title: The midbrain central gray best suppresses chronic pain with electrical stimulation at very low pulse rates in two human cases.
abstract: Deep brain stimulation in the midbrain׳s central gray can relieve neuropathic pain in man, but for unclear reasons sometimes fails intraoperatively or in early weeks. Here we describe continuous bilateral stimulation in the central gray of two subjects with longstanding, severe neuropathic pain from spinal cord injury. Stimulation parameters were recursively adjusted over many weeks to optimize analgesia while minimizing adverse effects. In early weeks, adjustments were made in periodic office visits; subjects later selected ad libitum at home among several blinded choices while rating pain twice daily. Both subjects received significantly better pain relief when stimulus pulse rates were low. The best relief occurred with 2 Hz cycled on for 1s and off for 2s. After inferior parameters were set, pain typically climbed slowly over 1-2 days; superior parameters led to both slow and fast improvements. Over many weeks of stimulation at low pulse rates, both subjects experienced significantly less interference from pain with sleep. One subject, with major pain relief, also showed less interference with social/recreational ability and mood; the other subject, despite minor pain relief, experienced a significantly positive global impression of change. Oscillopsia, the only observed complication of stimulation, disappeared at low mean pulse rates (≤ 3/s). These subjects׳ responses are not likely to be unique even if they are uncommon. Thus daily or more frequent pain assessment, combined with slower periodic adjustment of stimulation parameters that incorporate mean pulse rates about one per second, will likely improve success with this treatment.
authors.affiliation: The Miami Project to Cure Paralysis and Department of Neurological Surgery, Miller School of Medicine, University of Miami, R-48, Miami, FL 33136, USA. Electronic address: ihentall@med.miami.edu.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Hentall
authors.affiliation: The Miami Project to Cure Paralysis and Department of Neurological Surgery, Miller School of Medicine, University of Miami, R-48, Miami, FL 33136, USA.
authors.forename: Corneliu C
authors.initials: CC
authors.lastname: Luca
authors.affiliation: The Miami Project to Cure Paralysis and Department of Neurological Surgery, Miller School of Medicine, University of Miami, R-48, Miami, FL 33136, USA.
authors.forename: Eva
authors.initials: E
authors.lastname: Widerstrom-Noga
authors.affiliation: The Miami Project to Cure Paralysis and Department of Neurological Surgery, Miller School of Medicine, University of Miami, R-48, Miami, FL 33136, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Vitores
authors.affiliation: The Miami Project to Cure Paralysis and Department of Neurological Surgery, Miller School of Medicine, University of Miami, R-48, Miami, FL 33136, USA.
authors.forename: Letitia D
authors.initials: LD
authors.lastname: Fisher
authors.affiliation: The Miami Project to Cure Paralysis and Department of Neurological Surgery, Miller School of Medicine, University of Miami, R-48, Miami, FL 33136, USA; Department of Veterans Affairs Medical Center, Miami, FL 33101, USA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Martinez-Arizala
authors.affiliation: The Miami Project to Cure Paralysis and Department of Neurological Surgery, Miller School of Medicine, University of Miami, R-48, Miami, FL 33136, USA.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Jagid
mesh_terms: D000328:Adult; D002574:Cervical Vertebrae / Q000293:injuries; D059350:Chronic Pain / Q000175:diagnosis* / Q000209:etiology / Q000628:therapy*; D046690:Deep Brain Stimulation / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D059408:Pain Management / Q000379:methods*; D010147:Pain Measurement / Q000379:methods; D010487:Periaqueductal Gray / Q000502:physiology*; D013119:Spinal Cord Injuries / Q000150:complications / Q000175:diagnosis / Q000628:therapy; D013904:Thoracic Vertebrae / Q000293:injuries
keywords: Deep brain stimulation; Neuropathic pain; Periaqueductal gray; Periventricular gray; Spinal cord injury