title: Neural correlates of hyperalgesia in the monosodium iodoacetate model of osteoarthritis pain.
abstract: BACKGROUND
  The mechanisms driving osteoarthritic pain remain poorly understood, but there is increasing evidence for a role of the central nervous system in the chronification of pain. We used functional magnetic resonance imaging to investigate the influence of a model of unilateral knee osteoarthritis on nociceptive processing.
  
  
  RESULTS
  Four to five weeks post intra-articular injection of monosodium iodoacetate (MIA, 1 mg) into the left knee, Sprague Dawley rats were anesthetized for functional magnetic resonance imaging studies to characterize the neural response to a noxious stimulus (intra-articular capsaicin injection). In a two-arm cross-over design, 5 µM/50 µl capsaicin was injected into either the left knee (n = 8, CAPS-MIA) or right control knee (n = 8, CAPS-CON), preceded by contralateral vehicle (SAL) injection. To assess neural correlates of mechanical hyperalgesia, hindpaws were stimulated with von Frey hairs (8 g: MIA; 15 g: control knee, based on behavioral withdrawal responses). The CAPS-MIA group exhibited significant activation of the periaqueductal gray, unilateral thalamus and bilateral mensencephalon, superior-colliculus, and hippocampus, with no significant activation in the other groups/conditions. Capsaicin injection increased functional connectivity in the mid-brain network and mediodorsal thalamic nucleus, hippocampus, and globus pallidus, which was significantly stronger in CAPS-MIA compared to CAPS-CON groups. Mechanical stimulation of the hyperalgesic (ipsilateral to MIA knee) and normalgesic (contralateral) hindpaws evoked qualitatively different brain activation with more widespread brainstem and anterior cingulate (ACC) activation when stimulating the hyperalgesic paw, and clearer frontal sensory activation from the normalgesic paw.
  
  
  CONCLUSIONS
  We provide evidence for modulation of nociceptive processing in a chronic knee osteoarthritis pain model with stronger brain activation and alteration of brain networks induced by the pro-nociceptive stimulus. We also report a shift to a medial pain activation pattern following stimulation of the hyperalgesic hindpaw. Taken together, our data support altered neural pain processing as a result of peripheral and central pain sensitization in this model.
authors.affiliation: Radiological Sciences, Division of Clinical Neuroscience, University of Nottingham, Nottingham, UK.
authors.forename: Maryam
authors.initials: M
authors.lastname: Abaei
authors.affiliation: Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK School of Life Sciences, University of Nottingham, Nottingham, UK.
authors.forename: Devi R
authors.initials: DR
authors.lastname: Sagar
authors.affiliation: Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK School of Life Sciences, University of Nottingham, Nottingham, UK.
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Stockley
authors.affiliation: School of Life Sciences, University of Nottingham, Nottingham, UK.
authors.forename: Clare H
authors.initials: CH
authors.lastname: Spicer
authors.affiliation: Medical Imaging Unit, School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Prior
authors.affiliation: Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK School of Life Sciences, University of Nottingham, Nottingham, UK Victoria.chapman@nottingham.ac.uk Dorothee.Auer@nottingham.ac.uk.
authors.forename: Victoria
authors.initials: V
authors.lastname: Chapman
authors.affiliation: Radiological Sciences, Division of Clinical Neuroscience, University of Nottingham, Nottingham, UK Arthritis Research UK Pain Centre, University of Nottingham, Nottingham, UK Medical Imaging Unit, School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: Dorothee P
authors.initials: DP
authors.lastname: Auer
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D001931:Brain Mapping; D002211:Capsaicin; D004195:Disease Models, Animal; D004558:Electric Stimulation; D006930:Hyperalgesia / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007270:Injections, Intra-Articular; D007461:Iodoacetates / Q000494:pharmacology / Q000627:therapeutic use*; D019807:Iodoacetic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D059225:Nociception / Q000187:drug effects; D020370:Osteoarthritis, Knee / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D010146:Pain / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D017207:Rats, Sprague-Dawley
chemical_list: D007461:Iodoacetates; D002211:Capsaicin; D019807:Iodoacetic Acid
keywords: Hyperalgesia; osteoarthritis model; pain fMRI