Safety and Feasibility of Deep Brain Stimulation of the Anterior Cingulate and Thalamus in Chronic Refractory Neuropathic Pain: a Pilot and Randomized Study

Overview

Journal J Headache Pain

Publisher Biomed Central

Date 2025 Feb 18

PMID 39962366

Authors

Denys Fontaine

Aurelie Leplus

Anne Donnet

Nelly Darmon

Anne Balossier

Bruno Giordana

Benoit Simonet

Petru Isan

Jean Regis

Michel Lanteri-Minet

Affiliations

Soon will be listed here.

Abstract

Background: Deep Brain Stimulation (DBS) of the anterior cingulum has been recently proposed to treat refractory chronic pain but its safety and its efficacy have not been evaluated in controlled conditions. Our objective was to evaluate the respective feasibility and safety of sensory thalamus (Thal-DBS) combined with anterior cingulate (ACC-DBS) DBS in patients suffering from chronic neuropathic pain.

Methods: We conducted a bicentric study (clinicaltrials.gov NCT03399942) in patients suffering from medically-refractory chronic unilateral neuropathic pain surgically implanted with both unilateral Thal-DBS and bilateral ACC-DBS, to evaluate successively: Thal-DBS only; combined Thal-DBS and ACC-DBS; ACC-DBS "on" and "off" stimulation periods in randomized cross-over double-blinded conditions; and a 1-year open phase. Safety and efficacy were evaluated by repeated neurological examination, psychiatric assessment, comprehensive assessment of cognitive and affective functioning. Changes on pain intensity (Visual Analogic Scale) and quality of life (EQ-5D scale) were used to evaluate DBS efficacy.

Results: All the patients (2 women, 6 men, mean age 52,1) completed the study. Adverse events were: epileptic seizure (2), transient motor or attention (2), persistent gait disturbances (1), sleep disturbances (1). No patient displayed significant cognitive or affective change. Compared to baseline, the quality of life (EQ-5D utility score) was significantly improved during the ACC-DBS "On" stimulation period (p = 0,039) and at the end of the study (p = 0,034).

Conclusion: This pilot study confirmed the safety of anterior cingulate DBS alone or in combination with thalamic stimulation and suggested that it might improve quality of life of patients with chronic refractory neuropathic pain.

Trial Registration: The study has been registered on 20,180,117 (clinicaltrials.gov NCT03399942).

References

Rainville P . Brain mechanisms of pain affect and pain modulation. Curr Opin Neurobiol. 2002; 12(2):195-204. DOI: 10.1016/s0959-4388(02)00313-6. View

Boccard S, FitzGerald J, Pereira E, Moir L, van Hartevelt T, Kringelbach M . Targeting the affective component of chronic pain: a case series of deep brain stimulation of the anterior cingulate cortex. Neurosurgery. 2014; 74(6):628-35. DOI: 10.1227/NEU.0000000000000321. View

Bittar R, Kar-Purkayastha I, Owen S, Bear R, Green A, Wang S . Deep brain stimulation for pain relief: a meta-analysis. J Clin Neurosci. 2005; 12(5):515-9. DOI: 10.1016/j.jocn.2004.10.005. View

Coffey R . Deep brain stimulation for chronic pain: results of two multicenter trials and a structured review. Pain Med. 2004; 2(3):183-92. DOI: 10.1046/j.1526-4637.2001.01029.x. View

Wager T, Atlas L, Botvinick M, Chang L, Coghill R, Davis K . Pain in the ACC?. Proc Natl Acad Sci U S A. 2016; 113(18):E2474-5. PMC: 4983860. DOI: 10.1073/pnas.1600282113. View

Hassenbusch S, Pillay P, Barnett G . Radiofrequency cingulotomy for intractable cancer pain using stereotaxis guided by magnetic resonance imaging. Neurosurgery. 1990; 27(2):220-3. DOI: 10.1097/00006123-199008000-00008. View

Levi V, Cordella R, DAmmando A, Tringali G, Dones I, Messina G . Dorsal anterior cingulate cortex (ACC) deep brain stimulation (DBS): a promising surgical option for the treatment of refractory thalamic pain syndrome (TPS). Acta Neurochir (Wien). 2019; 161(8):1579-1588. DOI: 10.1007/s00701-019-03975-5. View

Shackman A, Salomons T, Slagter H, Fox A, Winter J, Davidson R . The integration of negative affect, pain and cognitive control in the cingulate cortex. Nat Rev Neurosci. 2011; 12(3):154-67. PMC: 3044650. DOI: 10.1038/nrn2994. View

Poquet N, Lin C . The Brief Pain Inventory (BPI). J Physiother. 2015; 62(1):52. DOI: 10.1016/j.jphys.2015.07.001. View

10.

Nowacki A, Zhang D, Sarica C, Elias G, Bajaj S, Franzini A . Thalamic deep brain stimulation for central poststroke pain syndrome: an international multicenter study. J Neurosurg. 2025; :1-12. DOI: 10.3171/2024.8.JNS24742. View

11.

Leplus A, Lanteri-Minet M, Donnet A, Darmon N, Regis J, Fontaine D . Treatment of Chronic Refractory Pain by Combined Deep Brain Stimulation of the Anterior Cingulum and Sensory Thalamus (EMOPAIN Study): Rationale and Protocol of a Feasibility and Safety Study. Brain Sci. 2022; 12(9). PMC: 9496880. DOI: 10.3390/brainsci12091116. View

12.

Melzack R . The McGill Pain Questionnaire: major properties and scoring methods. Pain. 1975; 1(3):277-299. DOI: 10.1016/0304-3959(75)90044-5. View

13.

Caruana F, Gerbella M, Avanzini P, Gozzo F, Pelliccia V, Mai R . Motor and emotional behaviours elicited by electrical stimulation of the human cingulate cortex. Brain. 2018; 141(10):3035-3051. DOI: 10.1093/brain/awy219. View

14.

Rosner J, de Andrade D, Davis K, Gustin S, Kramer J, Seal R . Central neuropathic pain. Nat Rev Dis Primers. 2023; 9(1):73. PMC: 11329872. DOI: 10.1038/s41572-023-00484-9. View

15.

Bouhassira D, Attal N . Diagnosis and assessment of neuropathic pain: the saga of clinical tools. Pain. 2010; 152(3 Suppl):S74-S83. DOI: 10.1016/j.pain.2010.11.027. View

16.

Boccard S, Prangnell S, Pycroft L, Cheeran B, Moir L, Pereira E . Long-Term Results of Deep Brain Stimulation of the Anterior Cingulate Cortex for Neuropathic Pain. World Neurosurg. 2017; 106:625-637. DOI: 10.1016/j.wneu.2017.06.173. View

17.

Peyron R, Laurent B, Garcia-Larrea L . Functional imaging of brain responses to pain. A review and meta-analysis (2000). Neurophysiol Clin. 2000; 30(5):263-88. DOI: 10.1016/s0987-7053(00)00227-6. View

18.

Shirvalkar P, Prosky J, Chin G, Ahmadipour P, Sani O, Desai M . First-in-human prediction of chronic pain state using intracranial neural biomarkers. Nat Neurosci. 2023; 26(6):1090-1099. PMC: 10330878. DOI: 10.1038/s41593-023-01338-z. View

19.

Bouhassira D, Lanteri-Minet M, Attal N, Laurent B, Touboul C . Prevalence of chronic pain with neuropathic characteristics in the general population. Pain. 2007; 136(3):380-387. DOI: 10.1016/j.pain.2007.08.013. View

20.

Zigmond A, SNAITH R . The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983; 67(6):361-70. DOI: 10.1111/j.1600-0447.1983.tb09716.x. View