title: Pharmacological modulation of pain-related brain activity during normal and central sensitization states in humans.
abstract: Abnormal processing of somatosensory inputs in the central nervous system (central sensitization) is the mechanism accounting for the enhanced pain sensitivity in the skin surrounding tissue injury (secondary hyperalgesia). Secondary hyperalgesia shares clinical characteristics with neurogenic hyperalgesia in patients with neuropathic pain. Abnormal brain responses to somatosensory stimuli have been found in patients with hyperalgesia as well as in normal subjects during experimental central sensitization. The aim of this study was to assess the effects of gabapentin, a drug effective in neuropathic pain patients, on brain processing of nociceptive information in normal and central sensitization states. Using functional magnetic resonance imaging (fMRI) in normal volunteers, we studied the gabapentin-induced modulation of brain activity in response to nociceptive mechanical stimulation of normal skin and capsaicin-induced secondary hyperalgesia. The dose of gabapentin was 1,800 mg per os, in a single administration. We found that (i) gabapentin reduced the activations in the bilateral operculoinsular cortex, independently of the presence of central sensitization; (ii) gabapentin reduced the activation in the brainstem, only during central sensitization; (iii) gabapentin suppressed stimulus-induced deactivations, only during central sensitization; this effect was more robust than the effect on brain activation. The observed drug-induced effects were not due to changes in the baseline fMRI signal. These findings indicate that gabapentin has a measurable antinociceptive effect and a stronger antihyperalgesic effect most evident in the brain areas undergoing deactivation, thus supporting the concept that gabapentin is more effective in modulating nociceptive transmission when central sensitization is present.
authors.affiliation: Department of Human Anatomy and Genetics, and Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, UK. iannetti@fmrib.ox.ac.uk
authors.forename: G D
authors.initials: GD
authors.lastname: Iannetti
authors.forename: L
authors.initials: L
authors.lastname: Zambreanu
authors.forename: R G
authors.initials: RG
authors.lastname: Wise
authors.forename: T J
authors.initials: TJ
authors.lastname: Buchanan
authors.forename: J P
authors.initials: JP
authors.lastname: Huggins
authors.forename: T S
authors.initials: TS
authors.lastname: Smart
authors.forename: W
authors.initials: W
authors.lastname: Vennart
authors.forename: I
authors.initials: I
authors.lastname: Tracey
mesh_terms: D000328:Adult; D000588:Amines / Q000097:blood / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000704:Analysis of Variance; D002211:Capsaicin / Q000633:toxicity; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology*; D018592:Cross-Over Studies; D003509:Cyclohexanecarboxylic Acids / Q000097:blood / Q000494:pharmacology*; D000077206:Gabapentin; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D010146:Pain / Q000503:physiopathology*; D011601:Psychophysics; D005680:gamma-Aminobutyric Acid / Q000097:blood / Q000494:pharmacology*
chemical_list: D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D002211:Capsaicin