Spinal fMRI reveals decreased descending inhibition during secondary mechanical hyperalgesia.
Mechanical hyperalgesia is one distressing symptom of neuropathic pain which is explained by central sensitization of the nociceptive system. This sensitization can be induced experimentally with the heat/capsaicin sensitization model. The aim was to investigate and compare spinal and supraspinal activation patterns of identical mechanical stimulation before and after sensitization using functional spinal magnetic resonance imaging (spinal fMRI). Sixteen healthy subjects (6 female, 10 male, mean age 27.2 ± 4.0 years) were investigated with mechanical stimulation of the C6 dermatome of the right forearm during spinal fMRI. Testing was always performed in the area outside of capsaicin application (i.e. area of secondary mechanical hyperalgesia). During slightly noxious mechanical stimulation before sensitization, activity was observed in ipsilateral dorsolateral pontine tegmentum (DLPT) which correlated with activity in ipsilateral spinal cord dorsal gray matter (dGM) suggesting activation of descending nociceptive inhibition. During secondary mechanical hyperalgesia, decreased activity was observed in bilateral DLPT, ipsilateral/midline rostral ventromedial medulla (RVM), and contralateral subnucleus reticularis dorsalis, which correlated with activity in ipsilateral dGM. Comparison of voxel-based activation patterns during mechanical stimulation before/after sensitization showed deactivations in RVM and activations in superficial ipsilateral dGM. This study revealed increased spinal activity and decreased activity in supraspinal centers involved in pain modulation (SRD, RVM, DLPT) during secondary mechanical hyperalgesia suggesting facilitation of nociception via decreased endogenous inhibition. Results should help prioritize approaches for further in vivo studies on pain processing and modulation in humans.
Dept of Neuroradiology, University Hospital of Kiel, Arnold-Heller-Strasse 3, Haus 41, 24105 Kiel, Germany; Dept of Neurology, University Hospital of Kiel, Arnold-Heller-Strasse 3, Haus 41, 24105 Kiel, Germany.
Torge
T
Rempe
Dept of Neuroradiology, University Hospital of Kiel, Arnold-Heller-Strasse 3, Haus 41, 24105 Kiel, Germany.
Stephan
S
Wolff
Dept of Neuroradiology, University Hospital of Kiel, Arnold-Heller-Strasse 3, Haus 41, 24105 Kiel, Germany.
Christian
C
Riedel
Dept of Neurology, University Hospital of Kiel, Arnold-Heller-Strasse 3, Haus 41, 24105 Kiel, Germany; Division of Neurological Pain Research and Therapy, University Hospital of Kiel, Arnold-Heller-Strasse 3, Haus 41, 24105 Kiel, Germany.
Ralf
R
Baron
Centre for Neuroscience Studies, Dept of Diagnostic Radiology, Dept of Physics, 228 Botterell Hall, Queen's University, Kingston, Ontario, Canada.
Patrick W
PW
Stroman
Dept of Neuroradiology, University Hospital of Kiel, Arnold-Heller-Strasse 3, Haus 41, 24105 Kiel, Germany.
Olav
O
Jansen
Dept of Neuroradiology, University Hospital of Kiel, Arnold-Heller-Strasse 3, Haus 41, 24105 Kiel, Germany; Division of Neurological Pain Research and Therapy, University Hospital of Kiel, Arnold-Heller-Strasse 3, Haus 41, 24105 Kiel, Germany.
Janne
J
Gierthmühlen
D000328:Adult; D002211:Capsaicin / Q000008:administration & dosage*; D005260:Female; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000000981:diagnostic imaging / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009437:Neuralgia / Q000000981:diagnostic imaging / Q000503:physiopathology; D065821:Pontine Tegmentum / Q000000981:diagnostic imaging / Q000503:physiopathology; D011859:Radiography; D013116:Spinal Cord / Q000000981:diagnostic imaging / Q000503:physiopathology
D002211:Capsaicin