title: Endothelin-1 induced desensitization in primary afferent neurons.
abstract: Endothelin-1 (ET-1) is a known algogen that causes acute pain and sensitization in humans and spontaneous nociceptive behaviors when injected into the periphery in rats, and is elevated during vaso-occlusive episodes (VOEs) in sickle cell disease (SCD) patients. Previously, our lab has shown that a priming dose of ET-1 produces sensitization to capsaicin-induce secondary hyperalgesia. The goal of this study was to determine if the sensitization induced by ET-1 priming is occurring at the level of the primary afferent neuron. Calcium imaging in cultured dorsal root ganglion (DRG) neurons was utilized to examine the effects of ET-1 on primary afferent neurons. ET-1 induces [Ca(2+)]i transients in unprimed cells. ET-1 induced [Ca(2+)]i transients are attenuated by priming with ET-1. This priming effect occurs whether the priming dose is given 0-4 days prior to the challenge dose. Similarly, ET-1 priming decreases capsaicin-induced [Ca(2+)]i transients. At the level of the primary afferent neuron, ET-1 priming has a desensitizing effect on challenge exposures to ET-1 and capsaicin.
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, University of South Carolina, Columbia, SC, United States. Electronic address: Terika.Smith@uscmed.sc.edu.
authors.forename: Terika P
authors.initials: TP
authors.lastname: Smith
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, University of South Carolina, Columbia, SC, United States.
authors.forename: Sherika N
authors.initials: SN
authors.lastname: Smith
authors.affiliation: Department of Pharmacology, Physiology and Neuroscience, University of South Carolina, Columbia, SC, United States; College of Health and Human Services, Concordia University, Portland, OR, United States.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Sweitzer
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000166:cytology; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D061251:Primary Cell Culture; D017207:Rats, Sprague-Dawley; D018689:Sensory System Agents / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D018689:Sensory System Agents; D002211:Capsaicin; D002118:Calcium
keywords: Calcium transients; Capsaicin; Dorsal root ganglia; Endothelin-1(ET-1)