title: Dorsal root ganglion stimulation attenuates the BOLD signal response to noxious sensory input in specific brain regions: Insights into a possible mechanism for analgesia.
abstract: Targeted dorsal root ganglion (DRG) electrical stimulation (i.e. ganglionic field stimulation - GFS) is an emerging therapeutic approach to alleviate chronic pain. Here we describe blood oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI) responses to noxious hind-limb stimulation in a rat model that replicates clinical GFS using an electrode implanted adjacent to the DRG. Acute noxious sensory stimulation in the absence of GFS caused robust BOLD fMRI response in brain regions previously associated with sensory and pain-related response, such as primary/secondary somatosensory cortex, retrosplenial granular cortex, thalamus, caudate putamen, nucleus accumbens, globus pallidus, and amygdala. These regions differentially demonstrated either positive or negative correlation to the acute noxious stimulation paradigm, in agreement with previous rat fMRI studies. Therapeutic-level GFS significantly attenuated the global BOLD response to noxious stimulation in these regions. This BOLD signal attenuation persisted for 20minutes after the GFS was discontinued. Control experiments in sham-operated animals showed that the attenuation was not due to the effect of repetitive noxious stimulation. Additional control experiments also revealed minimal BOLD fMRI response to GFS at therapeutic intensity when presented in a standard block-design paradigm. High intensity GFS produced a BOLD signal map similar to acute noxious stimulation when presented in a block-design. These findings are the first to identify the specific brain region responses to neuromodulation at the DRG level and suggest possible mechanisms for GFS-induced treatment of chronic pain.
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA; Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: cpawela@mcw.edu.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Pawela
authors.affiliation: St. Jude Medical, Sunnyvale, CA, USA.
authors.forename: Jeffery M
authors.initials: JM
authors.lastname: Kramer
authors.affiliation: Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Quinn H
authors.initials: QH
authors.lastname: Hogan
mesh_terms: D000698:Analgesia; D000818:Animals; D004599:Electric Stimulation Therapy / Q000379:methods*; D004567:Electrodes, Implanted; D005528:Foot; D005727:Ganglia, Spinal / Q000502:physiology*; D006614:Hindlimb; D008279:Magnetic Resonance Imaging; D008297:Male; D010100:Oxygen / Q000097:blood*; D010146:Pain / Q000503:physiopathology*; D059408:Pain Management; D051381:Rats; D017207:Rats, Sprague-Dawley; D062187:Spinal Cord Stimulation
chemical_list: D010100:Oxygen
keywords: Analgesia; Dorsal root ganglion (DRG); Functional magnetic resonance imaging (fMRI); Neuromodulation; Pain; Spinal cord stimulation