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      Gabapentinoids: Gabapentin and Pregabalin for Postoperative Pain Management

      editorial

      1 , 1 , *

      Anesthesiology and Pain Medicine

      Kowsar

      Pregabalin, Gabapentin, Pain

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          Abstract

          Editorial Postsurgical pain is normally perceived as nociceptive pain. Surgical trauma has been known to induce central and peripheral sensitization and hyperalgesia, which in untreated cases could lead to chronic postoperative pain after surgery. Indeed pain is one of the three most common medical causes of delayed discharge after ambulatory surgery, the other two being drowsiness and nausea/ vomiting. Antihyperalgesic drugs improve postoperative pain by preventing the development of central sensitization (1). The development of newer agents available for postoperative pain control create possibilities for better combinations in multimodal analgesia. The recent advances in postoperative pain management can be specifically grouped in the following areas: Finding exact molecular mechanisms, new pharmaceutical products and other routes and modes of analgesic delivery. For the years, opioids have been the mainstay of postoperative pain management but they have side effects. For this purpose the multimodal approach and non-opioid drugs have been suggested to improve postoperative analgesia and to reduce opioid related side effects (2). Gabapentinoids (gabapentin and pregabalin) were originally introduced as antiepileptics but have analgesic, anticonvulsant, and anxiolytic effects also. These easily tolerable drugs by patients have limited side-effects. Gabapentin an anti-epileptic drug binds to the alpha-2 delta subunit of the presynaptic voltage gated-calcium channels and inhibits calcium release so prevents the release of excitatory neurotransmitters involved in the pain pathways (2, 3). Gabapentin has demonstrated analgesic effect in diabetic neuropathy, post-herpetic neuralgia, and neuropathic pain. Several meta-analyses reveal that perioperative gabapentin helps to produce a significant opioid-sparing effect and probably decreses postoperative pain score relative to the control group (4, 5). Pregabalin is a structural analog of gamma-aminobutyric acid (GABA). It acts by presynaptic binding to the α -2-λ subunit of voltage-gated calcium channels that are widely distributed in the spinal cord and brain6. By this mechanism, pregabalin modulates the release of several excitatory neurotransmitters, such as glutamate, norepinephrine, substance P, and calcitonin gene-related peptide. It leads to inhibitory modulation of “overexcited” neurons and returning them to a “normal” state. Centrally, pregabalin could reduce the hyperexcitability of dorsal horn neurons that is induced by tissue damage (6). To sum up, pregabalin has a more appropriate pharmacokinetic profile than gabapentin, including dose-independent absorption and far more potent than gabapentin while producing fewer adverse effects (7-9). Pregabalin has efficacy of varying degree in neuropathic pain conditions such as postherpetic neuralgia, painful diabetic neuropathy, central neuropathic pain, and fibromyalgia. While some surveys do not demonstrate a significant analgesic effect in the acute, including postoperative pain control (9, 10), other studies suggest pregabalin to have effective sedative and opioid-sparing effects (11-13), and emphasize on its effectiveness in acute pain control. Since safe postoperative pain control is nessecary, established role of pregabalin as an analgesic adjuvant as a part of multimodal analgesia for acute pain control is in progress (7, 8, 14, 15). Its unique potency in reducing opioid requirements, prevention of opioid tolerance, enhancement the quality of opioid analgesia, decreased respiratory depression and anxiolysis, make it an attractive drug to consider for control of pain in the post-operative setting (15-17). Lots of meta-analyses and clinical trials show that perioperative pregabaline helps to produce a significant opioid-sparing effect and probably improves postoperative pain score relative to the control group (18-21). Having looked at these two drugs from different angles and aspects, one comes to this understanding that these multi-purpose drugs have found a strong and reliable place in acute pain service setting. So, Gabapentinoids are an effective tool in the treatment of postoperative pain.

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          Most cited references 19

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          Pregabalin for acute and chronic pain in adults.

          Antiepileptic drugs have been used in pain management since the 1960s. Pregabalin is a recently developed antiepileptic drug also used in management of chronic neuropathic pain conditions. To assess analgesic efficacy and associated adverse events of pregabalin in acute and chronic pain. We searched MEDLINE, EMBASE, and CENTRAL to May 2009 for randomised controlled trials (RCTs). Additional studies were identified from the reference lists of retrieved papers and on-line clinical trial databases. Randomised, double blind trials reporting on the analgesic effect of pregabalin, with subjective pain assessment by the patient as either the primary or a secondary outcome. Two independent review authors extracted data and assessed trial quality. Numbers-needed-to-treat-to-benefit (NNTs) were calculated, where possible, from dichotomous data for effectiveness, adverse events and study withdrawals. There was no clear evidence of beneficial effects of pregabalin in established acute postoperative pain. No studies evaluated pregabalin in chronic nociceptive pain, like arthritis.Pregabalin at doses of 300 mg, 450 mg, and 600 mg daily was effective in patients with postherpetic neuralgia, painful diabetic neuropathy, central neuropathic pain, and fibromyalgia (19 studies, 7003 participants). Pregabalin at 150 mg daily was generally ineffective. Efficacy was demonstrated for dichotomous outcomes equating to moderate or substantial pain relief, alongside lower rates for lack of efficacy discontinuations with increasing dose. The best (lowest) NNT for each condition for at least 50% pain relief over baseline (substantial benefit) for 600 mg pregabalin daily compared with placebo were 3.9 (95% confidence interval 3.1 to 5.1) for postherpetic neuralgia, 5.0 (4.0 to 6.6) for painful diabetic neuropathy, 5.6 (3.5 to 14) for central neuropathic pain, and 11 (7.1 to 21) for fibromyalgia.With 600 mg pregabalin daily somnolence typically occurred in 15% to 25% and dizziness occurred in 27% to 46%. Treatment was discontinued due to adverse events in 18 to 28%. The proportion of participants reporting at least one adverse event was not affected by dose, nor was the number with a serious adverse event, which was not more than with placebo.Higher rates of substantial benefit were found in postherpetic neuralgia and painful diabetic neuropathy than in central neuropathic pain and fibromyalgia. For moderate and substantial benefit on any outcome NNTs for the former were generally six and below for 300 mg and 600 mg daily; for fibromyalgia NNTs were much higher, and generally seven and above. Pregabalin has proven efficacy in neuropathic pain conditions and fibromyalgia. A minority of patients will have substantial benefit with pregabalin, and more will have moderate benefit. Many will have no or trivial benefit, or will discontinue because of adverse events. Individualisation of treatment is needed to maximise pain relief and minimise adverse events. There is no evidence to support the use of pregabalin in acute pain scenarios.
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            Do surgical patients benefit from perioperative gabapentin/pregabalin? A systematic review of efficacy and safety.

            Gabapentin and pregabalin have antiallodynic and antihyperalgesic properties useful for treating neuropathic pain. These properties may also be beneficial in acute postoperative pain. In this study we evaluated randomized, controlled trials examining the analgesic efficacy, adverse effects, and clinical value of gabapentinoids in postoperative pain. A systematic search of Medline, PubMed, and Cochrane Central Register of Controlled Trials (CENTRAL) databases yielded 22 randomized, controlled trials on perioperative administration of gabapentinoids for postoperative pain relief. Pain relief was better in the gabapentin groups compared with the control groups. The opioid-sparing effect during the first 24 h after a single dose of gabapentin 300-1200 mg, administered 1-2 h preoperatively, ranged from 20% to 62%. The combined effect of a single dose of gabapentin was a reduction of opioid consumption equivalent to 30 +/- 4 mg of morphine (mean +/- 95% CI) during the first 24 h after surgery. Metaregression analysis suggested that the gabapentin-induced reduction in the 24-h opioid consumption was not significantly dependent on the gabapentin dose. Gabapentin reduced opioid-related adverse effects, such as nausea, vomiting, and urinary retention (number-needed-to-treat 25, 6, and 7, respectively). The most common adverse effects of the gabapentinoids were sedation and dizziness (number-needed-to-harm 35 and 12, respectively). Gabapentinoids effectively reduce postoperative pain, opioid consumption, and opioid-related adverse effects after surgery. Conclusions about the optimal dose and duration of the treatment cannot be made because of the heterogeneity of the trials. Studies are needed to determine the long-term benefits, if any, of perioperative gabapentinoids.
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              Auxiliary subunits: essential components of the voltage-gated calcium channel complex.

              Voltage-gated calcium channels are important mediators of several physiological processes, including neuronal excitability and muscle contraction. At the molecular level, the channels are composed of four subunits--the pore forming alpha(1) subunit and the auxiliary alpha(2)delta, beta and gamma subunits. The auxiliary subunits modulate the trafficking and the biophysical properties of the alpha(1) subunit. In the past several years there has been an acceleration of our understanding of the auxiliary subunits, primarily because of their molecular characterization and the availability of spontaneous and targeted mouse mutants. These studies have revealed the crucial role of the subunits in the functional effects that are mediated by voltage-gated calcium channels.
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                Author and article information

                Journal
                Anesth Pain Med
                Anesth Pain Med
                10.5812/aapm
                Kowsar
                Anesthesiology and Pain Medicine
                Kowsar
                2228-7523
                2228-7531
                13 September 2012
                Autumn 2012
                : 2
                : 2
                : 52-53
                Affiliations
                [1 ]Department of Anesthesiology and Pain Medicine, Iran University of Medical Sciences, Tehran, IR Iran
                Author notes
                [* ]Corresponding author: Poupak Rahimzadeh, Department of Anesthesiology and Pain Medicine, Iran University of Medical Sciences, Tehran, IR Iran. Tel: +98-9121064483, Fax: +98-2166509059, E-mail: p-rahimzadeh@ 123456tums.ac.ir .
                Article
                10.5812/aapm.7743
                3821114
                24223337
                Copyright © 2012, Iranian Society of Regional Anesthesia and Pain Medicine

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Editorial

                pregabalin, gabapentin, pain

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