Sensitization of rat dorsal horn neurons by NGF-induced subthreshold potentials and low-frequency activation. A study employing intracellular recordings in vivo.
Intramuscular injection of NGF in human subjects has been reported not to elicit pain, whereas 5% NaCl does. On the other hand, NGF injections induce a long-lasting hyperalgesia. In the present study, the possible neuronal basis of these effects was studied at the spinal level. In anesthetized rats, neurons in the segment L4 were recorded intracellularly before (n=65), during (n=15), and after injections of NGF (n=50) as well as during and after 5% NaCl (during: n=12, after: n=39) into the gastrocnemius-soleus (GS) muscle. The neuronal responses to electrical and mechanical stimuli were tested and possible changes caused by the stimulants recorded. Of those neurons that responded to the NGF injections (7 out of 15), the majority exhibited subthreshold excitatory postsynaptic potentials (EPSPs). Only 3 out of 15 neurons reacted with action potentials (APs) at a low frequency. Already 5 to 30 min after NGF injection, some of these neurons showed signs of a sensitization. In comparison to NGF, hypertonic saline i.m. elicited APs at a higher frequency in a larger number of neurons (9 out of 12). One day after NGF i.m., the proportion of dorsal horn neurons responding with APs to electrical stimulation of the GS nerves had increased significantly from 4.6% to 28.0%. Despite the stronger excitatory effect of 5% NaCl, the sensitization of the dorsal horn neurons after hypertonic saline was less than that after NGF (15.3%). Behavioral experiments showed that NGF injections induced stronger mechanical allodynia and hyperalgesia than hypertonic saline i.m. The data demonstrate that low-frequency activation or even subthreshold potentials in dorsal horn neurons evoked by unmyelinated muscle afferents are an effective means of sensitizing these neurons.
Hoheisel
Ulrich
U
Institute of Pharmacology and Toxicology, Charité, Humboldt University, Dorotheenstrasse 94, D-10117 Berlin, Germany.
Unger
Thomas
T
Mense
Siegfried
S
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004558:Electric Stimulation; D004594:Electrophysiology / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology*; D009220:Myositis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000502:physiology; D020932:Nerve Growth Factor / Q000009:adverse effects / Q000378:metabolism*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000009:adverse effects; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D012965:Sodium Chloride; D020932:Nerve Growth Factor