Do Low Levels of Beta-Endorphin in the Cerebrospinal Fluid Indicate Defective Top-Down Inhibition in Patients with Chronic Neuropathic Pain? A Cross-Sectional, Comparative Study

Bäckryd, Emmanuel; Ghafouri, Bijar; Larsson, Björn; Gerdle, Björn

doi:10.1111/pme.12248

Cited by 27 publications

(26 citation statements)

References 38 publications

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“…There may of course be some false positives among our findings, but all in all it does not seem sensible to dismiss all our results as a gigantic type I error. The MVDA methodology used in the present study is the same as used by the Linköping group in a number of recent peer-reviewed publications in different journals,22,29,62–66 and it is congruent with the principles argued for by Wheelock and Wheelock 28. Finally, in order to ensure the robustness of our statistical methodology, the CSF data of the present study were recomputed using the statistical methodology described by Moen et al32 (with use of false discovery rate); the result of this recomputation was exactly the same as the list presented in Table 1 (TG being the last author of both articles).…”

Section: Discussionmentioning

confidence: 99%

Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma

Bäckryd¹,

Tanum²,

Lind³

et al. 2017

JPR

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178

153

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In addition to central hyperexcitability and impaired top–down modulation, chronic inflammation probably plays a role in the pathophysiology of fibromyalgia (FM). Indeed, on the basis of both animal experiments and human studies involving the analysis of cytokines and other inflammation-related proteins in different body fluids, neuroinflammatory mechanisms are considered to be central to the pathophysiology of many chronic pain conditions. However, concerning FM, previous human plasma/serum and/or cerebrospinal fluid (CSF) cytokine studies have looked only at a few predetermined cytokine candidates. Instead of analyzing only a few substances at a time, we used a new multiplex protein panel enabling simultaneous analysis of 92 inflammation-related proteins. Hence, we investigated the CSF and plasma inflammatory profiles of 40 FM patients compared with CSF from healthy controls (n=10) and plasma from blood donor controls (n=46). Using multivariate data analysis by projection, we found evidence of both neuroinflammation (as assessed in CSF) and chronic systemic inflammation (as assessed in plasma). Two groups of proteins (one for CSF and one for plasma) highly discriminating between patients and controls are presented. Notably, we found high levels of CSF chemokine CX3CL1 (also known as fractalkine). In addition, previous findings concerning IL-8 in FM were replicated, in both CSF and plasma. This is the first time that such an extensive inflammatory profile has been described for FM patients. Hence, FM seems to be characterized by objective biochemical alterations, and the lingering characterization of its mechanisms as essentially idiopathic or even psychogenic should be seen as definitively outdated.

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Section: Discussionmentioning

confidence: 99%

Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma

Bäckryd¹,

Tanum²,

Lind³

et al. 2017

JPR

Self Cite

178

153

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“…Bäckryd et al, found no significant correlation between CSF b endorphin level and use of pain medications in patients with chronic neuropathic pain [9]. However, Tramadol which is a drug with mild opiate properties had evidence from randomized controlled trials showing that tramadol is an effective treatment for neuropathic pain [33].…”

Section: Discussionmentioning

confidence: 99%

“…They concluded that CSF-levels of b-endorphin are not a reflection of its peripheral levels [34]. Also Bäckryd et al, reported that there are probably two functionally different b-endorphin systems: one peripheral (release of b-endorphin by the pituitary into the systemic circulation) and one central (synthesis in hypothalamic pro-opio-melanocortin (POMC) neurons) [9], with an intact blood-brain barrier (BBB) hinders free exchange of b-endorphin between plasma and CSF [35].…”

Section: Discussionmentioning

confidence: 99%

“…In the CNS, beta-endorphins similarly bind muopioid receptors and exert their primary action at presynaptic nerve terminals, they exert their analgesic effect by inhibiting the release of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, resulting in excess production of dopamine, which is associated with pleasure [8],and patients with chronic neuropathic pain were found to have low levels of b-endorphin in the cerebrospinal fluid (CSF),which indicates a defective down modulation of pain in chronic neuropathic pain [9].…”

Section: Introductionmentioning

confidence: 99%

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Beta-endorphin levels in both painful and painless diabetic peripheral neuropathy and its relations to pain characters and severity

Elkhamisy

Khalel

Elbioumy

et al. 2017

Clinical Diabetology

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“…Plasma substance P and β-endorphin were not quantified at the site of stimulation. Also recognize that central versus circulating neuropeptides represent functionally different systems (2,3,14,59). For example, CNS β- endorphin release can also reduce pain via GABAergic inhibition.…”

Section: Strengths and Limitationsmentioning

confidence: 99%

Age Differences in the Time Course and Magnitude of Changes in Circulating Neuropeptides After Pain Evocation in Humans

Riley

Cruz-Almeida

Ribeiro

et al. 2017

The Journal of Pain

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This study tested the hypothesis that older adults would have a stronger response for substance P (facilitatory) but weaker response to β-endorphin (inhibitory), both in magnitude and time-course. Eight younger and 9 older adults underwent 3 experimental sessions using well-validated laboratory pain models: cold pressor task (CPT), contact heat pain (HP), and a non-painful control. Blood was collected through an indwelling catheter at baseline and 3, 15, 30, 45, and 60-minutes post-stimuli administration. Older adults had higher baseline levels of both neuropeptides suggesting increased peripheral activity compared to younger adults. Following CPT, older adults demonstrated a quick and strong release of substance P with dramatic recovery, whereas young adults maintained a constant low-grade response. Unlike substance P, β-endorphin increased between 3 and 15 minutes for both groups with the upsurge substantially higher for older adults. Following HP, younger adults had an immediate surge in circulating substance P and β-endorphin that was more pronounced than among older adults. However, levels of substance P for younger adults slowly tapered whereas they continued to climb for the older adults through 30 minutes. β-endorphin peaked at 30 minutes for both groups and returned to baseline. No changes were observed during the non-painful control.

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Do Low Levels of Beta-Endorphin in the Cerebrospinal Fluid Indicate Defective Top-Down Inhibition in Patients with Chronic Neuropathic Pain? A Cross-Sectional, Comparative Study

Cited by 27 publications

References 38 publications

Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma

Evidence of both systemic inflammation and neuroinflammation in fibromyalgia patients, as assessed by a multiplex protein panel applied to the cerebrospinal fluid and to plasma

Beta-endorphin levels in both painful and painless diabetic peripheral neuropathy and its relations to pain characters and severity

Age Differences in the Time Course and Magnitude of Changes in Circulating Neuropeptides After Pain Evocation in Humans

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