Contralateral paw sensitization following injection of endothelin-1: effects of local anesthetics differentiate peripheral and central processes.
Subcutaneous injection of the peptide endothelin-1 (ET-1) into the rat's footpad is known to cause rapid, transient ipsilateral mechanical and thermal sensitization and nocifensive hind paw flinching. Here we report that local injection of ET-1 (2 nmoles) into one hind paw slowly sensitizes the contralateral paw to chemical and mechanical stimulation. There was a 1.5-2-fold increase in the hind paw flinching response, over that from the first injection, to a second injection of the same dose of ET-1 delivered 24 h later into the contralateral paw. A similar increase in the number of flinches during the second phase of the response to formalin also occurred in the contralateral paw 24 h after ET-1. The contralateral paw withdrawal threshold to von Frey hairs was lowered by approximately 55% at 24 h after ipsilateral ET-1 injection. ET-1 injected s.c. at a segmentally unrelated location, the nuchal midline, caused no sensitization of the paws, obviating a systemic route of action. Local anesthetic block of the ipsilateral sciatic nerve during the period of initial response to ipsilateral ET-1 prevented contralateral sensitization, indicating the importance of local afferent transmission, although ipsilateral desensitization was not changed. These findings suggest that peripheral ET-1 actions lead to central sensitization that alters responses to selected stimuli.
Khodorova
A
A
Department of Anesthesiology, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115-6110, USA.
Strichartz
G R
GR
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000503:physiopathology*; D019332:Endothelin-1; D005528:Foot / Q000503:physiopathology; D005557:Formaldehyde; D007839:Functional Laterality; D006614:Hindlimb / Q000503:physiopathology; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010525:Peripheral Nerves / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000503:physiopathology; D013116:Spinal Cord / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D000779:Anesthetics, Local; D019332:Endothelin-1; D005557:Formaldehyde