title: Transdural motor cortex stimulation reverses neuropathic pain in rats: a profile of neuronal activation.
abstract: Motor cortex stimulation (MCS) has been used to treat patients with neuropathic pain resistant to other therapeutic approaches; however, the mechanisms of pain control by MCS are still not clearly understood. We have demonstrated that MCS increases the nociceptive threshold of naive conscious rats, with opioid participation. In the present study, the effect of transdural MCS on neuropathic pain in rats subjected to chronic constriction injury of the sciatic nerve was investigated. In addition, the pattern of neuronal activation, evaluated by Fos and Zif268 immunolabel, was performed in the spinal cord and brain sites associated with the modulation of persistent pain. MCS reversed the mechanical hyperalgesia and allodynia induced by peripheral neuropathy. After stimulation, Fos immunoreactivity (Fos-IR) decreased in the dorsal horn of the spinal cord and in the ventral posterior lateral and medial nuclei of the thalamus, when compared to animals with neuropathic pain. Furthermore, the MCS increased the Fos-IR in the periaqueductal gray, the anterior cingulate cortex and the central and basolateral amygdaloid nuclei. Zif268 results were similar to those obtained for Fos, although no changes were observed for Zif268 in the anterior cingulate cortex and the central amygdaloid nucleus after MCS. The present findings suggest that MCS reverts neuropathic pain phenomena in rats, mimicking the effect observed in humans, through activation of the limbic and descending pain inhibitory systems. Further investigation of the mechanisms involved in this effect may contribute to the improvement of the clinical treatment of persistent pain.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil. ropagano@yahoo.com
authors.forename: Rosana L
authors.initials: RL
authors.lastname: Pagano
authors.forename: Danielle V
authors.initials: DV
authors.lastname: Assis
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Clara
authors.forename: Adilson S
authors.initials: AS
authors.lastname: Alves
authors.forename: Camila S
authors.initials: CS
authors.lastname: Dale
authors.forename: Manoel J
authors.initials: MJ
authors.lastname: Teixeira
authors.forename: Erich T
authors.initials: ET
authors.lastname: Fonoff
authors.forename: Luiz R
authors.initials: LR
authors.lastname: Britto
mesh_terms: D000818:Animals; D004599:Electric Stimulation Therapy; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D008297:Male; D009044:Motor Cortex / Q000378:metabolism / Q000503:physiopathology*; D009437:Neuralgia / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D009474:Neurons / Q000502:physiology*; D017288:Pain Threshold / Q000502:physiology; D010487:Periaqueductal Gray / Q000378:metabolism / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000293:injuries*; D016896:Treatment Outcome
chemical_list: D016760:Proto-Oncogene Proteins c-fos