title: Conformation-dependent effects of VIP on nociception in rats.
abstract: The purpose of this study was to determine whether intrathecal injection of aqueous (random coil) vasoactive intestinal peptide (VIP) and VIP self-associated with sterically stabilized phospholipid micelles (alpha-helix VIP) at the lower lumbar vertebral level modulates foot withdrawal latency to low and high rate noxious radiant skin heating in anesthetized rats. We found that intrathecal random coil VIP evoked a significant bimodal, concentration-dependent response, early potent antinociception followed by hyperalgesia, during exposure to low and high rates of skin heating (P<0.05). Intrathecal alpha-helix VIP elicited a qualitatively similar response to that of random coil VIP except that the rate of decay of antinociception was faster and slower at low and high rates of skin heating, respectively. In addition, a low concentration of alpha-helix VIP evoked a potent late antinociception not observed with random coil VIP. Taken together, these data indicate that VIP modulates somatosensory processing in the lumbosacral spinal cord of rats in a complex fashion, and that this response is dependent, in part, on the conformation of VIP in the vicinity of target cells in the peripheral nervous system.
authors.affiliation: Department of Pharmacology, College of Medicine, University of Illinois at Chicago, 60612, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Yeomans
authors.forename: Hayat
authors.initials: H
authors.lastname: Onyüksel
authors.forename: Sumeet
authors.initials: S
authors.lastname: Dagar
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ikezaki
authors.forename: Ying
authors.initials: Y
authors.lastname: Lu
authors.forename: Israel
authors.initials: I
authors.lastname: Rubinstein
mesh_terms: D000818:Animals; D006801:Humans; D008297:Male; D009479:Neuropeptides / Q000737:chemistry; D010146:Pain / Q000209:etiology*; D017933:Peripheral Nervous System / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011487:Protein Conformation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology; D013696:Temperature; D013997:Time Factors; D014660:Vasoactive Intestinal Peptide / Q000737:chemistry*
chemical_list: D009479:Neuropeptides; D010743:Phospholipids; D014660:Vasoactive Intestinal Peptide