title: Compound action potentials recorded in the human spinal cord during neurostimulation for pain relief.
abstract: Electrical stimulation of the spinal cord provides effective pain relief to hundreds of thousands of chronic neuropathic pain sufferers. The therapy involves implantation of an electrode array into the epidural space of the subject and then stimulation of the dorsal column with electrical pulses. The stimulation depolarises axons and generates propagating action potentials that interfere with the perception of pain. Despite the long-term clinical experience with spinal cord stimulation, the mechanism of action is not understood, and no direct evidence of the properties of neurons being stimulated has been presented. Here we report novel measurements of evoked compound action potentials from the spinal cords of patients undergoing stimulation for pain relief. The results reveal that Aβ sensory nerve fibres are recruited at therapeutic stimulation levels and the Aβ potential amplitude correlates with the degree of coverage of the painful area. Aβ-evoked responses are not measurable below a threshold stimulation level, and their amplitude increases with increasing stimulation current. At high currents, additional late responses are observed. Our results contribute towards efforts to define the mechanism of spinal cord stimulation. The minimally invasive recording technique we have developed provides data previously obtained only through microelectrode techniques in spinal cords of animals. Our observations also allow the development of systems that use neuronal recording in a feedback loop to control neurostimulation on a continuous basis and deliver more effective pain relief. This is one of numerous benefits that in vivo electrophysiological recording can bring to a broad range of neuromodulation therapies.
authors.affiliation: National Information and Communications Technology Australia, Eveleigh, NSW 2015, Australia Graduate School of Biomedical Engineering, University of New South Wales, Kensington, NSW 2052, Australia Pain Management Research Institute and Kolling Institute, University of Sydney at the Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
authors.forename: John L
authors.initials: JL
authors.lastname: Parker
authors.forename: Dean M
authors.initials: DM
authors.lastname: Karantonis
authors.forename: Peter S
authors.initials: PS
authors.lastname: Single
authors.forename: Milan
authors.initials: M
authors.lastname: Obradovic
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cousins
mesh_terms: D000328:Adult; D000368:Aged; D001703:Biophysics; D004599:Electric Stimulation Therapy / Q000379:methods*; D004562:Electrocardiography / Q000379:methods; D004566:Electrodes; D004824:Epidural Space / Q000502:physiology; D005071:Evoked Potentials / Q000502:physiology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009431:Neural Conduction / Q000502:physiology; D009437:Neuralgia / Q000473:pathology* / Q000628:therapy*; D011187:Posture; D011930:Reaction Time; D013116:Spinal Cord / Q000502:physiology*; D013997:Time Factors