title: Spinal nociceptive transmission by mechanical stimulation of bone marrow.
abstract: BACKGROUND
  Since bone marrow receives innervation from A-delta and C-fibers and since an increase in intramedullary pressure in bone marrow may induce acute pain in orthopedic patients during surgery and chronic pain in patients with bone marrow edema, skeletal pain may partly originate from bone marrow. Intraosseous lesions, such as osteomyelitis and bone cancer, are also known to produce cutaneous hypersensitivity, which might be referred pain from bone. However, little is known about pain perception in bone marrow and referred pain induced by bone disease. Thus, we carried out an in vivo electrophysiological study and behavioral study to determine whether increased intraosseous pressure of the femur induces acute pain and whether increased intraosseous pressure induces referred pain in the corresponding receptive fields of the skin.
  
  
  RESULTS
  Intraosseous balloon inflation caused spontaneous pain-related behavior and mechanical hyperalgesia and allodynia in the lumbosacral region. Single neuronal activities of spinal dorsal horn neurons were extracellularly isolated, and then evoked responses to non-noxious and noxious cutaneous stimuli and intraosseous balloon inflation were recorded. Ninety-four spinal dorsal horn neurons, which had somatic receptive fields at the lower back and thigh, were obtained. Sixty-two percent of the wide-dynamic-range neurons (24/39) and 86% of the high-threshold neurons (12/14) responded to intraosseous balloon inflation, while none of the low-threshold neurons (0/41) responded to intraosseous balloon inflation. Spinally administered morphine (1 µg) abolished balloon inflation-induced spontaneous pain-related behavior and mechanical hyperalgesia in awake rats and also suppressed evoked activities of wide-dynamic-range neurons to noxious cutaneous stimulation and intraosseous balloon inflation.
  
  
  CONCLUSIONS
  The results suggest that mechanical stimulation to bone marrow produces nociception, concomitantly producing its referred pain in the corresponding skin fields. These mechanisms might contribute to pain caused by skeletal diseases.
authors.affiliation: Department of Anesthesiology and Resuscitology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan tisd@shinshu-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Department of Anesthesiology and Resuscitology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: Department of Anesthesiology and Resuscitology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Takemi
authors.initials: T
authors.lastname: Sekiguchi
authors.affiliation: Department of Anesthesiology and Resuscitology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sugiyama
authors.affiliation: Department of Anesthesiology and Resuscitology, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Mikito
authors.initials: M
authors.lastname: Kawamata
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000473:pathology*; D002404:Catheterization; D005071:Evoked Potentials / Q000187:drug effects; D005269:Femur / Q000473:pathology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000473:pathology; D006930:Hyperalgesia / Q000473:pathology / Q000503:physiopathology; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D059225:Nociception; D010146:Pain / Q000209:etiology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000473:pathology; D017207:Rats, Sprague-Dawley; D012677:Sensation / Q000187:drug effects; D013116:Spinal Cord / Q000473:pathology* / Q000503:physiopathology*; D013314:Stress, Mechanical
chemical_list: D009270:Naloxone; D009020:Morphine
keywords: Skeletal pain; in vivo electrophysiology; referred pain