An investigation of metabolome in blood in patients with chronic peripheral, posttraumatic/postsurgical neuropathic pain

Ghafouri, Bijar; Thordeman, Katarina; Hadjikani, Romina; Nord, Anders Bay; Gerdle, Björn; Bäckryd, Emmanuel

doi:10.1038/s41598-022-26405-6

Cited by 5 publications

(7 citation statements)

References 28 publications

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“…There are few NMR metabolomics studies on neuropathic pain in general, and on CSF in particular. We have previously reported interesting NMR metabolomic findings in blood from the same patients with chronic neuropathic pain [ 16 ]. In that study, 50 out of 326 features in blood significantly contributed to group separation between patients and healthy controls, the significant metabolites being involved in inflammation, CNS functioning and neural signaling [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…We have previously reported interesting NMR metabolomic findings in blood from the same patients with chronic neuropathic pain [ 16 ]. In that study, 50 out of 326 features in blood significantly contributed to group separation between patients and healthy controls, the significant metabolites being involved in inflammation, CNS functioning and neural signaling [ 16 ]. In the present CSF study, the “metabolomic trace” of the treatment given to patients had a much higher magnitude than differences due to chronic pain pathophysiology.…”

Section: Discussionmentioning

confidence: 99%

“…As reported in previously published papers [ 8 , 16 , 22 , 23 ], the nerve injury that was deemed to cause the neuropathic pain was classified using the International Classification of Diseases version 10 (ICD-10) (see Table 1 ). Four patients suffered from peripheral neuropathic pain projected to the upper extremity, and twelve from peripheral neuropathic pain projected to the lower extremity.…”

Section: Methodsmentioning

confidence: 99%

“…CSF samples was mixed (5:1) with phosphate buffer solution containing 1.5 M KH 2 PO 4 , 580 µM TSP-d4, NaN 3 , D 2 O, pH 7.4 and transferred to 3 mm NMR tubes. The samples were analyzed at the Swedish Nuclear Magnetic Resonance (NMR) Centre in Gothenburg using an Oxford 800 Mhz magnet equipped with a Bruker Avance III HD console, 3 mm TCI cryoprobe and a cooled Sample Jet auto sampler (Bruker BioSpin, Fällanden, Switzerland), as described previously [ 16 ]. Generated data from NMR spectrometer were processed in TopSpin3.5pl7 (Bruker BioSpin, Fällanden, Switzerland).…”

Section: Methodsmentioning

confidence: 99%

“…Nuclear magnetic resonance (NMR) spectroscopy is a useful technique for the metabolomic study of different diseases including chronic pain conditions, such as neuropathic pain or fibromyalgia. NMR enables the detection of several hundred small molecules in body fluids such as CSF, blood or urine [ 15 , 16 , 17 , 18 , 19 ]. In a previous NMR metabolomic study, we compared blood from patients suffering from chronic neuropathic pain with healthy controls, finding that several of the metabolites that significantly differed between groups were involved in inflammatory processes, while others were important for CNS functioning and neural signaling [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Cerebrospinal Fluid Metabolomics Identified Ongoing Analgesic Medication in Neuropathic Pain Patients

Bäckryd,

Thordeman,

Gerdle

et al. 2023

Biomedicines

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Background: Cerebrospinal fluid (CSF) can reasonably be hypothesized to mirror central nervous system pathophysiology in chronic pain conditions. Metabolites are small organic molecules with a low molecular weight. They are the downstream products of genes, transcripts and enzyme functions, and their levels can mirror diseased metabolic pathways. The aim of this metabolomic study was to compare the CSF of patients with chronic neuropathic pain (n = 16) to healthy controls (n = 12). Methods: Nuclear magnetic resonance spectroscopy was used for analysis of the CSF metabolome. Multivariate data analysis by projection discriminant analysis (OPLS-DA) was used to separate information from noise and minimize the multiple testing problem. Results: The significant OPLS-DA model identified 26 features out of 215 as important for group separation (R2 = 0.70, Q2 = 0.42, p = 0.017 by CV-ANOVA; 2 components). Twenty-one out of twenty-six features were statistically significant when comparing the two groups by univariate statistics and remained significant at a false discovery rate of 10%. For six out of the top ten metabolite features, the features were absent in all healthy controls. However, these features were related to medication, mainly acetaminophen (=paracetamol), and not to pathophysiological processes. Conclusion: CSF metabolomics was a sensitive method to detect ongoing analgesic medication, especially acetaminophen.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Cerebrospinal Fluid Metabolomics Identified Ongoing Analgesic Medication in Neuropathic Pain Patients

Bäckryd,

Thordeman,

Gerdle

et al. 2023

Biomedicines

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Tryptophan metabolism and small fibre neuropathy: a correlation study

Kushibiki,

Mizukami,

Osonoi

et al. 2024

Brain Communications

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Small nerve fibres located in the epidermis sense pain. Dysfunction of these fibres decreases the pain threshold known as small fibre neuropathy. Diabetes mellitus is accompanied by metabolic changes other than glucose, synergistically eliciting small fibre neuropathy. These findings suggest that various metabolic changes may be involved in small fibre neuropathy. Herein, we explored the correlation between pain sensation and changes in plasma metabolites in healthy Japanese subjects. The pain threshold evaluated from the intraepidermal electrical stimulation was used to quantify pain sensation in a total of 1021 individuals in the 2017 Iwaki Health Promotion Project. Participants with a pain threshold evaluated from the intraepidermal electrical stimulation index <0.20 mA were categorized into the pain threshold evaluated from the intraepidermal electrical stimulation index-low group (n = 751); otherwise, they were categorized into the pain threshold evaluated from the intraepidermal electrical stimulation index-high group (n = 270). Metabolome analysis of plasma was conducted using capillary electrophoresis time-of-flight mass spectrometry. The metabolite set enrichment analysis revealed that the metabolism of tryptophan was significantly correlated with the pain threshold evaluated from the intraepidermal electrical stimulation index in all participants (P < 0.05). The normalized level of tryptophan was significantly decreased in participants with a high pain threshold evaluated from the intraepidermal electrical stimulation index. In addition to univariate linear regression analyses, the correlation between tryptophan concentration and the pain threshold evaluated from the intraepidermal electrical stimulation index remained significant after adjustment for multiple factors (β = −0.07615, P < 0.05). These findings indicate that specific metabolic changes are involved in the deterioration of pain thresholds. Here, we show that abnormal tryptophan metabolism is significantly correlated with an elevated pain threshold evaluated from the intraepidermal electrical stimulation index in the Japanese population. This correlation provides insight into the pathology and clinical application of small fibre neuropathy.

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Metabolomic profiling of pediatric post‐tonsillectomy pain: A proof‐of‐concept study

Mpody,

Patel,

Smoyer

et al. 2024

Pediatric Anesthesia

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IntroductionTonsillectomies are among the most common surgical procedures in children, with over 500 000 cases annually in the United States. Despite universal administration of intraoperative opioid analgesia, three out of five children undergoing tonsillectomy report moderate‐to‐severe pain upon recovering from anesthesia. The underlying molecular mechanisms of post‐tonsillectomy pain are not well understood, limiting the development of targeted treatment strategies. Our study aimed to identify candidate serum metabolites associated with varying severity of post‐tonsillectomy pain.MethodsVenous blood samples and pain scores were obtained from 34 children undergoing tonsillectomy ± adenoidectomy, and metabolomic analysis was performed. Supervised orthogonal projections to latent structures discriminant analysis were employed to identify differentially expressed metabolites between children with severe and mild pain, as well as between moderate and mild pain.ResultsPain scores differentiated children as mild (n = 6), moderate (n = 14), or severe (n = 14). Four metabolites (fatty acid 18:0(OH), thyroxine, phosphatidylcholine 38:5, and branched fatty acids C27H54O3) were identified as candidate biomarkers that differentiated severe vs. mild post‐tonsillectomy pain, the combination of which yielded an AUC of 0.91. Similarly, four metabolites (sebacic acid, dicarboxylic acids C18H34O4, hydroxy fatty acids C18H34O3, and myristoleic acid) were identified as candidate biomarkers that differentiated moderate vs. mild post‐tonsillectomy pain, with AUC values ranging from 0.85 to 0.95.ConclusionThis study identified novel candidate biomarker panels that effectively differentiated varying severity of post‐tonsillectomy pain. Further research is needed to validate these data and to explore their clinical implications for personalized pain management in children undergoing painful surgeries.

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An investigation of metabolome in blood in patients with chronic peripheral, posttraumatic/postsurgical neuropathic pain

Cited by 5 publications

References 28 publications

Cerebrospinal Fluid Metabolomics Identified Ongoing Analgesic Medication in Neuropathic Pain Patients

Cerebrospinal Fluid Metabolomics Identified Ongoing Analgesic Medication in Neuropathic Pain Patients

Tryptophan metabolism and small fibre neuropathy: a correlation study

Metabolomic profiling of pediatric post‐tonsillectomy pain: A proof‐of‐concept study

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