title: Spontaneous firing in C-fibers and increased mechanical sensitivity in A-fibers of knee joint-associated mechanoreceptive primary afferent neurones during MIA-induced osteoarthritis in the rat.
abstract: OBJECTIVE
  Osteoarthritis (OA) pain mechanisms are poorly understood. We used the monosodium iodoacetate (MIA) model of knee OA to characterize changes in excitability during the course of OA in different classes of mechanosensitive afferents projecting to joint-associated tissues, and examine whether these afferent responses and pain behavior are correlated.
  
  
  METHODS
  Rats were injected intra-articularly with MIA (1mg in 50 μl). Hind-limb weight bearing was studied 3 (MIA3) and 14 (MIA14) days after MIA, followed by deep anesthesia and teased-nerve-fiber recordings. Spontaneous activity (SA) and mechanically evoked responses of A- and C-mechanosensitive fibers (AM and CM respectively, probably nociceptive) innervating tissues associated with the ipsilateral knee joint were examined.
  
  
  RESULTS
  MIA3 and MIA14 rats exhibited reduced ipsilateral weight bearing. SA (>0.02 impulses/s) occurred in ∼50% of CMs from MIA rats vs 0% in normals. SA firing rates in CMs were significantly higher than normal; decreased weight bearing was correlated with increased CM SA rates. Neither percentages of AMs with SA (20%) nor their firing rates (0-0.01 impulses/s) significantly increased after MIA. In contrast, in MIA rats AMs, but not CMs, exhibited decreased mechanical thresholds and increased firing rates in response to suprathreshold mechanical stimulation.
  
  
  CONCLUSIONS
  These findings of increased SA firing rate in CMs but not AMs and increased mechanical sensitivity of AMs, but not CMs, have not previously been reported. These are two distinct important physiological mechanisms that may underpin spontaneous pain (CMs) and stimulus-evoked pain (AMs) in OA. Our data contribute to a mechanism-based understanding of OA pain.
authors.affiliation: School of Physiology and Pharmacology, Medical Sciences Building, University of Bristol, BS8 1TD, UK.
authors.forename: S
authors.initials: S
authors.lastname: Kelly
authors.forename: J P
authors.initials: JP
authors.lastname: Dunham
authors.forename: F
authors.initials: F
authors.lastname: Murray
authors.forename: S
authors.initials: S
authors.lastname: Read
authors.forename: L F
authors.initials: LF
authors.lastname: Donaldson
authors.forename: S N
authors.initials: SN
authors.lastname: Lawson
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D007461:Iodoacetates; D007596:Joints / Q000294:innervation / Q000473:pathology; D008297:Male; D008465:Mechanoreceptors / Q000502:physiology; D040542:Mechanotransduction, Cellular / Q000502:physiology; D009413:Nerve Fibers, Myelinated / Q000502:physiology*; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology*; D009431:Neural Conduction / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology*; D010003:Osteoarthritis / Q000139:chemically induced / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D010146:Pain / Q000209:etiology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D016474:Weight-Bearing
chemical_list: D007461:Iodoacetates