients after laparoscopic hysterectomy.7 In addition, a study reported that 75 and 150 mg doses of pregabalin did not reduce postoperative