Adrenergic sensitivity of the sensory receptors modulating mechanical allodynia in a rat neuropathic pain model.
This study focuses on changes in adrenergic sensitivity in untransected sensory axons that innervate an area of skin made neuropathic by transection of neighboring nerves. The segmental nerve injury model is favorable for this since all axons in the L5 and L6 nerves are transected whereas the L4 axons are intact. Earlier findings are that pain behaviors develop after this injury and that these behaviors are ameliorated by sympathectomy. The present study shows that behavior indicating mechanical allodynia can be rekindled after sympathectomy by intradermal norepinephrine and alpha-2 but not alpha-1 adrenergic ligands and the rekindling can be blocked by alpha-2 but not alpha-1 adrenergic antagonists. By contrast neither intradermal norepinephrine nor other adrenergic agonists or antagonists have any demonstrable effects in the normal or after either neuropathic surgery or sympathectomy alone. These data suggest that the combination of neuropathic surgery and sympathectomy results in an upregulation of active alpha-2 adrenergic receptors on the undamaged sensory axons that provide the remaining sensory innervation to a neuropathic area partially denervated by segmental nerve lesions. These changes on undamaged axons presumably compliment similar changes on the transected axons and, thus play a role in the development of neuropathic pain.
Moon
Dong Eon
DE
Marine Biomedical Institute, University of Texas Medical Branch, Galveston, TX 77555-1069, USA Departments of Anatomy and Neurosciences, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1069, USA Departments of Physiology and Biophysics, University of Texas Medical Branch, Galveston, TX 77555-1069, USA.
Lee
Doo Hyun
DH
Han
Hee Chul
HC
Xie
Jiangang
J
Coggeshall
Richard E
RE
Chung
Jin Mo
JM
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002422:Causalgia / Q000503:physiopathology*; D003000:Clonidine / Q000494:pharmacology; D019329:Idazoxan / Q000494:pharmacology; D008297:Male; D009475:Neurons, Afferent / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology*; D010656:Phenylephrine / Q000494:pharmacology; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000737:chemistry / Q000166:cytology / Q000503:physiopathology; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000166:cytology / Q000503:physiopathology* / Q000601:surgery; D015016:Yohimbine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D010656:Phenylephrine; D015016:Yohimbine; D003000:Clonidine; D009638:Norepinephrine; D019329:Idazoxan