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Cureus Jul 2023Chronic pain is a very common problem in patients with spinal cord injury (SCI) as it affects 80% of these patients, which negatively affects their quality of life.... (Review)
Review
Chronic pain is a very common problem in patients with spinal cord injury (SCI) as it affects 80% of these patients, which negatively affects their quality of life. Despite many advantages that exist in the management of any type of pain (neuropathic, nociceptive, mixed) in these patients, there is no cure, and the analgesic effect of some treatments is inadequate. This study aims to conduct an evidence-based systematic review regarding the various interventions used for the management of pain after SCI. The PubMed, Physiotherapy Evidence Database (PEDro), and Cochrane Library databases were searched from 1969 to 2023. The risk of bias was assessed using the PEDro scoring system. A total of 57 studies met the inclusion criteria and were included in this systematic review. Among the different interventions at present, 18 studies examined the role of oral medications, 11 studies examined the role of minimally invasive methods (injection and infusion), 16 studies investigated physiotherapy and alternative treatments, and 12 studies examined the role of repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and cranial electrotherapy stimulation (CES) in the management of pain in patients after SCI. Gabapentin and pregabalin are very effective in managing chronic neuropathic pain after SCI, and pregabalin also seems to reduce anxiety and sleep disturbances in the patients. It is noteworthy that lamotrigine, valproate, and carbamazepine do not have an analgesic effect, but mirogabalin is a novel and promising drug. Antidepressants (selective serotonin reuptake inhibitors and serotonin and noradrenaline reuptake inhibitors) did not reduce the pain of the patients, although some studies showed an efficacy of amitriptyline especially in depressed patients and tramadol should be considered short-term with caution. Also, tDCS and rTMS reduced pain. Moreover, botulinum toxin type A, lidocaine, ketamine, and intrathecal baclofen significantly reduced pain intensity, although the sample of the studies was small. Physiotherapy and alternative treatments seem to relieve pain, and transcutaneous electrical nerve stimulation had the greatest reduction of pain intensity. In conclusion, several pharmaceutical and non-pharmaceutical methods exist, which can reduce pain in patients after SCI. The type of intervention can be considered by the physician depending on the patients' preference, age, medical history, type of pain, and associated symptoms. However, more studies with greater samples and with better methodological quality should be conducted.
PubMed: 37644939
DOI: 10.7759/cureus.42657 -
International Journal of Molecular... Aug 2023The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical...
The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical development are addressed in this review. A systematic literature search was conducted in three electronic databases (Medline, Web of Science, Scopus) and in the ClinicalTrials.gov register from 1 January 2016 to 1 June 2023 to identify Phase II, III and IV clinical trials evaluating drugs for the treatment of PHN. A total of 18 clinical trials were selected evaluating 15 molecules with pharmacological actions on nine different molecular targets: Angiotensin Type 2 Receptor (AT2R) antagonism (olodanrigan), Voltage-Gated Calcium Channel (VGCC) α2δ subunit inhibition (crisugabalin, mirogabalin and pregabalin), Voltage-Gated Sodium Channel (VGSC) blockade (funapide and lidocaine), Cyclooxygenase-1 (COX-1) inhibition (TRK-700), Adaptor-Associated Kinase 1 (AAK1) inhibition (LX9211), Lanthionine Synthetase C-Like Protein (LANCL) activation (LAT8881), N-Methyl-D-Aspartate (NMDA) receptor antagonism (esketamine), mu opioid receptor agonism (tramadol, oxycodone and hydromorphone) and Nerve Growth Factor (NGF) inhibition (fulranumab). In brief, there are several drugs in advanced clinical development for treating PHN with some of them reporting promising results. AT2R antagonism, AAK1 inhibition, LANCL activation and NGF inhibition are considered first-in-class analgesics. Hopefully, these trials will result in a better clinical management of PHN.
Topics: Humans; Drugs, Investigational; Nerve Growth Factor; Neuralgia, Postherpetic; Pregabalin; Randomized Controlled Trials as Topic
PubMed: 37629168
DOI: 10.3390/ijms241612987 -
European Archives of Psychiatry and... Apr 2024Unspecific symptoms of anxiety and distress are frequently encountered in patients in both general practice and acute psychiatric services. Minor tranquillizers may be a... (Meta-Analysis)
Meta-Analysis
Unspecific symptoms of anxiety and distress are frequently encountered in patients in both general practice and acute psychiatric services. Minor tranquillizers may be a treatment option when non-pharmacological interventions are insufficient or unavailable. We conducted a systematic review with network meta-analysis of the evidence for short-term (1-4 weeks) pharmacological treatment of newly onset symptoms of anxiety and distress. We searched the PsycInfo, MEDLINE, EMBASE and Cochrane Library databases and extracted data following a predefined hierarchy of outcomes. We assessed risk of bias using the Cochrane Risk of Bias tool and the certainty of the evidence using the Grading of Recommendations Assessment, Development and Evaluation framework (GRADE). We included 34 randomized trials comprising a total of 7044 patients with adjustment disorders or anxiety spectrum disorders. The network meta-analysis showed that regarding the critical outcome symptoms of anxiety within 1-4 weeks benzodiazepines (SMD - 0.58, 95% CI - 0.77 to - 0.40), quetiapine (SMD - 0.51, 95% CI - 0.90 to - 0.13) and pregabalin (SMD - 0.58, 95% CI - 0.87 to - 0.28) all performed better than placebo with no statistically significant difference between the drugs. Data on other important outcomes were inconsistently reported. Adverse effects varied, but overall, it was uncertain whether adverse effects differed between interventions. The evidence regarding the risk of dependence was uncertain, but dependence may be a concern in susceptible individuals even with short-term treatment. Overall, the certainty of the evidence according to GRADE was rated as low to very low across outcomes. Despite the limitations in the evidence, the results of this review can inform treatment guidelines, supporting clinicians in the choice of minor tranquillizer in this prevalent and help-seeking, clinically heterogeneous population.
Topics: Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic; Anxiety; Anxiety Disorders; Anti-Anxiety Agents
PubMed: 37624378
DOI: 10.1007/s00406-023-01680-0 -
Journal of Clinical Medicine Jul 2023(1) Background: Pain after a burn injury is difficult to endure, and emerging studies aim to ascertain the effects of gabapentin and pregabalin as non-opioid treatment... (Review)
Review
(1) Background: Pain after a burn injury is difficult to endure, and emerging studies aim to ascertain the effects of gabapentin and pregabalin as non-opioid treatment options. (2) Methods: We searched for randomised controlled trials (RCTs) in six databases. The risk of bias was assessed using the RoB 2.0 tool. We performed meta-analysis and trial sequential analysis and used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology for judging the certainty of evidence (CoE). (3) Results: Five RCTs were included. Compared with placebo, gabapentinoids significantly decreased the pain intensity within 24 h (mean difference (MD) = -1.06, 95% confidence interval (CI): -1.47--0.65) and from 72 h to 9 days (MD = -0.82, 95% CI: -1.16--0.48), but not after 3 weeks (MD = -0.44, 95% CI: -1.31-0.42). Opioid consumption (mg/day) was reduced within 24 h (MD = -13.34, 95% CI: -22.16--4.52) and from 72 h to 9 days (MD = -7.87, 95% CI: -14.82--0.91). Increased risks of drowsiness (risk ratio (RR) = 3.255, 95% CI: 1.135-9.335) and dizziness (RR = 3.034, 95% CI: 1.006-9.147) were observed, but sensitivity analysis using the Bayesian method showed no increased risk. All endpoints were judged as low to very low CoE. (4) Conclusions: Gabapentinoids offer modest analgesic benefits as a component of multimodal pain management for burn injuries of less than 3 weeks. The adverse effects should be carefully monitored. Large-scale RCTs are warranted for the reinforcement of CoE in clinical use.
PubMed: 37568444
DOI: 10.3390/jcm12155042 -
JAMA Network Open Aug 2023Patients undergoing spine surgery often experience severe pain. The optimal dosage of pregabalin and gabapentin for pain control and safety in these patients has not... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Patients undergoing spine surgery often experience severe pain. The optimal dosage of pregabalin and gabapentin for pain control and safety in these patients has not been well established.
OBJECTIVE
To evaluate the associations of pain, opioid consumption, and adverse events with different dosages of pregabalin and gabapentin in patients undergoing spine surgery.
DATA SOURCES
PubMed/MEDLINE, Embase, Web of Science, Cochrane library, and Scopus databases were searched for articles until August 7, 2021.
STUDY SELECTION
Randomized clinical trials conducted among patients who received pregabalin or gabapentin while undergoing spine surgery were included.
DATA EXTRACTION AND SYNTHESIS
Two investigators independently performed data extraction following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) reporting guideline. The network meta-analysis was conducted from August 2022 to February 2023 using a random-effects model.
MAIN OUTCOMES AND MEASURES
The primary outcome was pain intensity measured using the Visual Analog Scale (VAS), and secondary outcomes included opioid consumption and adverse events.
RESULTS
Twenty-seven randomized clinical trials with 1861 patients (median age, 45.99 years [range, 20.00-70.00 years]; 759 women [40.8%]) were included in the systematic review and network meta-analysis. Compared with placebo, the VAS pain score was lowest with gabapentin 900 mg per day, followed by gabapentin 1200 mg per day, gabapentin 600 mg per day, gabapentin 300 mg per day, pregabalin 300 mg per day, pregabalin 150 mg per day, and pregabalin 75 mg per day. Additionally, gabapentin 900 mg per day was found to be associated with the lowest opioid consumption among all dosages of gabapentin and pregabalin, with a mean difference of -22.07% (95% CI, -33.22% to -10.92%) for the surface under the cumulative ranking curve compared with placebo. There was no statistically significant difference in adverse events (nausea, vomiting, and dizziness) among all treatments. No substantial inconsistency between direct and indirect evidence was detected for all outcomes.
CONCLUSIONS AND RELEVANCE
These findings suggest that gabapentin 900 mg per day before spine surgery is associated with the lowest VAS pain score among all dosages. In addition, no differences in adverse events were noted among all treatments.
Topics: Humans; Female; Middle Aged; Gabapentin; Pregabalin; Analgesics; Analgesics, Opioid; Network Meta-Analysis; Pain, Postoperative
PubMed: 37556139
DOI: 10.1001/jamanetworkopen.2023.28121 -
British Journal of Pain Aug 2023Despite the enormous success of anterior cruciate ligament (ACL) reconstruction, acute neuropathic pain can develop postoperatively and is both distressing and difficult...
BACKGROUND
Despite the enormous success of anterior cruciate ligament (ACL) reconstruction, acute neuropathic pain can develop postoperatively and is both distressing and difficult to treat once established. Pregabalin, an anticonvulsant agent that selectively affects the nociceptive process, has been used as a pain relief agent. The purpose of this systematic review of randomized controlled trials (RCTs) was to evaluate the pain control effect of pregabalin versus placebo after ACL reconstruction.
METHOD
A search of the literature was performed from inception to June 2022, using PubMed, Scopus, Google Scholar, Web of Science, Cochrane and EBSCO. Studies considered for inclusion were RCTs that reported relevant outcomes (postoperative pain scores, cumulative opioid consumption, adverse events) following administration of pregabalin in patients undergoing ACL reconstruction.
RESULT
Five placebo-controlled RCTs involving 272 participants met the inclusion criteria. 75 mg and 150 mg oral pregabalin was used in included trials. Two studies used a single dose of pregabalin one hour before anesthesia induction. Two studies used pregabalin 1 hour before anesthesia induction and 12 hours after. One study used daily pregabalin 7 days before and 7 days after surgery. Out of five papers, three papers found significantly lower pain intensity and cumulative opioid consumption in pregabalin group compared with placebo group. However, a decrease in pain scores was found in all trials. Pregabalin administration was associated with dizziness and nausea.
CONCLUSION
The use of pregabalin may be a valuable asset in pain management after ACL reconstruction. However, future studies with larger sample size and longer follow-up period are required.
PubMed: 37538943
DOI: 10.1177/20494637231152967 -
European Spine Journal : Official... Sep 2023The aim of the present systematic review was to investigate the effectiveness of pharmacological and non-pharmacological therapy on pain intensity and disability in... (Meta-Analysis)
Meta-Analysis Review
Effectiveness of pharmacological and non-pharmacological therapy on pain intensity and disability in older people with chronic nonspecific low back pain: a systematic review with meta-analysis.
BACKGROUND AND PURPOSE
The aim of the present systematic review was to investigate the effectiveness of pharmacological and non-pharmacological therapy on pain intensity and disability in older people with chronic nonspecific low back pain.
METHODS
Searches were conducted in the MEDLINE, COCHRANE LIBRARY, EMBASE, AMED, PSYCINFO, and PEDRO databases up to 2022. Risk of bias was appraised using the Cochrane Risk of Bias 2.0 tool. Estimated mean differences and respective 95% confidence intervals were presented for each paired comparison and the strength of the current evidence was assessed using the GRADE approach.
RESULTS AND DISCUSSION
Thirty-one original trials involving 2120 participants were included. All outcomes were self-rated. Pain intensity was measured using the Visual Analogue Scale or Numerical Rating Scale. Disability was evaluated using the Roland Morris Disability Questionnaire, Oswestry Disability Index or Hannover Functional Ability Questionnaire. Short-term: Moderate quality of evidence that mindfulness reduces disability compared to patient education (mean difference [MD] = - 1.38 [95% CI - 2.02 to - 0.73]); low-quality evidence that mixed exercise (MD = - 50.33 [95% CI - 57.11 to - 43.56]) reduces pain compared to no intervention, waiting list, placebo or sham; low quality of evidence that there is no effect for opioid compared to placebo (MD = - 8.26 [95% CI - 19.29 to 2.77]) with regards to reducing pain and opioid/acetaminophen reduces disability more compared to pregabalin (MD = 2.36 [95% CI] 1.86-2.86]).
CONCLUSIONS
The findings showed low or very low quality of evidence for non-pharmacological interventions with a large effect in short- and long-term follow-up. The two studies that provided moderate quality of evidence had a small clinical effect. Only two studies were found that investigated pharmacological therapies-both with low quality of evidence. However, the studies were methodologically weak and had small sample sizes. Given the adverse effects of low back pain and the scarce information on the effectiveness of pharmacological and non-pharmacological treatments for older people, future randomized trials should be encouraged.
Topics: Humans; Aged; Low Back Pain; Pain Measurement; Analgesics, Opioid; Exercise; Exercise Therapy; Chronic Pain
PubMed: 37464184
DOI: 10.1007/s00586-023-07857-4 -
The Journal of Spinal Cord Medicine Jul 2024Neuropathic pain is a common and debilitating condition following SCI. While treatments for neuropathic pain intensity have been reviewed, the impact on pain... (Review)
Review
CONTEXT
Neuropathic pain is a common and debilitating condition following SCI. While treatments for neuropathic pain intensity have been reviewed, the impact on pain interference has not been summarized.
OBJECTIVE
To systematically review the effect of neuropathic pain interventions on pain interference in individuals with spinal cord injury.
METHODS
This systematic review included randomized controlled trials and quasi-experimental (non-randomized) studies which assessed the impact of an intervention on pain interference in individuals with spinal cord injury and neuropathic pain. Articles were identified by searching MEDLINE (1996 to April 11, 2022), EMBASE (1996 to April 11, 2022), PsycInfo (1987 to April, week 2, 2022). Studies were assessed for methodologic quality using a modified GRADE approach and were given quality of evidence (QOE) scores on a 4-point scale ranging from very low to high.
RESULTS
Twenty studies met the inclusion criteria. These studies fell into the following categories: anticonvulsants ( = 2), antidepressants ( = 1), analgesics ( = 1), antispasmodics ( = 1), acupuncture ( = 2), transcranial direct current stimulation ( = 1), active cranial electrotherapy stimulation ( = 2), transcutaneous electrical nerve stimulation ( = 2), repetitive transcranial magnetic stimulation ( = 1), functional electrical stimulation ( = 1), meditation and imagery ( = 1), self-hypnosis and biofeedback ( = 1), and interdisciplinary pain programs ( = 4).
CONCLUSION
When considering studies of moderate to high quality, pregabalin, gabapentin, intrathecal baclofen, transcranial direct current stimulation, and transcutaneous electrical nerve stimulation (in 1 of 2 studies) were shown to have beneficial effects on pain interference. However, due to the low number of high-quality studies further research is required to confirm the efficacy of these interventions prior to recommending their use to reduce pain interference.
Topics: Humans; Spinal Cord Injuries; Neuralgia; Pain Management; Analgesics
PubMed: 37428448
DOI: 10.1080/10790268.2023.2218186 -
The Journal of Urology Nov 2023Ureteral stents are commonly used for the treatment of ureteral obstruction, most often urolithiasis. Their use may be associated with significant bothersome symptoms... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Ureteral stents are commonly used for the treatment of ureteral obstruction, most often urolithiasis. Their use may be associated with significant bothersome symptoms and discomfort. Prior studies have examined the effects of various medication regimens on ureteral stent symptoms. This study utilized Bayesian network meta-analysis to analyze all available evidence on the pharmacological management of ureteral stent-related symptoms.
MATERIALS AND METHODS
In December 2022 a systematic review was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines on randomized prospective studies on pharmacological management of ureteral stent-related symptoms reporting outcomes using the Ureteral Stent Symptom Questionnaire score on urinary symptoms and pain. The data were analyzed in Review Manager 5.3 and R Studio where a Bayesian network meta-analysis was performed. Treatments were ranked using surface under the cumulative ranking curve and mean difference vs placebo with 95% credible intervals.
RESULTS
A total of 26 studies were analyzed. These were used to build networks which were modeled to run 100,000 Markov Chain Montecarlo simulations each. Drug-class analysis revealed the most effective class for each domain: for urinary symptoms, sexual performance, general health, and work performance-combined α-blocker and anticholinergic and phosphodiesterase 5 inhibitors; for pain-combined anticholinergic and pregabalin. The following were the most effective drugs and dosages for specific symptoms: for urinary symptoms-combined silodosin 8 mg+solifenacin 10 mg; for pain-combined silodosin 8 mg+solifenacin 10 mg; for sexual performance-tadalafil 5 mg. Combined silodosin 8 mg+solifenacin 10 mg+tadalafil 5 mg has the best general health scores while solifenacin 10 mg had the best work experience scores.
CONCLUSIONS
This network meta-analysis demonstrated that the most effective drug therapy is different for each symptom domain. It is important to consider a patient's chief complaint and domains in order to ascertain the optimal medication regimen for each patient. Further iterations of this analysis can be strengthened by trials that directly compare more of these drugs instead of relying on indirect evidence.
Topics: Humans; Solifenacin Succinate; Tadalafil; Network Meta-Analysis; Prospective Studies; Bayes Theorem; Quality of Life; Ureter; Pain; Cholinergic Antagonists; Stents
PubMed: 37428119
DOI: 10.1097/JU.0000000000003616