title: Differential regulation of peripheral IL-1β-induced mechanical allodynia and thermal hyperalgesia in rats.
abstract: This study examined the differential mechanisms of mechanical allodynia and thermal hyperalgesia after injection of interleukin (IL) 1β into the orofacial area of male Sprague-Dawley rats. The subcutaneous administration of IL-1β produced both mechanical allodynia and thermal hyperalgesia. Although a pretreatment with iodoresiniferatoxin (IRTX), a transient receptor potential vanilloid 1 (TRPV1) antagonist, did not affect IL-1β-induced mechanical allodynia, it significantly abolished IL-1β-induced thermal hyperalgesia. On the other hand, a pretreatment with D-AP5, an N-methyl-d-aspartate (NMDA) receptor antagonist, and NBQX, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, blocked IL-1β-induced mechanical allodynia. Pretreatment with H89, a protein kinase A (PKA) inhibitor, blocked IL-1β-induced mechanical allodynia but not thermal hyperalgesia. In contrast, pretreatment with chelerythrine, a protein kinase C (PKC) inhibitor, inhibited IL-1β-induced thermal hyperalgesia. Subcutaneous injections of 2% lidocaine, a local anesthetic agent, blocked IL-1β-induced thermal hyperalgesia but not IL-1β-induced mechanical allodynia. In the resiniferatoxin (RTX)-pretreated rats, a subcutaneous injection of IL-1β did not produce thermal hyperalgesia due to the depletion of TRPV1 in the primary afferent fibers. Double immunofluorescence revealed the colocalization of PKA with neurofilament 200 (NF200) and of PKC with the calcitonin gene-related peptide (CGRP) in the trigeminal ganglion. Furthermore, NMDA receptor 1 (NR1) and TRPV1 predominantly colocalize with PKA and PKC, respectively, in the trigeminal ganglion. These results suggest that IL-1β-induced mechanical allodynia is mediated by sensitized peripheral NMDA/AMPA receptors through PKA-mediated signaling in the large-diameter primary afferent nerve fibers, whereas IL-1β-induced thermal hyperalgesia is mediated by sensitized peripheral TRPV1 receptors through PKC-mediated signaling in the small-diameter primary afferent nerve fibers.
authors.affiliation: Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea Department of Pediatric Dentistry, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea Department of Oral Anatomy, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Min J
authors.initials: MJ
authors.lastname: Kim
authors.forename: Sang Y
authors.initials: SY
authors.lastname: Lee
authors.forename: Kui Y
authors.initials: KY
authors.lastname: Yang
authors.forename: Soon H
authors.initials: SH
authors.lastname: Nam
authors.forename: Hyun J
authors.initials: HJ
authors.lastname: Kim
authors.forename: Young J
authors.initials: YJ
authors.lastname: Kim
authors.forename: Yong C
authors.initials: YC
authors.lastname: Bae
authors.forename: Dong K
authors.initials: DK
authors.lastname: Ahn
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006930:Hyperalgesia / Q000139:chemically induced*; D053583:Interleukin-1beta / Q000633:toxicity*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D017288:Pain Threshold / Q000187:drug effects*; D010812:Physical Stimulation; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000378:metabolism
chemical_list: D004224:Diterpenes; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D053583:Interleukin-1beta; D009419:Nerve Tissue Proteins; D011810:Quinoxalines; C468130:iodoresiniferatoxin; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D015763:2-Amino-5-phosphonovalerate
keywords: Air puff; IL-1β; Mechanical allodynia; NMDA; TRPV1; Thermal hyperalgesia