title: Neural correlates of an injury-free model of central sensitization induced by opioid withdrawal in humans.
abstract: Preclinical evidence suggests that opioid withdrawal induces central sensitization (CS) that is maintained by supraspinal contributions from the descending pain modulatory system (DPMS). Here, in healthy human subjects we use functional magnetic resonance imaging to study the supraspinal activity during the withdrawal period of the opioid remifentanil. We used a crossover design and thermal stimuli on uninjured skin to demonstrate opioid withdrawal-induced hyperalgesia (OIH) without a CS-inducing peripheral stimulus. Saline was used in the control arm to account for effects of time. OIH in this injury-free model was observed in a subset of the healthy subjects (responders). Only in these subjects did opioid infusion and withdrawal induce a rise in activity in the mesencephalic-pontine reticular formation (MPRF), an area of the DPMS that has been previously shown to be involved in states of CS in humans, which became significant during the withdrawal phase compared with nonresponders. Paradoxically, this opioid withdrawal-induced rise in MPRF activity shows a significant negative correlation with the behavioral OIH score indicating a predominant inhibitory role of the MPRF in the responders. These data illustrate that in susceptible individuals central mechanisms appear to regulate the expression of OIH in humans in the absence of tissue injury, which might have relevance for functional pain syndromes where a peripheral origin for the pain is difficult to identify.
authors.affiliation: Centre for Functional Magnetic Resonance Imaging of the Brain, Nuffield Department of Clinical Neurosciences, Division of Anaesthetics, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DU, United Kingdom. vishwani@fmrib.ox.ac.uk
authors.forename: Vishvarani
authors.initials: V
authors.lastname: Wanigasekera
authors.forename: Michael C H
authors.initials: MC
authors.lastname: Lee
authors.forename: Richard
authors.initials: R
authors.lastname: Rogers
authors.forename: Philip
authors.initials: P
authors.lastname: Hu
authors.forename: Irene
authors.initials: I
authors.lastname: Tracey
mesh_terms: D001933:Brain Stem / Q000033:anatomy & histology / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D009293:Opioid-Related Disorders / Q000503:physiopathology*; D010148:Intractable Pain / Q000139:chemically induced / Q000503:physiopathology*; D012154:Reticular Formation / Q000033:anatomy & histology / Q000187:drug effects / Q000503:physiopathology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*