Opioid-induzierte Hyperalgesie

Opioids are the drugs of choice for the treatment of moderate to severe acute and chronic pain. However, clinical evidence suggests that opioids can elicit increased sensitivity to noxious stimuli suggesting that administration of opioids can activate both pain inhibitory and pain facilitatory systems. Acute receptor desensitization via uncoupling of the receptor from G-proteins, up-regulation of the cAMP pathway, activation of the N-methyl-D-aspartate (NMDA) receptor system, as well as descending facilitation, have been proposed as potential mechanisms underlying opioid-induced hyperalgesia. Numerous reports exist demonstrating that opioid-induced hyperalgesia is observed both in animal and human experimental models. Brief exposures to micro-receptor agonists induce long-lasting hyperalgesic effects for days, which might by reflected by clinical observations that large doses of intraoperative micro-receptor agonists increased postoperative pain and morphine consumption. Furthermore, the prolonged use of opioids in patients often requires increasing doses and may be accompanied by the development of abnormal pain. Successful strategies that may decrease or prevent opioid-induced hyperalgesia include the concomitant administration of drugs like NMDA-antagonists, alpha(2)-agonists, or non-steroidal anti-inflammatory drugs (NSAIDs), opioid rotation or combinations of opioids with different receptor selectivity.     

Nonsteroidal antiinflammatory drugs and the risk of operative site bleeding after tonsillectomy: a quantitative systematic review

The use of nonsteroidal antiinflammatory drugs (NSAIDs) for analgesia after tonsillectomy is controversial because NSAIDS, through platelet inhibition, may increase the risk of perioperative bleeding. We systematically searched for randomized, controlled trials that reported on the incidence of perioperative bleeding attributable to the use of NSAIDs in patients undergoing tonsillectomy. As secondary outcome measures, we analyzed the quality of pain relief and the incidence of postoperative nausea and vomiting. Twenty-five studies with data from 970 patients receiving a NSAID and 883 receiving a non-NSAID treatment or a placebo were analyzed. Data were combined using a fixed-effect model. Of four bleeding end points (intraoperative blood loss, postoperative bleeding, hospital admission, and reoperation because of bleeding), only reoperation happened significantly more often with NSAIDs: Peto-odds ratio, 2.33 (95% confidence interval [CI], 1.12-4.83) and number-needed-to-treat, 60 (95% CI, 34-277). Compared with opioids, NSAIDs were equianalgesic, and the risk of emesis was significantly decreased (relative risk, 0.73; 95% CI, 0.63-0.85; numbers-needed-to-treat, 9; 95% CI, 5-19). IMPLICATIONS: The evidence for nonsteroidal antiinflammatory drugs to increase the risk of bleeding after tonsillectomy is equivocal, and the risk-benefit ratio is not straightforward. There is some evidence for an increased likelihood of reoperation because of bleeding. The agenda must be one of further research rather than of clinical recommendations.     

Prévention de la douleur postopératoire

The pre-emptive analgesia concept suggests that pre-administration of analgesics may enhance the efficacy of these drugs. This review has selected the data from the literature according to two types of methodological criteria: Sackett's criteria, and those specific of pre-emptive analgesia studies. Infiltration, spinal and peripheral nerve blocks using local anaesthetic drugs do not seem to produce pre-emptive analgesia. The few positive results have limited clinical significance. The results concerning opioids are contradictory and the clinical significance is limited. Preoperative oral administration of non steroidal anti-inflammatory drugs (NSAIDs) offers no benefit. Intravenous pre-administration has a limited advantage, but enhances perioperative bleeding. Kétamine, an NMDA receptor antagonist, may have some pre-emptive analgesic properties according to the few studies available. In conclusion, pre-administration of analgesic drugs represents the usual strategy for the anaesthesiologist (spinal or peripheral block, infiltration, opioids). In other cases (NSAIDs, kétamine), pre-administration represents a change in usual practice. This is not justified for NSAIDs; NMDA receptor antagonists may offer an interesting research area. Data concerning pre-emptive analgesia for chronic pain syndrome such as phantom limb pain are quite limited.     

Opioid therapy for chronic noncancer pain: practice guidelines for initiation and maintenance of therapy

Contemporary standard pharmacological care for the treatment of noncancer pain includes the use of opioid medications. The responsiveness of neuropathic pain to opioids has long been an area of controversy. Evidence from multiple randomized controlled trials indicates that opioids can relieve pain in a variety of neuropathic pain syndromes. Opioids are typically reserved for moderate to severe pain that cannot be relieved by the nonsteroidal anti-inflammatory drugs (NSAIDs). Opioids are often used in combination with other adjuvants or other analgesic agents. The advantage of opioids is the lack of a ceiling effect of the pure mu opioid agonists. The disadvantages of these drugs are a series of mechanism-based opioids-related side effects (e.g., nausea, drowsiness, constipation) and the potential issue of their abuse and misuse. Each patient needs to undergo a comprehensive evaluation and receive education on the treatment. The physician must be well conversant with the differential diagnosis and definitions of physical dependence, tolerance, pseudotolerance, aberrant behaviors, addiction, and pseudoaddiction. No specific opioid drug is intrinsically 'better' than the others. Opioid rotation refers to the switch from one opioid to another when the degree of analgesia obtained is limited by the persistence of adverse effects or the occurrence of clinically relevant tolerance. This approach is based on the observation that a patient's response varies from opioid to opioid. At present, after 1) appropriate selection of patients and 2) longitudinal patient care with routine assessment of degree of analgesia, functional daily activities, adverse events and aberrant behaviors is carried out, opioid therapy can be the safest and most effective treatment measure for quality of life improvement in the chronic pain patient.     

The impact of opioid-induced hyperalgesia for postoperative pain

Clinical evidence suggests that--besides their well known analgesic activity - opioids can increase rather than decrease sensitivity to noxious stimuli. Based on the observation that opioids can activate pain inhibitory and pain facilitatory systems, this pain hypersensitivity has been attributed to a relative predominance of pronociceptive mechanisms. Acute receptor desensitization via uncoupling of the receptor from G-proteins, upregulation of the cAMP pathway, activation of the N-methyl-D-aspartate (NMDA)-receptor system, as well as descending facilitation, have been proposed as potential mechanisms underlying opioid-induced hyperalgesia. Numerous reports exist demonstrating that opioid-induced hyperalgesia is observed both in animal and human experimental models. Brief exposures to micro-receptor agonists induce long-lasting hyperalgesic effects for days in rodents, and also in humans large-doses of intraoperative micro-receptor agonists were found to increase postoperative pain and morphine consumption. Furthermore, the prolonged use of opioids in patients is often associated with a requirement for increasing doses and the development of abnormal pain. Successful strategies that may decrease or prevent opioid-induced hyperalgesia include the concomitant administration of drugs like NMDA-antagonists, alpha2-agonists, or non-steroidal anti-inflammatory drugs (NSAIDs), opioid rotation or combinations of opioids with different receptor/selectivity.     

Sequential clot strength analyses following diclofenac in pediatric adenotonsillectomy

BACKGROUND: Tonsillectomy is a common pediatric surgical procedure resulting in significant postoperative pain. There is ongoing controversy as to the most satisfactory analgesic regimen. Nonsteroidal antiinflammatory drugs (NSAIDs) are an alternative to opioids in this setting. NSAID use in tonsillectomy has been shown to be opioid sparing in the recovery period and to have similar analgesic effects to opioids in pediatric patients. Because of their nonspecific action on the enzyme cyclo-oxygenase there is potential for increased bleeding which has led many practitioners to avoid NSAIDs completely in this patient population potentially resulting in suboptimal pain control. Our aim in this study was to assess the effect of preoperatively administered diclofenac on the blood clot strength in children undergoing (adeno-) tonsillectomy. METHODS: Twenty patients undergoing (adeno-) tonsillectomy were recruited into this prospective observational study. All patients received 2 mg.kg(-1) of diclofenac rectally immediately preoperatively. Blood was taken for thromboelastograph analysis pre-diclofenac and 1 and 4 h post-diclofenac administration. RESULTS: There was a statistically significant increase in maximal clot strength (MA) at 1 and 4 h after diclofenac. Similarly there was a statistically significant reduction in time to initial fibrin formation (R time) post-diclofenac. There was no primary or secondary hemorrhage. CONCLUSIONS: Diclofenac when given preoperatively does not adversely affect clot strength in the immediate postoperative period when the risk of primary hemorrhage is greatest.     

How to treat chronic pain in rheumatic and musculoskeletal diseases (RMDs) – A pharmacological review

IntroductionChronic pain is a common symptom of rheumatic diseases that impacts patients’ quality of life. While non-pharmacological approaches are often recommended as first-line treatments, pharmacological interventions are important for pain management. However, the effectiveness and safety of different pharmacological treatments for chronic pain in rheumatic diseases are unclear.MethodsThis review critically synthesizes the current evidence base to guide clinicians in selecting appropriate pharmacological treatments for their patients, considering the expected benefits and potential risks and side effects.ResultsFor osteoarthritis, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, opioids, and antidepressants are commonly used, with NSAIDs being the most recommended. In addition, topical agents, such as topical NSAIDs, are recommended for localized pain relief. For fibromyalgia, amitriptyline, serotonin and noradrenaline reuptake inhibitors (SNRIs), and gabapentinoids are commonly used, with SNRIs being the most recommended. For back pain, nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, opioids are used only for acute of flare-up pain, whereas neuropathic pain drugs are only used for chronic radicular pain. For inflammatory rheumatic diseases, disease-modifying antirheumatic drugs (DMARDs) and biological agents are recommended to slow disease progression and manage symptoms.ConclusionWhile DMARDs and biological agents are recommended for inflammatory rheumatic diseases, pharmacological treatments for other rheumatic diseases only alleviate symptoms and do not provide a cure for the underlying condition. The use of pharmacological treatments should be based on the expected benefits and evaluation of side effects, with non-pharmacological modalities also being considered, especially for fibromyalgia.     

Pharmacological treatment of chronic pain

Pain transmission involves numerous pathways, transmitters and receptors. This suggests that there will never be a single ‘magic bullet’ antinociceptive drug. Optimum pain control often requires a multimodal approach using several analgesics. The primary goals in managing chronic pain are to reduce pain and most importantly to improve function. The rapid control of pain symptoms can reduce the risk of chronicity.The optimal pharmacological treatment for chronic pain is that the medication should be taken ‘round the clock’ rather than ‘as required’. It is easier to keep pain at bay rather than trying to control it after it has resurfaced. The World Health Organization (WHO) 3-step analgesic ladder has proved successful in controlling over 80% of cancer pain. It is also appropriate for non-malignant nociceptive pain and uses conventional analgesic drugs. The drugs used in Step 1 are paracetamol (acetaminophen), non-steroidal anti-inflammatory drugs (NSAIDs) and cyclo-oxygenase II inhibitors (COX II). Codeine and other opioids are used for moderate pain in Step 2, and the potent opioid drugs, such as morphine, are used in Step 3. Local modulation uses the local application of transcutaneous electrical nerve stimulation (TENS), acupuncture or regional analgesic block by injection into tissue or around nerves using local anaesthetics, opioids, steroids, alpha 2 agonists (e.g. clonidine) and/or NMDA antagonists (e.g. ketamine). For neuropathic pain, adjuvant drugs such as antidepressants, anticonvulsants and antiarrhythmics are more effective. The antidepressant amitriptyline is the gold standard. Adjuvant analgesics appear to work by potentiating the dorsal inhibitory pathways of the spinal cord or stabilizing excitable neural fibres.     

Evaluation of the safety and efficacy of the perioperative administration of rofecoxib for total knee arthroplasty.

Nonsteroidal anti-inflammatory drugs (NSAIDs) frequently are discontinued before elective total knee arthroplasty (TKA) because of the increased incidence of perioperative bleeding. Rofecoxib, a selective cyclooxygenase 2 inhibitor, does not interfere with the coagulation system and may be a safer NSAID for patients undergoing TKA. In this study, 100 patients undergoing elective TKA discontinued their use of NSAIDs 10 days before surgery and were assigned randomly to receive either placebo (n = 50) or rofecoxib (n = 50), 25 mg daily for 5 consecutive days starting 3 days before surgery. The administration of rofecoxib resulted in improved preoperative pain scores and no significant increase in the incidence of perioperative bleeding or international normalized ratio compared with placebo. Rofecoxib does not need to be discontinued before elective TKA.     

Pharmacology of systemic analgesics

Systemic administration of analgesic drugs is still the most widely used method for providing pain relief in acute painful situations. Opioids may be selected on the basis of their physicochemical characteristics and their diffusion index to the brain. But in clinical practice, their very steep concentration-analgesic effect relationship remains a critical aspect of opioid therapy. Thus, small fluctuations in plasma concentrations of opioids may lead to profound fluctuations in analgesic effect when their plasma and effect-site concentrations are near the minimum effective analgesic concentration (MEAC). Combining drugs acting on different mechanisms of nociceptive modulation offers benefits from additive/synergistic effects and will decrease the incidence of their adverse effects. Evidence-based reviews showed that effective pain relief using non-opioid analgesics relied on paracetamol supplemented with non-steroidal anti-inflammatory drugs (NSAIDs). The role of COX-2 selective inhibitors (CSIs) in acute pain relief still requires further evaluation. NSAIDs, CSIs and paracetamol share the property of morphine sparing in situations of severe (post-operative) pain. CSIs may be beneficial in patients in whom post-operative bleeding is a major surgical risk as the effects of NSAIDs on coagulation may last for days. Finally, low-dose ketamine infusions remain a worthwhile addition to opioid therapy. Analgesic concentrations of ketamine are 1/5th to 1/10th the anaesthetic concentration and exert significant inhibition on N-methyl-d-aspartate (NMDA) receptor activation.     

The utility of adding symptoms and signs to the management of injury-related pain

ObjectiveImproved pain assessment and management in the emergency department (ED) is warranted. We aimed to determine the impact on pain management, of adding symptoms and signs to pain assessment.Patients and methodsA single center before-and-after study was conducted, supplemented by an interrupted time series analysis. The intervention included the addition of clinical presentation (CP) of the injury and facial expression (FE) of the patient to pain assessment scales of patients with soft tissue injures. Pain intensity was categorized as: mild, moderate, and severe. We compared types of pain relief medications, use of strong opioids, and pain relief efficacy between pre and post intervention phases.ResultsBefore-and-after analysis revealed a significant reduction in the use of strong opioids. The adjusted relative ratio for the use of strong opioids in the post intervention phase was 0.63 (95% CI: 0.48–0.82). This reduction was mostly driven by less use of strong opioids in patients reporting severe pain (from 17.3%–7.9%) (P < 0.0001). A larger proportion of patients in the post intervention phase than in the pre intervention phase received weak opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) (27.4% vs 19.1%, P = 0.002), and a larger proportion did not receive any pain relief medication (19.8% vs 10.5%, p < 0.0001). The use of strong opioids increased with higher levels of FE and CP. Among patients with mild injury and reporting severe pain, the odds of receiving a strong opioid was nearly 9 times (OR = 8.9, 95% CI: 4.0–19.6) higher among those who were with an unrelaxed FE and showed pain behavior than those with relaxed FE. Interrupted time-series analysis showed that the mean ΔVAS (VAS score at entry minus VAS score at discharge) in the post intervention phase compared with the pre intervention phase was not statistically significant (P = 0.073). The use of strong opioids in the post intervention phase was significantly reduced (P = 0.017).ConclusionAdding symptoms and signs to pain assessment of patients admitted with soft tissue injuries decreased the use of strong opioids, without affecting pain relief efficacy.     

A systematic review on the effectiveness of pharmacological interventions for chronic non-specific low-back pain

The objective of this review was to determine the effectiveness of pharmacological interventions [i.e., non-steroid anti-inflammatory drugs (NSAIDs), muscle relaxants, antidepressants, and opioids] for non-specific chronic low-back pain (LBP). Existing Cochrane reviews for the four interventions were screened for studies fulfilling the inclusion criteria. Then, the literature searches were updated. Only randomized controlled trials on adults (≥18 years) with chronic (≥12 weeks) non-specific LBP and evaluation of at least one of the main clinically relevant outcome measures (pain, functional status, perceived recovery, or return to work) were included. The GRADE approach was used to determine the quality of evidence. A total of 17 randomized controlled trials was included: NSAIDs (n = 4), antidepressants (n = 5), and opioids (n = 8). No studies were found for muscle relaxants; 14 studies had a low risk of bias. The studies only reported effects on the short term (<3 months). The overall quality of the evidence was low. NSAIDs and opioids seem to lead to a somewhat higher relief in pain on the short term, as compared to placebo, in patients with non-specific chronic low back pain; opioids seem to have a small effect in improving function for a selection of patients who responded with an exacerbation of their symptoms after stopping their medication. However, both types of medication show more adverse effects than placebo. There seems to be no difference in effect between antidepressants and placebo in patients with non-specific chronic LBP.     

Coxibs: is there a benefit when compared to traditional non-selective NSAIDs in postoperative pain management?

A multi-modal approach for the management of postoperative pain has become increasingly popular. Strategies to avoid the use of opioids and thus any opioid analgesic related side-effect is an important part of the expansion of ambulatory surgery. Combining long acting local anesthesia in the wound area and non-opioid analgesics are today a basic concept in management of day care, short stay patients. Paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) is often sufficient to provide satisfactory pain relief after minor and intermediate procedures. The use of multimodal or balanced analgesia has since long been shown to facilitate resumption of activities of daily living. The opioid sparing effects of the addition of NSAIDs to morphine patient-controlled analgesic (PCA) after major surgery has also shown repeatedly. The development and introduction of the most selective cyclo-oxygenase-2-inhibitors (Coxibs) was primarily indicated to reduce the risk and severity of gastrointestinal bleeding. The Coxibs have become an interesting option in postoperative pain management. The less pronounced effect on platelet function and subsequent lower risk for impaired hemeostasis makes them, in theory, a preferred option to the non-selective traditional NSAIDs. The benefit versus risk for a more generalized use of Coxibs must, however, be based on a thorough evaluation of the overall benefits and risks for the use of NSAIDs and a further evaluation on whether the specific therapeutic features of the Coxibs provide benefits outweighing their increased cost. This review aims at providing a background and an overview of the benefits versus risks for the use of Coxibs as part of a multimodal postoperative pain management.     

New insights in postoperative pain therapy

In this review, novel clinical studies on postoperative pain therapy are summarized. Based on these studies, several conclusions can be drawn: i) following tonsillectomy, postoperative therapy with NSAIDs leads to a significant increase in the number of reoperations; thus NSAIDs should be used with caution; ii) COX-2 inhibitors in combination with intravenous opioids improve recovery and functional outcome after knee replacement surgery; iii) the combination therapy of different non-opioid analgesics has no proven clinical efficacy and should not be used routinely; iv) patients' age is not a determinant in postoperative opioid titration after surgery; in contrast, it does predict opioid consumption during the first postoperative day; v) morphine and piritramide have identical analgesic efficacy and induce nausea and vomiting with the incidence; opioid selection can, thus, be based on economic considerations and vi) if tramadol is ineffective in postoperative pain therapy, this might be caused by an allelic variant of one of the cytochrome P450 enzymes (CYP2D6); these patients should be treated with a different opioid.     

Psychomotor and cognitive functioning in cancer patients

Psychomotor and cognitive dysfunction in cancer patients can be classified into two main categories according to etiology: disease-induced factors (metabolic disturbances, brain metastasis, pain, etc.) and treatment-related factors (drugs, antineoplastic therapy, etc.). In particular, the effects of chronic opioid administration in cancer patients have been subjected to investigations, and most studies have been engaged in assessment and treatment of the cerebral dysfunction. Early studies found that cancer patients in chronic oral opioid therapy had prolonged continuous reaction times, and that the opioids seemed to be mainly responsible for the prolongation. Significant dose escalations of opioids (≥ 30%) caused transiently impaired psychomotor and cognitive functions in cancer patients. Cancer patients in chronic oral opioid therapy did not achieve any advantages changing to epidural opioid therapy with regard to faster continuous reaction times and less pain.
Large doses of opioids are often required to control severe pain in cancer patients. As increased sedation and impaired psychomotor and cognitive functions often occur, a number of studies have investigated the use of amphetamine derivatives to counteract the sedative side-effects of opioid. These drugs seem promising during high-dose opioid therapy and their use may be particularly rewarding in poor opioid-responsive pain conditions such as incident and neuropathic pain.     

Non-opioid postoperative analgesia

Although significant improvement has been made in the treatment of pain in the postoperative period, many patients still experience unnecessary discomfort resulting in distress, higher morbidity and prolonged stay in hospital. The standard pillar of postoperative treatment of severe pain is the use of opioids. However, adverse reactions to opioids make their use unfavourable. A better understanding of the pathophysiology of pain has helped clinicians to a more balanced approach to postoperative pain treatment. The development of the multimodal approach to postoperative analgesia, with the use of different drugs acting via different routes to give good analgesia, with minimal side-effects, represents a major development in the treatment of postoperative pain. Early, aggressive mobilisation and feeding must follow in order to restore normal conditions quickly. Alternatives to opioids should be used as extensively as possible. Local anaesthesia, used as regional blocks or as wound infiltration, is most beneficial. Paracetamol has good basic analgesic properties, and should probably be used in dosages higher than recommended today. The combination with a NSAID results in better and longer-lasting analgesia. The intravenous form propacetamol will increase the possibilities of its use. The new concept of selective COX-2 inhibiting NSAIDs will result in analgesic and anti-inflammatory drugs with fewer side-effects. The well-known inexpensive group of corticosteroids have good analgesic and anti-emetic properties, and are especially interesting to use in patients who do not tolerate NSAIDs. The alpha2-receptor agonists like clonidine, when administered epidurally or intrathecally, are useful adjuncts, but their adverse effects on sedation and hypotension limit their use. NMDA-receptor antagonists are of limited value in the postoperative period. Adenosine and neostigimine are still on a research level but may lead to new, clinically useful analgesic drugs. In the future, cannabinoids, cholecystokinin-receptor antagonists and neurokinin-1 antagonists may become important analgesic drugs.     

Analgesic agents for the postoperative period. Nonopioids.

For many reasons, nonopioid analgesics have proven to be of immense benefit in postoperative pain relief. Consideration of the limitations and side effects of opioids confirms the need for alternative, complementary analgesics. The current understanding of pain pathophysiology recognizes that many tissue and neuronal factors and changes are invoked by tissue damage, producing peripheral and central sensitization, and some of these may be modulated by the use of NSAIDs, NMDA antagonists, and local anesthetic agents. If successful preemptive analgesic techniques are developed, they will likely include the use of NSAIDs and perhaps NMDA antagonists. Nonopioids are of benefit in multimodal analgesia and allow acute rehabilitation of surgical patients. Acetaminophen, NSAIDs, alpha 2-antagonists, and NMDA antagonists are in routine use as components of multimodal analgesia, in combination with opioids or local anesthetic techniques. Tramadol is interesting because it has nonopioid and opioid actions that can be attributed to the two isomers found in the racemic mixture. Spinal neostigmine and the use of adenosine represent completely different mechanisms of nonopioid analgesia being investigated. Nonopioids, including lidocaine, ketamine, the anticonvulsants, and the antidepressants, are necessary for the treatment of patients with the difficult clinical problem of neuropathic pain that can present in the postoperative period.     

NSAIDs in orthopaedic practice: management guidelines for arthritis patients

Guidelines are provided for prescribing nonsteroidal antiinflammatory drugs (NSAIDs) pre- and postoperatively for arthritis patients. Most NSAIDs impair platelet aggregation and prolong bleeding time, increasing the risk of complications during and immediately following surgery; thus, the effects of individual NSAIDs must be considered prior to surgery. Postoperative treatment issues that must be considered include gastrointestinal safety, renal and hepatic safety, safety in the elderly, and efficacy of various NSAIDs. Various strategies to improve gastrointestinal safety, including use of NSAIDs with low ulcerogenic potential such as nabumetone, low-dose ibuprofen, and etodolac, are discussed. As all NSAIDs can reduce pain and inflammation, selection of a particular NSAID should be based on careful consideration of pharmacologic and clinical differences.     

Nonsteroidal antiinflammatory drugs for postoperative pain management after lumbar spine surgery: a meta-analysis of randomized controlled trials

OBJECT: The authors undertook this meta-analysis to assess the efficacy and safety of nonsteroidal antiinflammatory drugs (NSAIDs) in addition to opioid analgesics on perioperative pain management in lumbar spine surgery. METHODS: The authors searched MEDLINE, Excerpta Medica (EMBASE), The Cochrane Library, CINAHL, PsycINFO, Allied and Complementary Medicine (AMED), and Science Citation Index Expanded databases. In addition, they manually searched key journals and their references. They included randomized trials comparing the use of NSAIDs in addition to opioid analgesics versus opioid analgesics alone after posterior lumbar discectomy, laminectomy, or spinal fusion. Two independent reviewers performed an assessment of the quality of the methods. RESULTS: Seventeen studies comprising 400 patients who received NSAIDs in addition to opioid analgesics and 389 patients receiving opioid analgesics alone were included. Patients receiving NSAIDs in addition to opioid analgesics had lower pain scores and consumed fewer opioids than the group receiving opioid analgesics alone. There was no difference in the incidence of adverse effects. CONCLUSIONS: This meta-analysis provides evidence that the addition of NSAIDs to opioid analgesics in lumbar spine surgery provided better pain control than opioid analgesics alone.