Motor Cortex Stimulation Reduces Hyperalgesia in an Animal Model of Central Pain

Overview

Journal Pain

Specialties Neurology
Psychiatry

Date 2011 Mar 15

PMID 21396776

Citations 37

Authors

Jessica M Lucas

Yadong Ji

Radi Masri

Affiliations

Soon will be listed here.

Abstract

Electrical stimulation of the primary motor cortex has been used since 1991 to treat chronic neuropathic pain. Since its inception, motor cortex stimulation (MCS) treatment has had varied clinical outcomes. Until this point, there has not been a systematic study of the stimulation parameters that most effectively treat chronic pain, or of the mechanisms by which MCS relieves pain. Here, using a rodent model of central pain, we perform a systematic study of stimulation parameters used for MCS and investigate the mechanisms by which MCS reduces hyperalgesia. Specifically, we study the role of the inhibitory nucleus zona incerta (ZI) in mediating the analgesic effects of MCS. In animals with mechanical and thermal hyperalgesia, we find that stimulation at 50 μA, 50 Hz, and 300 μs square pulses for 30 minutes is sufficient to reverse mechanical and thermal hyperalgesia. We also find that stimulation of the ZI mimics the effects of MCS and that reversible inactivation of ZI blocks the effects of MCS. These findings suggest that the reduction of hyperalgesia may be due to MCS effects on ZI. In an animal model of central pain syndrome, motor cortex stimulation reduces hyperalgesia by activating zona incerta and therefore restoring inhibition in the thalamus.

Citing Articles

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References

Viisanen H, Pertovaara A . Antinociception by motor cortex stimulation in the neuropathic rat: does the locus coeruleus play a role?. Exp Brain Res. 2009; 201(2):283-96. DOI: 10.1007/s00221-009-2038-4. View

Viisanen H, Pertovaara A . Roles of the rostroventromedial medulla and the spinal 5-HT(1A) receptor in descending antinociception induced by motor cortex stimulation in the neuropathic rat. Neurosci Lett. 2010; 476(3):133-7. DOI: 10.1016/j.neulet.2010.04.014. View

Quiton R, Masri R, Thompson S, Keller A . Abnormal activity of primary somatosensory cortex in central pain syndrome. J Neurophysiol. 2010; 104(3):1717-25. PMC: 2944690. DOI: 10.1152/jn.00161.2010. View

Garcia-Larrea L, Peyron R . Motor cortex stimulation for neuropathic pain: From phenomenology to mechanisms. Neuroimage. 2007; 37 Suppl 1:S71-9. DOI: 10.1016/j.neuroimage.2007.05.062. View

Hargreaves K, Dubner R, Brown F, Flores C, Joris J . A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain. 1988; 32(1):77-88. DOI: 10.1016/0304-3959(88)90026-7. View

Peyron R, Faillenot I, Mertens P, Laurent B, Garcia-Larrea L . Motor cortex stimulation in neuropathic pain. Correlations between analgesic effect and hemodynamic changes in the brain. A PET study. Neuroimage. 2006; 34(1):310-21. DOI: 10.1016/j.neuroimage.2006.08.037. View

Canavero S, Bonicalzi V . Cortical stimulation for central pain. J Neurosurg. 1995; 83(6):1117. DOI: 10.3171/jns.1995.83.6.1117. View

Drouot X, Nguyen J, Peschanski M, Lefaucheur J . The antalgic efficacy of chronic motor cortex stimulation is related to sensory changes in the painful zone. Brain. 2002; 125(Pt 7):1660-4. DOI: 10.1093/brain/awf161. View

Mitrofanis J, Mikuletic L . Organisation of the cortical projection to the zona incerta of the thalamus. J Comp Neurol. 1999; 412(1):173-85. View

10.

Deuschl G, Herzog J, Kleiner-Fisman G, Kubu C, Lozano A, Lyons K . Deep brain stimulation: postoperative issues. Mov Disord. 2006; 21 Suppl 14:S219-37. DOI: 10.1002/mds.20957. View

11.

Peyron R, Garcia-Larrea L, Gregoire M, Convers P, Richard A, Lavenne F . Parietal and cingulate processes in central pain. A combined positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) study of an unusual case. Pain. 1999; 84(1):77-87. DOI: 10.1016/S0304-3959(99)00190-6. View

12.

Son U, Kim M, Moon D, Kang J . Motor cortex stimulation in a patient with intractable complex regional pain syndrome type II with hemibody involvement. Case report. J Neurosurg. 2003; 98(1):175-9. DOI: 10.3171/jns.2003.98.1.0175. View

13.

Tsubokawa T, Katayama Y, Yamamoto T, Hirayama T, Koyama S . Treatment of thalamic pain by chronic motor cortex stimulation. Pacing Clin Electrophysiol. 1991; 14(1):131-4. DOI: 10.1111/j.1540-8159.1991.tb04058.x. View

14.

Garcia-Larrea L, Peyron R, Mertens P, Gregoire M, Lavenne F, LE Bars D . Electrical stimulation of motor cortex for pain control: a combined PET-scan and electrophysiological study. Pain. 1999; 83(2):259-73. DOI: 10.1016/s0304-3959(99)00114-1. View

15.

Kuroda R, Kawabata A, Kawao N, Umeda W, Takemura M, Shigenaga Y . Somatosensory cortex stimulation-evoked analgesia in rats: potentiation by NO synthase inhibition. Life Sci. 2000; 66(20):PL271-6. DOI: 10.1016/s0024-3205(00)00525-7. View

16.

Vierck Jr C, Light A . Effects of combined hemotoxic and anterolateral spinal lesions on nociceptive sensitivity. Pain. 1999; 83(3):447-457. DOI: 10.1016/S0304-3959(99)00129-3. View

17.

Lefaucheur J, Drouot X, Menard-Lefaucheur I, Nguyen J . Neuropathic pain controlled for more than a year by monthly sessions of repetitive transcranial magnetic stimulation of the motor cortex. Neurophysiol Clin. 2004; 34(2):91-5. DOI: 10.1016/j.neucli.2004.02.001. View

18.

Ebel H, Rust D, Tronnier V, Boker D, Kunze S . Chronic precentral stimulation in trigeminal neuropathic pain. Acta Neurochir (Wien). 1996; 138(11):1300-6. DOI: 10.1007/BF01411059. View

19.

Neafsey E, Bold E, Haas G, Quirk G, Sievert C, Terreberry R . The organization of the rat motor cortex: a microstimulation mapping study. Brain Res. 1986; 396(1):77-96. DOI: 10.1016/s0006-8993(86)80191-3. View

20.

Saitoh Y, Shibata M, Hirano S, Hirata M, Mashimo T, Yoshimine T . Motor cortex stimulation for central and peripheral deafferentation pain. Report of eight cases. J Neurosurg. 2000; 92(1):150-5. DOI: 10.3171/jns.2000.92.1.0150. View