Adrenoreceptor subtype mediating sympathetic-sensory coupling in injured sensory neurons.
1. Teased axon recordings were made from 167 spontaneously active A beta- and A delta-afferents that ended in sciatic nerve end neuromas of 6-12 days standing. When challenged with a standard bolus of systemically applied adrenaline, 100 (60%) responded, either with an increase in baseline firing frequency (excitation, 96/100) or with a decrease (suppression, 4/100). 2. Experiments using receptor type-selective antagonists indicated that the adreno-sensitivity was mediated by alpha 2 adrenoreceptors in 65% of the afferents sampled, by alpha 1 adrenoreceptors in 13%, and about equally by alpha 1 and alpha 2 adrenoreceptors in approximately 10%. In the remaining 13%, neither type of antagonist blocked adrenaline-evoked excitation, at least not at the doses used. Both excitatory and suppressive responses were primarily sensitive to alpha 2 antagonists. 3. Experiments using receptor type-selective agonists substantiated the conclusion that sympathetic-sensory coupling at sites of nerve injury is mediated primarily by alpha 2 adrenoreceptors. 4. Recordings were also made from 14 afferent neurons with spontaneous ectopic discharge originating in dorsal root ganglia (DRGs) L4 and L5. The rats had undergone transection of the ipsilateral sciatic nerve 8-93 days previously. All neurons responded to systemic adrenaline and/or trains of activity evoked in postganglionic sympathetic efferents with either excitation or suppression. As in the neuroma endings, responses in the large majority of cases were blocked by alpha 2-selective, but not by alpha 1-selective adrenoreceptor antagonists. 5. The results indicate that sympathetic-sensory coupling, both at nerve injury sites and in axotomized DRG neurons, is mediated primarily by alpha 2 adrenoreceptors. In a minority of afferent neurons, however, it appears to be mediated by alpha 1 adreno-receptors or by both alpha 1 and alpha 2 adrenoreceptors. These functional results are consistent with receptor-type expression profiles from studies based on in situ hybridization and immunocytochemistry.
Chen
Y
Y
Department of Cell and Animal Biology, Hebrew University of Jerusalem, Israel.
Michaelis
M
M
Janig
W
W
Devor
M
M
D000322:Adrenergic Agonists / Q000494:pharmacology; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000502:physiology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D008297:Male; D009437:Neuralgia / Q000503:physiopathology*; D009463:Neuroma / Q000473:pathology / Q000503:physiopathology; D009475:Neurons, Afferent / Q000502:physiology*; D010524:Peripheral Nervous System Neoplasms / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology*; D012584:Sciatic Nerve / Q000166:cytology / Q000293:injuries*; D013564:Sympathetic Nervous System / Q000502:physiology*
D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D011941:Receptors, Adrenergic