Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Neurology
Published in: BMC Neurology 1/2018

Open Access 01-12-2018 | Research article

The effect of occipital nerve field stimulation on the descending pain pathway in patients with fibromyalgia: a water PET and EEG imaging study

Authors: Shaheen Ahmed, Mark Plazier, Jan Ost, Gaetane Stassijns, Steven Deleye, Sarah Ceyssens, Patrick Dupont, Sigrid Stroobants, Steven Staelens, Dirk De Ridder, Sven Vanneste

Published in: BMC Neurology | Issue 1/2018

Login to get access

Abstract

Background

Fibromyalgia is a chronic disorder characterized by widespread musculoskeletal pain accompanied by fatigue, sleep, memory, and mood problems. Recently, occipital nerve field stimulation (ONS) has been proposed as an effective potential treatment for fibromyalgia-related pain. The aim of this study is to unravel the neural mechanism behind occipital nerve stimulation’s ability to suppress pain in fibromyalgia patients.

Materials and methods

Seven patients implanted with subcutaneous electrodes in the C2 dermatoma were enrolled for a Positron Emission Tomography (PET) H215O activation study. These seven patients were selected from a cohort of 40 patients who were part of a double blind, placebo-controlled study followed by an open label follow up at six months. The H215O PET scans were taken during both the “ON” (active stimulation) and “OFF” (stimulating device turned off) conditions. Electroencephalogram (EEG) data were also recorded for the implanted fibromyalgia patients during both the “ON” and “OFF” conditions.

Results

Relative to the “OFF” condition, ONS stimulation resulted in activation in the dorsal lateral prefrontal cortex, comprising the medial pain pathway, the ventral medial prefrontal cortex, and the bilateral anterior cingulate cortex as well as parahippocampal area, the latter two of which comprise the descending pain pathway. Relative deactivation was observed in the left somatosensory cortex, constituting the lateral pain pathway as well as other sensory areas such as the visual and auditory cortex. The EEG results also showed increased activity in the descending pain pathway. The pregenual anterior cingulate cortex extending into the ventral medial prefrontal cortex displayed this increase in the theta, alpha1, alpha2, beta1, and beta2 frequency bands.

Conclusion

PET shows that ONS exerts its effect via activation of the descending pain inhibitory pathway and the lateral pain pathway in fibromyalgia, while EEG shows activation of those cortical areas that could be responsible for descending inhibition system recruitment.

Trial Registration

This study is registered with ClinicalTrials.​gov, number NCT00917176 (June 10, 2009).
Literature
1.
Wolfe F, et al. Aspects of fibromyalgia in the general population: sex, pain threshold, and fibromyalgia symptoms. J Rheumatol. 1995;22(1):151–6.PubMed
2.
3.
4.
Berger A, et al. Patterns of healthcare utilization and cost in patients with newly diagnosed fibromyalgia. Am J Manag Care. 2010;16(5 Suppl):S126–37.PubMed
5.
Perrot S, et al. Societal and individual burden of illness among fibromyalgia patients in France: association between disease severity and OMERACT core domains. BMC Musculoskelet Disord. 2012;13:22.PubMedPubMedCentralCrossRef
6.
Sauer K, Kemper C, Glaeske G. Fibromyalgia syndrome: prevalence, pharmacological and non-pharmacological interventions in outpatient health care. An analysis of statutory health insurance data. Joint Bone Spine. 2011;78(1):80–4.PubMedCrossRef
7.
Chinn S, Caldwell W, Gritsenko K. Fibromyalgia pathogenesis and treatment options update. Curr Pain Headache Rep. 2016;20(4):25.PubMedCrossRef
8.
Marlow NM, Bonilha HS, Short EB. Efficacy of transcranial direct current stimulation and repetitive transcranial magnetic stimulation for treating fibromyalgia syndrome: a systematic review. Pain Practice. 2013;13(2):131–45.PubMedCrossRef
9.
Taylor AG, et al. Cranial electrical stimulation improves symptoms and functional status in individuals with fibromyalgia. Pain Management Nursing. 2013;14(4):327–35.PubMedCrossRef
10.
Thimineur M, De Ridder D. C2 area neurostimulation: a surgical treatment for fibromyalgia. Pain Med. 2007;8(8):639–46.PubMedCrossRef
11.
Plazier M, et al. Peripheral nerve stimulation for fibromyalgia, in Peripheral Nerve Stimulation. Basel: Karger Publishers; 2011. p. 133–46.CrossRef
12.
Plazier M, et al. Occipital nerve stimulation in fibromyalgia: a double-blind placebo-controlled pilot study with a six-month follow-up. Neuromodulation: Technology at the Neural Interface. 2014;17(3):256–64.CrossRef
13.
Weiner RL, Reed KL. Peripheral neurostimulation for control of intractable occipital neuralgia. Neuromodulation: Technology at the Neural Interface. 1999;2(3):217–21.CrossRef
14.
Le Doare K, et al. Occipital afferent activation of second order neurons in the trigeminocervical complex in rat. Neurosci Lett. 2006;403(1):73–7.PubMedCrossRef
15.
Goadsby PJ, Knight YE, Hoskin KL. Stimulation of the greater occipital nerve increases metabolic activity in the trigeminal nucleus caudalis and cervical dorsal horn of the cat. Pain. 1997;73(1):23–8.PubMedCrossRef
16.
Busch V, et al. Functional connectivity between trigeminal and occipital nerves revealed by occipital nerve blockade and nociceptive blink reflexes. Cephalalgia. 2006;26(1):50–5.PubMedCrossRef
17.
Magis D, et al. Occipital nerve stimulation for drug-resistant chronic cluster headache: a prospective pilot study. The Lancet Neurology. 2007;6(4):314–21.PubMedCrossRef
18.
Kovacs S, et al. Central effects of occipital nerve electrical stimulation studied by functional magnetic resonance imaging. Neuromodulation: Technology at the Neural Interface. 2011;14(1):46–57.CrossRef
19.
De Ridder D, Vanneste S. Occipital nerve field transcranial direct current stimulation normalizes imbalance between pain detecting and pain inhibitory pathways in fibromyalgia. Neurotherapeutics. 2016:1–18.
20.
Matharu MS, et al. Central neuromodulation in chronic migraine patients with suboccipital stimulators: a PET study. Brain. 2004;127(1):220–30.PubMedCrossRef
21.
22.
Price DD. Psychological and neural mechanisms of the affective dimension of pain. Science. 2000;288(5472):1769–72.PubMedCrossRef
23.
24.
25.
Jensen KB, et al. Overlapping structural and functional brain changes in patients with long-term exposure to fibromyalgia pain. Arthritis Rheum. 2013;65(12):3293–303.PubMedPubMedCentralCrossRef
26.
Schmidt-Wilcke T, et al. Resting state connectivity correlates with drug and placebo response in fibromyalgia patients. Neuroimage Clin. 2014;6:252–61.PubMedPubMedCentralCrossRef
27.
28.
Wolfe F, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the multicenter criteria committee. Arthritis Rheum. 1990;33(2):160–72.PubMedCrossRef
29.
Bennett R. The fibromyalgia impact questionnaire (FIQ): a review of its development, current version, operating characteristics and uses. Clin Exp Rheumatol. 2005;23(5 Suppl 39):S154–62.PubMed
30.
McCracken LM. “Attention” to pain in persons with chronic pain: a behavioral approach. Behav Ther. 1997;28(2):271–84.CrossRef
31.
Neuling T, et al. Friends, not foes: magnetoencephalography as a tool to uncover brain dynamics during transcranial alternating current stimulation. Neuroimage. 2015;118:406–13.PubMedCrossRef
32.
Neuling T, et al. Faith and oscillations recovered: on analyzing EEG/MEG signals during tACS. Neuroimage. 2017;147:960–3.PubMedCrossRef
33.
Congedo, M., EureKa! (version 3.0) [computer software]. Knoxville, TN: NovaTech EEG Inc. freeware available at www.​NovaTechEEG. 2002.
34.
Pascual-Marqui RD. Standardized low-resolution brain electromagnetic tomography (sLORETA): technical details. Methods Find Exp Clin Pharmacol. 2002;(24 Suppl D):5–12.
35.
Jurcak V, Tsuzuki D, Dan I. 10/20, 10/10, and 10/5 systems revisited: their validity as relative head-surface-based positioning systems. Neuroimage. 2007;34(4):1600–11.PubMedCrossRef
36.
Fuchs M, et al. A standardized boundary element method volume conductor model. Clin Neurophysiol. 2002;113(5):702–12.PubMedCrossRef
37.
Mazziotta JC, et al. A probabilistic atlas of the human brain: theory and rationale for its development. Neuroimage. 1995;2(2):89–101.PubMedCrossRef
38.
Nichols TE, Holmes AP. Nonparametric permutation tests for functional neuroimaging: a primer with examples. Hum Brain Mapp. 2002;15(1):1–25.PubMedCrossRef
39.
Kong J, et al. Exploring the brain in pain: activations, deactivations and their relation. Pain. 2010;148(2):257–67.PubMedCrossRef
40.
41.
Eippert F, et al. Activation of the opioidergic descending pain control system underlies placebo analgesia. Neuron. 2009;63(4):533–43.PubMedCrossRef
42.
Jensen KB, et al. Overlapping structural and functional brain changes in patients with long-term exposure to fibromyalgia pain. Arthritis & Rheumatism. 2013;65(12):3293–303.CrossRef
43.
44.
Truini A, et al. Abnormal resting state functional connectivity of the periaqueductal grey in patients with fibromyalgia. Clin Exp Rheumatol. 2016;34(2 Suppl 96):S129–33.PubMed
45.
Xie Y-f, Huo F-q, Tang J-s. Cerebral cortex modulation of pain. Acta Pharmacol Sin. 2009;30(1):31–41.PubMedCrossRef
46.
47.
Cieslik EC, et al. Is there “one” DLPFC in cognitive action control? Evidence for heterogeneity from co-activation-based parcellation. Cereb Cortex. 2013;23:2677–789.PubMedCrossRef
48.
49.
Kouneiher F, Charron S, Koechlin E. Motivation and cognitive control in the human prefrontal cortex. Nat Neurosci. 2009;12(7):939–45.PubMedCrossRef
50.
Liu Y, et al. Top-down modulation of neural activity in anticipatory visual attention: control mechanisms revealed by simultaneous EEG-fMRI. Cereb Cortex. 2016;26:517–29.PubMedCrossRef
51.
52.
Barbey AK, Koenigs M, Grafman J. Dorsolateral prefrontal contributions to human working memory. Cortex. 2013;49(5):1195–205.PubMedCrossRef
53.
Treadway MT, et al. Corticolimbic gating of emotion-driven punishment. Nat Neurosci. 2014;17(9):1270–5.PubMedCrossRef
54.
55.
56.
Lorenz J, Minoshima S, Casey K. Keeping pain out of mind: the role of the dorsolateral prefrontal cortex in pain modulation. Brain. 2003;126(5):1079–91.PubMedCrossRef
57.
De Ridder D, et al. Burst spinal cord stimulation for limb and back pain. World neurosurgery. 2013;80(5):642–9.PubMedCrossRef
58.
De Ridder D, et al. Burst spinal cord stimulation: toward paresthesia-free pain suppression. Neurosurgery. 2010;66(5):986–90.PubMedCrossRef
59.
Courtney P, et al. Improved pain relief with burst spinal cord stimulation for two weeks in patients using tonic stimulation: results from a small clinical study. Neuromodulation: Technology at the Neural Interface. 2015;18(5):361–6.CrossRef
60.
Schu S, et al. A prospective, randomised, double-blind, placebo-controlled study to examine the effectiveness of burst spinal cord stimulation patterns for the treatment of failed back surgery syndrome. Neuromodulation: Technology at the Neural Interface. 2014;17(5):443–50.CrossRef
61.
Aminoff E, Gronau N, Bar M. The parahippocampal cortex mediates spatial and nonspatial associations. Cereb Cortex. 2007;17(7):1493–503.PubMedCrossRef
62.
Bar M, Aminoff E, Ishai A. Famous faces activate contextual associations in the parahippocampal cortex. Cereb Cortex. 2008;18(6):1233–8.PubMedCrossRef
63.
Bar M, Aminoff E, Schacter DL. Scenes unseen: the parahippocampal cortex intrinsically subserves contextual associations, not scenes or places per se. J Neurosci. 2008;28(34):8539–44.PubMedPubMedCentralCrossRef
64.
Eichenbaum H, Lipton PA. Towards a functional organization of the medial temporal lobe memory system: role of the parahippocampal and medial entorhinal cortical areas. Hippocampus. 2008;18(12):1314–24.PubMedPubMedCentralCrossRef
65.
Ranganath C, Ritchey M. Two cortical systems for memory-guided behaviour. Nat Rev Neurosci. 2012;13(10):713–26.PubMedCrossRef
66.
Wood PB, et al. Hippocampal metabolite abnormalities in fibromyalgia: correlation with clinical features. J Pain. 2009;10(1):47–52.PubMedCrossRef
67.
Wood PB, Ledbetter CR, Patterson JC 2nd. Changes in hippocampal metabolites after effective treatment for fibromyalgia: a case study. Clin J Pain. 2009;25(9):810–4.PubMedCrossRef
68.
69.
70.
Kamping S, et al. Deficient modulation of pain by a positive emotional context in fibromyalgia patients. Pain. 2013;154(9):1846–55.PubMedCrossRef
71.
De Ridder D, Vanneste S. Burst and tonic spinal cord stimulation: different and common brain mechanisms. Neuromodulation. 2016;19(1):47–59.PubMedCrossRef
72.
73.
Schwedt TJ, et al. Enhanced pain-induced activity of pain-processing regions in a case-control study of episodic migraine. Cephalalgia. 2014;34(12):947–58.PubMedPubMedCentralCrossRef
74.
Glass JM, et al. Executive function in chronic pain patients and healthy controls: different cortical activation during response inhibition in fibromyalgia. J Pain. 2011;12(12):1219–29.PubMedPubMedCentralCrossRef
75.
76.
Lambert GA, et al. Effect of cortical spreading depression on activity of trigeminovascular sensory neurons. Cephalalgia. 1999;19(7):631–8.PubMedCrossRef
77.
Vanneste S, et al. Transcutaneous electrical nerve stimulation (TENS) of upper cervical nerve (C2) for the treatment of somatic tinnitus. Exp Brain Res. 2010;204(2):283–7.PubMedCrossRef
78.
De Ridder D, Vanneste S. Multitarget surgical neuromodulation: combined C2 and auditory cortex implantation for tinnitus. Neurosci Lett. 2015;591:202–6.PubMedCrossRef
79.
De Ridder D, et al. Surgical brain modulation for tinnitus: the past, present and future. J Neurosurg Sci. 2012;56(4):323–40.PubMed
80.
Cagnie B, et al. Central sensitization in fibromyalgia? A systematic review on structural and functional brain MRI. Semin Arthritis Rheum. 2014;44(1):68–75.PubMedCrossRef
81.
Friebel U, Eickhoff SB, Lotze M. Coordinate-based meta-analysis of experimentally induced and chronic persistent neuropathic pain. Neuroimage. 2011;58(4):1070–80.PubMedCrossRef
82.
Price DD. Neuroscience - psychological and neural mechanisms of the affective dimension of pain. Science. 2000;288(5472):1769–72.PubMedCrossRef
83.
84.
Pujol J, et al. The contribution of sensory system functional connectivity reduction to clinical pain in fibromyalgia. Pain. 2014;155(8):1492–503.PubMedCrossRef
85.
De Ridder D, Vanneste S. Occipital nerve field transcranial direct current stimulation normalizes imbalance between pain detecting and pain inhibitory pathways in fibromyalgia. Neurotherapeutics. 2016.
86.
Lim M, et al. Disinhibition of the primary somatosensory cortex in patients with fibromyalgia. Pain. 2015;156(4):666–74.PubMedCrossRef
87.
88.
89.
Amanzio M, et al. Activation likelihood estimation meta-analysis of brain correlates of placebo analgesia in human experimental pain. Hum Brain Mapp. 2013;34(3):738–52.PubMed
90.
Benedetti F, Amanzio M. Mechanisms of the placebo response. Pulm Pharmacol Ther. 2013;26(5):520–3.PubMedCrossRef
91.
92.
Buckner RL, Andrews-Hanna JR, Schacter DL. The brain's default network: anatomy, function, and relevance to disease. Ann N Y Acad Sci. 2008;1124:1–38.PubMedCrossRef
93.
94.
95.
Bzdok D, et al. Subspecialization in the human posterior medial cortex. Neuroimage. 2015;106:55–71.PubMedCrossRef
96.
Leech R, Sharp DJ. The role of the posterior cingulate cortex in cognition and disease. Brain. 2014;137(Pt 1):12–32.PubMedCrossRef
97.
Metadata
Title
The effect of occipital nerve field stimulation on the descending pain pathway in patients with fibromyalgia: a water PET and EEG imaging study
Authors
Shaheen Ahmed
Mark Plazier
Jan Ost
Gaetane Stassijns
Steven Deleye
Sarah Ceyssens
Patrick Dupont
Sigrid Stroobants
Steven Staelens
Dirk De Ridder
Sven Vanneste
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2018
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-018-1190-5

Other articles of this Issue 1/2018

BMC Neurology 1/2018 Go to the issue

Research article

Neuromyelitis optica spectrum disorders with and without connective tissue disorders

Case report

Bilateral oculomotor ocular neuromyotonia: a case report

Research article

Feasibility trial of an early therapy in perinatal stroke (eTIPS)

Case report

A case report of rigidity and recurrent lower limb myoclonus: progressive encephalomyelitis rigidity and myoclonus syndrome, a chameleon

Case report

Cerebral infarcts associated with adenomyosis: a rare risk factor for stroke in middle-aged women: a case series

Research article

Evaluation of patients with relapsing-remitting multiple sclerosis using tract-based spatial statistics analysis: diffusion kurtosis imaging