title: Spinal segmental and supraspinal mechanisms underlying the pain-relieving effects of spinal cord stimulation: an experimental study in a rat model of neuropathy.
abstract: Spinal cord stimulation (SCS) may alleviate certain forms of neuropathic pain; its mechanisms of action are, however, not fully understood. Previous studies have mainly been focused onto segmental spinal mechanisms, though there is evidence indicating a supraspinal involvement. This study aims to evaluate the relative importance of segmental and supraspinal mechanisms related to the activation of the dorsal columns (DCs). Rats were used to induce the spared nerve injury neuropathy and simultaneously subjected to chronic bilateral DC lesions at the C6-C8 level. Two pairs of miniature electrodes were implanted in each animal, with a monopolar system placed in the dorsal epidural space at a low thoracic level (below lesion) and a bipolar system placed onto the dorsal column nuclei (above lesion). Stimulation (50 Hz, 0.2 ms, 2-4V, 5 min) was applied via either type of electrodes, and tests for sensitivity to tactile and thermal stimuli were used to assess its inhibitory effects. Various receptor antagonists {bicuculline (GABA(A)), saclofen (GABA(B)), ketanserine (5HT(2)), methysergide (5HT(1-2)), phentolamine (α-adrenergic), propranolol (β-adrenergic), sulpiride (D(2)/D(3) dopamine) or saline were injected prior to the SCS. Rostral and caudal stimulations produced a comparable inhibition of neuropathic manifestations, and these effects were attenuated by about 50% after DC lesions. Pretreatment with the various receptor antagonists differentially influenced the effects of rostral and caudal stimulation. Our findings suggest that both supraspinal and segmental mechanisms are activated by SCS, and that in this model with DC lesions, rostral and caudal stimulations may activate different synaptic circuitries and transmitter systems.
authors.affiliation: Department of Anatomy, Cell Biology and Physiology, American University of Beirut, Lebanon.
authors.forename: J
authors.initials: J
authors.lastname: Barchini
authors.forename: S
authors.initials: S
authors.lastname: Tchachaghian
authors.forename: F
authors.initials: F
authors.lastname: Shamaa
authors.forename: S J
authors.initials: SJ
authors.lastname: Jabbur
authors.forename: B A
authors.initials: BA
authors.lastname: Meyerson
authors.forename: Z
authors.initials: Z
authors.lastname: Song
authors.forename: B
authors.initials: B
authors.lastname: Linderoth
authors.forename: N E
authors.initials: NE
authors.lastname: Saadé
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000627:therapeutic use; D001640:Bicuculline / Q000627:therapeutic use; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology; D004566:Electrodes / Q000009:adverse effects; D005260:Female; D018756:GABA Antagonists / Q000627:therapeutic use; D006930:Hyperalgesia / Q000503:physiopathology / Q000628:therapy; D007650:Ketanserin / Q000627:therapeutic use; D008784:Methysergide / Q000627:therapeutic use; D009437:Neuralgia / Q000503:physiopathology* / Q000628:therapy*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D010646:Phentolamine / Q000627:therapeutic use; D011433:Propranolol / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012702:Serotonin Antagonists / Q000627:therapeutic use; D013116:Spinal Cord / Q000502:physiology*; D013469:Sulpiride / Q000627:therapeutic use; D013997:Time Factors; D004561:Transcutaneous Electric Nerve Stimulation / Q000379:methods*
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D018492:Dopamine Antagonists; D018756:GABA Antagonists; D012702:Serotonin Antagonists; D013469:Sulpiride; D007650:Ketanserin; D011433:Propranolol; D001418:Baclofen; C080629:saclofen; D008784:Methysergide; D001640:Bicuculline; D010646:Phentolamine