title: fMRI of pain processing in the brain: a within-animal comparative study of BOLD vs. CBV and noxious electrical vs. noxious mechanical stimulation in rat.
abstract: This study aims to identify fMRI signatures of nociceptive processing in whole brain of anesthetized rats during noxious electrical stimulation (NES) and noxious mechanical stimulation (NMS) of paw. Activation patterns for NES were mapped with blood oxygen level dependent (BOLD) and cerebral blood volume (CBV) fMRI, respectively, to investigate the spatially-dependent hemodynamic responses during nociception processing. A systematic evaluation of fMRI responses to varying frequencies of electrical stimulus was carried out to optimize the NES protocol. Both BOLD and CBV fMRI showed widespread activations, but with different spatial characteristics. While BOLD and CBV showed well-localized activations in ipsilateral dorsal column nucleus, contralateral primary somatosensory cortex (S1), and bilateral caudate putamen (CPu), CBV fMRI showed additional bilateral activations in the regions of pons, midbrain and thalamus compared to BOLD fMRI. CBV fMRI that offers higher sensitivity compared to BOLD was then used to compare the nociception processing during NES and NMS in the same animal. The activations in most regions were similar. In the medulla, however, NES induced a robust activation in the ipsilateral dorsal column nucleus while NMS showed no activation. This study demonstrates that (1) the hemodynamic response to nociception is spatial-dependent; (2) the widespread activations during nociception in CBV fMRI are similar to what have been observed in (14)C-2-deoxyglucose (2DG) autoradiography and PET; (3) the bilateral activations in the brain originate from the divergence of neural responses at supraspinal level; and (4) the similarity of activation patterns suggests that nociceptive processing in rats is similar during NES and NMS.
authors.affiliation: Imaging Department, Merck Research Laboratories, West Point, PA 19486, USA. fuqiang_zhao@merck.com
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Zhao
authors.forename: Denise
authors.initials: D
authors.lastname: Welsh
authors.forename: Mangay
authors.initials: M
authors.lastname: Williams
authors.forename: Alexandre
authors.initials: A
authors.lastname: Coimbra
authors.forename: Mark O
authors.initials: MO
authors.lastname: Urban
authors.forename: Richard
authors.initials: R
authors.lastname: Hargreaves
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Evelhoch
authors.forename: Donald S
authors.initials: DS
authors.lastname: Williams
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity; D001810:Blood Volume; D001921:Brain / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D004558:Electric Stimulation; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009415:Nerve Net / Q000503:physiopathology*; D010146:Pain / Q000503:physiopathology*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity