Neuropathic pain phenotyping as a predictor of treatment response in painful diabetic neuropathy: Data from the randomized, double-blind, COMBO-DN study

Bouhassira, Didier; Wilhelm, Stefan; Schacht, Alexander; Perrot, Serge; Kosek, Eva; Cruccu, G.; Freynhagen, Rainer; Tesfaye, Solomon; Lledó, Alberto; Choy, Ernest; Marchettini, Paolo; Micó, Juan Antonio; Spaeth, M. J. Drake; Skljarevski, Vladimir; Tölle, Thomas R.

doi:10.1016/j.pain.2014.08.020

Cited by 118 publications

(95 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…55–57 Interestingly, the results of a number of very recent trials or posthoc analyses of recent trials suggest that some drugs might be differentially effective in patients classified based on their sensory phenotypes. 58–60 …”

Section: Discussionmentioning

confidence: 99%

Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis

Finnerup

Attal

Haroutounian

et al. 2015

The Lancet Neurology

3,086

2,119

View full text Add to dashboard Cite

Summary Background Neuropathic pain is difficult to treat. New treatments, clinical trials and standards of quality for assessing evidence justify an update of evidence-based recommendations for its pharmacological treatment. Methods The Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain conducted a systematic review of randomised double-blind studies of oral and topical pharmacotherapy for neuropathic pain, including unpublished trials (retrieved from clinicaltrials.gov and pharmaceutical websites). Meta-analysis used Numbers Needed to Treat (NNT) for 50 % pain relief as primary measure and assessed publication bias. Recommendations used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Findings In total 229 studies were included. Analysis of publication bias suggested a 10% overstatement of treatment effects. Studies published in peer-review journals reported greater effects than online studies (R2=9·3%, p<0·01). Trial outcomes were generally modest even for effective drugs : in particular NNTs were 3·6 (95 % CI 3·0–4·4) for tricyclic antidepressants (TCAs), 6·4 (95 % CI 5·2–8·4) for serotonin- noradrenaline reuptake inbibitor (SNRI) antidepressants duloxetine and venlafaxine, 7·7 (95 % CI 6·5–9·4) for pregabalin and 6·3 (95 % CI 5·0–8·3) for gabapentin. NNTs were higher for gabapentin ER/enacarbil and capsaicin high concentration patches, lower for opioids and botulinum toxin A (BTX-A) and undetermined for lidocaine patches. Final quality of evidence was lower for lidocaine patches and BTX-A. Tolerability/safety and values/preferences were high for lidocaine patches and lower for opioids and TCAs. This permitted a strong GRADE recommendation for use and proposal as first line for TCAs, SNRIs, pregabalin, gabapentin and gabapentin ER/enacarbil in neuropathic pain, a weak recommendation for use and proposal as second line for lidocaine patches, capsaicin patches and tramadol, and a weak recommendations for use and proposal as third line for strong opioids (particularly oxycodone and morphine) and BTX-A. Data for cannabinoids, tapentadol, drug combinations, and several other antiepileptics, antidepressants and topical drugs were inconclusive. Interpretation Limited efficacy, large placebo responses, inadequate diagnostic criteria and poor phenotypic profiling probably account for modest trial outcomes and should be taken into account in future studies. Funding This study was funded by NeuPSIG.

show abstract

Section: Discussionmentioning

confidence: 99%

Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis

Finnerup

Attal

Haroutounian

et al. 2015

The Lancet Neurology

3,086

2,119

View full text Add to dashboard Cite

show abstract

“…4,10,11,21,23,29,33–35,45,53,60,68,69,72 Among these, the Multidimensional Pain Inventory 33 (MPI) is probably the best known. The MPI emerged from biopsychosocial theory, and studies assessing outcomes based on MPI classification indicate that anatomically distinct disorders (headache, TMD, back pain) respond to treatments similarly within each cluster.…”

Section: Discussionmentioning

confidence: 99%

Identification of clusters of individuals relevant to temporomandibular disorders and other chronic pain conditions

Bair

Gaynor

Slade

et al. 2016

Pain

127

150

View full text Add to dashboard Cite

The classification of most chronic pain disorders gives emphasis to anatomical location of the pain to distinguish one disorder from the other (eg, back pain vs temporomandibular disorder [TMD]) or to define subtypes (eg, TMD myalgia vs arthralgia). However, anatomical criteria overlook etiology, potentially hampering treatment decisions. This study identified clusters of individuals using a comprehensive array of biopsychosocial measures. Data were collected from a case–control study of 1031 chronic TMD cases and 3247 TMD-free controls. Three subgroups were identified using supervised cluster analysis (referred to as the adaptive, pain-sensitive, and global symptoms clusters). Compared with the adaptive cluster, participants in the pain-sensitive cluster showed heightened sensitivity to experimental pain, and participants in the global symptoms cluster showed both greater pain sensitivity and greater psychological distress. Cluster membership was strongly associated with chronic TMD: 91.5% of TMD cases belonged to the pain-sensitive and global symptoms clusters, whereas 41.2% of controls belonged to the adaptive cluster. Temporomandibular disorder cases in the pain-sensitive and global symptoms clusters also showed greater pain intensity, jaw functional limitation, and more comorbid pain conditions. Similar results were obtained when the same methodology was applied to a smaller case–control study consisting of 199 chronic TMD cases and 201 TMD-free controls. During a median 3-year follow-up period of TMD-free individuals, participants in the global symptoms cluster had greater risk of developing first-onset TMD (hazard ratio = 2.8) compared with participants in the other 2 clusters. Cross-cohort predictive modeling was used to demonstrate the reliability of the clusters.

show abstract

“…9,17 Knowledge of these QST profile clusters may find utility in prognosticating the response to treatment with certain neuropathic pain medications. 2 Similarly, a widely variable response to opioid therapy, capsaicin, and ketamine infusion therapy occur among subjects with similar diagnoses. 6 The results of QST profiles of central pain states using simple cohort averages, instead of cluster analysis, may not reflect subtle differences attributed to a discrete phenotype.…”

Section: Discussionmentioning

confidence: 99%

Chronic Opioid Therapy Modifies QST Changes After Ketamine Infusion in Chronic Pain Patients

Maher

Zhang

Ahmed

et al. 2017

The Journal of Pain

View full text Add to dashboard Cite

The long-term effects of opioids on sensitization processes are believed to be mediated through the N-methyl-D-aspartate receptor. Quantitative sensory testing (QST) changes observed after a ketamine infusion have been previously described but the effect that chronic opioids will have is not known. The results of this prospective randomized factorial trial compared the thermal QST changes observed after a .05 mg/kg ketamine infusion or a saline placebo in chronic pain subjects who were either opioid-naive or were chronically using opioids for chronic noncancer pain are presented. No baseline QST differences were noted between the 4 groups at baseline. Comparison of changes preinfusion with postinfusion QST measurements resulted in decreased average change in temporal summation response between opioid subjects who received a placebo compared with those who received a ketamine infusion (−5.22, SD = 9.96 vs 13.81, SD = 19.55; P = .004). Additionally, the average change in temporal summation was decreased among subjects who received a ketamine infusion and were not chronically using opioids compared with subjects who were using chronic opioids and received a placebo infusion (−1.91, SD = 13.25 vs 13.81, SD = 19.55; P = .007). The results indicate that low-dose ketamine infusions produce subtle changes in QST phenotypes that are modified by the chronic use of opioids. This illustrates the potential diagnostic and therapeutic value of ketamine in the setting of chronic opioid use. Perspective: The presented data further our understanding of modulation of sensory perception in the setting of chronic opioid use and the role of the N-methyl-D-aspartate receptor. The use of low-dose ketamine infusions may be useful for the treatment as well as diagnosis of opioid-related neuropathic conditions.

show abstract

Neuropathic pain phenotyping as a predictor of treatment response in painful diabetic neuropathy: Data from the randomized, double-blind, COMBO-DN study

Cited by 118 publications

References 28 publications

Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis

Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis

Identification of clusters of individuals relevant to temporomandibular disorders and other chronic pain conditions

Chronic Opioid Therapy Modifies QST Changes After Ketamine Infusion in Chronic Pain Patients

Contact Info

Product

Resources

About