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British Journal of Anaesthesia Jun 2014Opioids can increase sensitivity to noxious stimuli and cause opioid-induced hyperalgesia. We performed a systematic review to evaluate the clinical consequences of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Opioids can increase sensitivity to noxious stimuli and cause opioid-induced hyperalgesia. We performed a systematic review to evaluate the clinical consequences of intra-operative doses of opioid.
METHODS
We identified randomized controlled trials which compared intra-operative opioid to lower doses or placebo in adult patients undergoing surgery from MEDLINE, EMBASE, LILAC, Cochrane, and hand searches of trial registries. We pooled data of postoperative pain intensity, morphine consumption, incidence of opioid-related side-effects, primary and secondary hyperalgesia. For dichotomous outcomes relative risks [95% confidence intervals (CIs)] and for continuous outcomes mean differences (MDs) or standardized mean difference (SMD; 95% CI) were calculated.
RESULTS
Twenty-seven studies involving 1494 patients were included in the analysis. Patients treated with high intra-operative doses of opioid reported higher postoperative pain intensity than the reference groups (MD: 9.4 cm; 95% CI: 4.4, 14.5) at 1 h, (MD: 7.1 cm; 95% CI: 2.8, 11.3) at 4 h, and (MD: 3 cm; 95% CI: 0.4, 5.6) at 24 h on a 100 cm visual analogue scale. They also showed higher postoperative morphine use after 24 h (SMD: 0.7; 95% CI: 0.37, 1.02). There was no difference in the incidences of nausea, vomiting, and drowsiness. These results were mainly associated with the use of remifentanil. The impact of other opioids is less clear because of limited data.
DISCUSSION
This review suggests that high intra-operative doses of remifentanil are associated with small but significant increases in acute pain after surgery.
Topics: Analgesics, Opioid; Dose-Response Relationship, Drug; Humans; Hyperalgesia; Pain Measurement; Pain, Postoperative; Piperidines; Randomized Controlled Trials as Topic; Remifentanil
PubMed: 24829420
DOI: 10.1093/bja/aeu137 -
The Cochrane Database of Systematic... Apr 2014Iatrogenic injury of the inferior alveolar or lingual nerve or both is a known complication of oral and maxillofacial surgery procedures. Injury to these two branches of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Iatrogenic injury of the inferior alveolar or lingual nerve or both is a known complication of oral and maxillofacial surgery procedures. Injury to these two branches of the mandibular division of the trigeminal nerve may result in altered sensation associated with the ipsilateral lower lip or tongue or both and may include anaesthesia, paraesthesia, dysaesthesia, hyperalgesia, allodynia, hypoaesthesia and hyperaesthesia. Injury to the lingual nerve may also affect taste perception on the affected side of the tongue. The vast majority (approximately 90%) of these injuries are temporary in nature and resolve within eight weeks. However, if the injury persists beyond six months it is deemed to be permanent. Surgical, medical and psychological techniques have been used as a treatment for such injuries, though at present there is no consensus on the preferred intervention, or the timing of the intervention.
OBJECTIVES
To evaluate the effects of different interventions and timings of interventions to treat iatrogenic injury of the inferior alveolar or lingual nerves.
SEARCH METHODS
We searched the following electronic databases: the Cochrane Oral Health Group's Trial Register (to 9 October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 9), MEDLINE via OVID (1946 to 9 October 2013) and EMBASE via OVID (1980 to 9 October 2013). No language restrictions were placed on the language or date of publication when searching the electronic databases.
SELECTION CRITERIA
Randomised controlled trials (RCTs) involving interventions to treat patients with neurosensory defect of the inferior alveolar or lingual nerve or both as a sequela of iatrogenic injury.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by The Cochrane Collaboration. We performed data extraction and assessment of the risk of bias independently and in duplicate. We contacted authors to clarify the inclusion criteria of the studies.
MAIN RESULTS
Two studies assessed as at high risk of bias, reporting data from 26 analysed participants were included in this review. The age range of participants was from 17 to 55 years. Both trials investigated the effectiveness of low-level laser treatment compared to placebo laser therapy on inferior alveolar sensory deficit as a result of iatrogenic injury.Patient-reported altered sensation was partially reported in one study and fully reported in another. Following treatment with laser therapy, there was some evidence of an improvement in the subjective assessment of neurosensory deficit in the lip and chin areas compared to placebo, though the estimates were imprecise: a difference in mean change in neurosensory deficit of the chin of 8.40 cm (95% confidence interval (CI) 3.67 to 13.13) and a difference in mean change in neurosensory deficit of the lip of 21.79 cm (95% CI 5.29 to 38.29). The overall quality of the evidence for this outcome was very low; the outcome data were fully reported in one small study of 13 patients, with differential drop-out in the control group, and patients suffered only partial loss of sensation. No studies reported on the effects of the intervention on the remaining primary outcomes of pain, difficulty eating or speaking or taste. No studies reported on quality of life or adverse events.The overall quality of the evidence was very low as a result of limitations in the conduct and reporting of the studies, indirectness of the evidence and the imprecision of the results.
AUTHORS' CONCLUSIONS
There is clearly a need for randomised controlled clinical trials to investigate the effectiveness of surgical, medical and psychological interventions for iatrogenic inferior alveolar and lingual nerve injuries. Primary outcomes of this research should include: patient-focused morbidity measures including altered sensation and pain, pain, quantitative sensory testing and the effects of delayed treatment.
Topics: Humans; Iatrogenic Disease; Lingual Nerve Injuries; Low-Level Light Therapy; Randomized Controlled Trials as Topic; Somatosensory Disorders; Time Factors; Trigeminal Nerve Injuries
PubMed: 24740534
DOI: 10.1002/14651858.CD005293.pub2 -
The Cochrane Database of Systematic... Oct 2013This is an update of the original Cochrane review published in Issue 2, 2007. The cause of postherpetic neuralgia is damage to peripheral neurons, dorsal root ganglia,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an update of the original Cochrane review published in Issue 2, 2007. The cause of postherpetic neuralgia is damage to peripheral neurons, dorsal root ganglia, and the dorsal horn of the spinal cord, secondary to herpes zoster infection (shingles). In postherpetic neuralgia, peripheral neurons discharge spontaneously and have lowered activation thresholds, and exhibit an exaggerated response to stimuli. Topical lidocaine dampens peripheral nociceptor sensitisation and central nervous system hyperexcitability, and may benefit patients with postherpetic neuralgia.
OBJECTIVES
To examine efficacy and safety of topical lidocaine in the treatment of postherpetic neuralgia.
SEARCH METHODS
We searched the Cochrane Pain, Palliative and Supportive Care Group Trials Register, CENTRAL, MEDLINE, EMBASE, LILACS, SIGLE, Citation Index, the reference lists of all eligible trials, key textbooks, and previous systematic reviews. Last search conducted April 2011.
SELECTION CRITERIA
Randomised or quasi‐randomised trials comparing topical applications of lidocaine in patients of all ages with postherpetic neuralgia (pain persisting at the site of shingles at least one month after the onset of the acute rash).
DATA COLLECTION AND ANALYSIS
Two review authors extracted data, and a third checked them.
MAIN RESULTS
In the original review three studies involving 182 topical lidocaine treated participants and 132 control participants were included. Two studies gave data on pain relief, and the remaining study provided data on secondary outcome measures. The largest study published as an abstract compared topical lidocaine patch to a placebo patch and accounted for 150 of the 314 participants (48%). A meta‐analysis combining two studies identified a significant difference between topical lidocaine and control groups for the primary outcome measure: a mean improvement in pain relief according to a pain relief scale. Topical lidocaine relieved pain better than placebo (P = 0.003). There was a statistical difference between the groups for the secondary outcome measure of mean VAS score reduction (P = 0.03), but this was only for a single small study. There were a similar number of adverse skin reactions in both treatment and placebo groups. The highest recorded blood lidocaine concentration varied between 59 ng/ml and 431 ng/ml between studies. The latter figure is high and the authors of the study suggest that the sample had been contaminated during the assay procedure.
AUTHORS' CONCLUSIONS
Since the last version of this review in Issue 2, 2007 no new studies have been found and the results therefore remain the same. There is still insufficient evidence to recommend topical lidocaine as a first‐line agent in the treatment of postherpetic neuralgia with allodynia. Further research should be undertaken on the efficacy of topical lidocaine for other chronic neuropathic pain disorders, and also to compare different classes of drugs (e.g. topical anaesthetic applications versus anti‐epileptic drugs).
Topics: Administration, Topical; Anesthetics, Local; Humans; Lidocaine; Neuralgia, Postherpetic
PubMed: 24166584
DOI: 10.1002/14651858.CD004846.pub3 -
The Cochrane Database of Systematic... Aug 2013The use of opioids in the long-term management of chronic low-back pain (CLBP) has increased dramatically. Despite this trend, the benefits and risks of these... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The use of opioids in the long-term management of chronic low-back pain (CLBP) has increased dramatically. Despite this trend, the benefits and risks of these medications remain unclear. This review is an update of a Cochrane review first published in 2007.
OBJECTIVES
To determine the efficacy of opioids in adults with CLBP.
SEARCH METHODS
We electronically searched the Cochrane Back Review Group's Specialized Register, CENTRAL, CINAHL and PsycINFO, MEDLINE, and EMBASE from January 2006 to October 2012. We checked the reference lists of these trials and other relevant systematic reviews for potential trials for inclusion.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) that assessed the use of opioids (as monotherapy or in combination with other therapies) in adults with CLBP that were at least four weeks in duration. We included trials that compared non-injectable opioids to placebo or other treatments. We excluded trials that compared different opioids only.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed the risk of bias and extracted data onto a pre-designed form. We pooled results using Review Manager (RevMan) 5.2. We reported on pain and function outcomes using standardized mean difference (SMD) or risk ratios with 95% confidence intervals (95% CI). We used absolute risk difference (RD) with 95% CI to report adverse effects.
MAIN RESULTS
We included 15 trials (5540 participants). Tramadol was examined in five trials (1378 participants); it was found to be better than placebo for pain (SMD -0.55, 95% CI -0.66 to -0.44; low quality evidence) and function (SMD -0.18, 95% CI -0.29 to -0.07; moderate quality evidence). Transdermal buprenorphine (two trials, 653 participants) may make little difference for pain (SMD -2.47, 95%CI -2.69 to -2.25; very low quality evidence), but no difference compared to placebo for function (SMD -0.14, 95%CI -0.53 to 0.25; very low quality evidence). Strong opioids (morphine, hydromorphone, oxycodone, oxymorphone, and tapentadol), examined in six trials (1887 participants), were better than placebo for pain (SMD -0.43, 95%CI -0.52 to -0.33; moderate quality evidence) and function (SMD -0.26, 95% CI -0.37 to -0.15; moderate quality evidence). One trial (1583 participants) demonstrated that tramadol may make little difference compared to celecoxib (RR 0.82, 95% CI 0.76 to 0.90; very low quality evidence) for pain relief. Two trials (272 participants) found no difference between opioids and antidepressants for either pain (SMD 0.21, 95% CI -0.03 to 0.45; very low quality evidence), or function (SMD -0.11, 95% -0.63 to 0.42; very low quality evidence). The included trials in this review had high drop-out rates, were of short duration, and had limited interpretability of functional improvement. They did not report any serious adverse effects, risks (addiction or overdose), or complications (sleep apnea, opioid-induced hyperalgesia, hypogonadism). In general, the effect sizes were medium for pain and small for function.
AUTHORS' CONCLUSIONS
There is some evidence (very low to moderate quality) for short-term efficacy (for both pain and function) of opioids to treat CLBP compared to placebo. The very few trials that compared opioids to non-steroidal anti-inflammatory drugs (NSAIDs) or antidepressants did not show any differences regarding pain and function. The initiation of a trial of opioids for long-term management should be done with extreme caution, especially after a comprehensive assessment of potential risks. There are no placebo-RCTs supporting the effectiveness and safety of long-term opioid therapy for treatment of CLBP.
Topics: Adult; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Chronic Pain; Female; Humans; Low Back Pain; Male; Middle Aged; Randomized Controlled Trials as Topic
PubMed: 23983011
DOI: 10.1002/14651858.CD004959.pub4 -
Pain Physician 2013Chronic pelvic pain (CPP) is a complex pain syndrome. Since its pathogenesis is still poorly understood and structural alterations in pain related brain regions may be... (Review)
Review
BACKGROUND
Chronic pelvic pain (CPP) is a complex pain syndrome. Since its pathogenesis is still poorly understood and structural alterations in pain related brain regions may be present, there is a greater acceptance that sensitization of the central nervous system (CNS) plays an important role in the development and maintenance of chronicity.
OBJECTIVE
The purpose of this study is to systematically review the scientific evidence regarding central sensitization (CS) in female patients with urogynecological CPP.
STUDY DESIGN
Systematic review of the literature.
METHODS
A systematic literature search was conducted in PubMed and Web of Science using different keyword combinations related to urogynecological CPP and central sensitization. Full text clinical reports addressing CS in adult women with urogynecological CPP were included and assessed for methodological quality by 2 independent reviewers.
RESULTS
After screening for the eligibility, a total of 29 full-text articles with low to good methodological quality were retained. All studies were observational, 27 of which were case-control and 2 of which were cohorts. Sensitivity of the CNS was investigated by using a variety of methods. Although different central mechanisms seem to be involved in pain processing, the present evidence suggests hyperexcitability of the CNS in patients with urogynecological CPP. Altered brain morphology and function, generalized hyperalgesia to different type of stimuli, overactive bottom-up nociceptive mechanisms, and autonomic dysregulation were established in patients with urogynecological CPP. Nevertheless, diffuse noxious inhibitory control seemed normal, and therefore the contribution of an impaired endogenous pain inhibition mechanism to CPP requires further study. The same goes for the contribution of psychological factors.
LIMITATIONS
The level of evidence of retained studies is low due to the observational study designs and a wide range of diagnoses and assessment methods.
CONCLUSION
Although the majority of the literature provides evidence for the presence of CS in urogynecological CPP with changes in brain morphology/function and sensory function, it is unclear whether these changes in central pain processing are secondary or primary to CPP, especially since evidence regarding the function of endogenous pain inhibition and the role of psychosocial pain facilitation is scarce. Further studies with good methodological quality are needed in order to clarify exact mechanisms.
Topics: Central Nervous System Sensitization; Chronic Pain; Female; Humans; Hyperalgesia; Pelvic Pain; Research Design; Treatment Outcome
PubMed: 23877446
DOI: No ID Found -
Anesthesiology Jun 2012Systemic α2 agonists are believed to reduce pain and opioid requirements after surgery, thus decreasing the incidence of opioid-related adverse effects, including... (Meta-Analysis)
Meta-Analysis Review
Effect of perioperative systemic α2 agonists on postoperative morphine consumption and pain intensity: systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Systemic α2 agonists are believed to reduce pain and opioid requirements after surgery, thus decreasing the incidence of opioid-related adverse effects, including hyperalgesia.
METHODS
The authors searched for randomized placebo-controlled trials testing systemic α2 agonists administrated in surgical patients and reporting on postoperative cumulative opioid consumption and/or pain intensity. Meta-analyses were performed when data from 5 or more trials and/or 100 or more patients could be combined.
RESULTS
Thirty studies (1,792 patients, 933 received clonidine or dexmedetomidine) were included. There was evidence of postoperative morphine-sparing at 24 h; the weighted mean difference was -4.1 mg (95% confidence interval, -6.0 to -2.2) with clonidine and -14.5 mg (-22.1 to -6.8) with dexmedetomidine. There was also evidence of a decrease in pain intensity at 24 h; the weighted mean difference was -0.7 cm (-1.2 to -0.1) on a 10-cm visual analog scale with clonidine and -0.6 cm (-0.9 to -0.2) with dexmedetomidine. The incidence of early nausea was decreased with both (number needed to treat, approximately nine). Clonidine increased the risk of intraoperative (number needed to harm, approximately nine) and postoperative hypotension (number needed to harm, 20). Dexmedetomidine increased the risk of postoperative bradycardia (number needed to harm, three). Recovery times were not prolonged. No trial reported on chronic pain or hyperalgesia.
CONCLUSIONS
Perioperative systemic α2 agonists decrease postoperative opioid consumption, pain intensity, and nausea. Recovery times are not prolonged. Common adverse effects are bradycardia and arterial hypotension. The impact of α2 agonists on chronic pain or hyperalgesia remains unclear because valid data are lacking.
Topics: Adrenergic alpha-2 Receptor Agonists; Analgesics, Opioid; Anesthesia Recovery Period; Clonidine; Dexmedetomidine; Hemodynamics; Humans; Hyperalgesia; Hypotension; Morphine; Pain Measurement; Pain, Postoperative; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic
PubMed: 22546966
DOI: 10.1097/ALN.0b013e31825681cb -
Annals of Physical and Rehabilitation... Mar 2009The pharmacological treatment of patients with spinal cord injury (SCI) pain remains challenging despite new available drugs. Such treatment should always be viewed in...
Chronic neuropathic pain management in spinal cord injury patients. What is the efficacy of pharmacological treatments with a general mode of administration? (oral, transdermal, intravenous).
INTRODUCTION
The pharmacological treatment of patients with spinal cord injury (SCI) pain remains challenging despite new available drugs. Such treatment should always be viewed in the context of global pain management in these patients. To date few clinical trials have been specifically devoted to this topic, and the implementation of treatments is generally based on results obtained in peripheral neuropathic pain. The aim of this review is to present evidence for efficacy and tolerability of pharmacological treatments in SCI pain and propose therapeutic recommendations.
MATERIAL AND METHODS
The methodology follows the guidelines of the French Society of Physical Medicine and Rehabilitation (SOFMER). It includes a systematic review of the litterature which is performed by two independent experts. The selected studies are analysed and classified into four levels of evidence (1 to 4) and three grades of recommendations are proposed (A, B, C). The review is further validated by a reading committee.
RESULTS
The efficacy of pregabalin has been confirmed in neuropathic pain associated with SCI (grade A). Gabapentin has a lower level of evidence in SCI pain (grade B) but a grade A level of evidence for efficacy in peripheral neuropathic pain. Both drugs can be proposed as first line therapy and are safe to use. Tricyclic antidepressants (TCAs) can also be proposed first line (grade B for SCI pain associated with depression, grade A for other neuropathic pain conditions), especially in patients with comorbid depressive symptoms. Tramadol can be proposed alone or in combination with antiepileptic drugs if the pain has a predominant non-neuropathic component. If these treatments fail, strong opioids can be proposed as second/third line (grade B in SCI, grade A in other types of neuropathic pain). Lamotrigine may also be proposed at this stage, particularly in patients with incomplete SCI associated with allodynia (grade B). In refractory central pain, cannabinoids may be proposed on the basis of positive results in other central pain conditions (e.g. multiple sclerosis). Intravenous ketamine and lidocaine can only be proposed in specialized centers. Drug combinations may be envisaged in case of partial response to first or second line therapy.
CONCLUSIONS
Very few pharmacological studies have dealt specifically with neuropathic pain related to SCI. Large scale studies and trials comparing several active drugs are warranted in SCI pain.
Topics: Algorithms; Analgesics, Opioid; Anesthetics, Local; Anticonvulsants; Antidepressive Agents; Chronic Disease; Humans; Neuralgia; Spinal Cord Injuries
PubMed: 19909703
DOI: 10.1016/j.rehab.2008.12.011 -
Anesthesiology Mar 2006Opioids are the cornerstone therapy for the treatment of moderate to severe pain. Although common concerns regarding the use of opioids include the potential for... (Review)
Review
Opioids are the cornerstone therapy for the treatment of moderate to severe pain. Although common concerns regarding the use of opioids include the potential for detrimental side effects, physical dependence, and addiction, accumulating evidence suggests that opioids may yet cause another problem, often referred to as opioid-induced hyperalgesia. Somewhat paradoxically, opioid therapy aiming at alleviating pain may render patients more sensitive to pain and potentially may aggravate their preexisting pain. This review provides a comprehensive summary of basic and clinical research concerning opioid-induced hyperalgesia, suggests a framework for organizing pertinent information, delineates the status quo of our knowledge, identifies potential clinical implications, and discusses future research directions.
Topics: Analgesics, Opioid; Animals; Humans; Hyperalgesia; Opioid-Related Disorders
PubMed: 16508405
DOI: 10.1097/00000542-200603000-00025