title: Nuclear factor-kappa B regulates pain and COMT expression in a rodent model of inflammation.
abstract: Nuclear factor-kappa B (NF-κB) is a ubiquitously expressed protein complex regulating the transcription of genes involved in inflammation and pain. Increased NF-κB activity in immune and nervous system cells is linked to several chronic pain conditions in humans as well as inflammation and nerve injury-evoked pain in animals. A recent in vitro study further demonstrates that increased NF-κB activity in astrocytes decreases transcription of catechol-o-methyltransferase (COMT), an enzyme that inactivates catecholamines that cause pain. The purpose of the present study was to examine the relationship between systemic and astrocytic NF-κB activity, pain, and COMT expression in an animal model of inflammation. Results demonstrated that administration of the inflammatory stimulant complete Freund's adjuvant (CFA) led to increased pain and decreased COMT protein expression in an NF-κB-dependent manner. Specifically, we found that rats and mice receiving intraplantar CFA exhibited increased behavioral responses to mechanical and thermal heat stimuli. CFA-evoked pain was blocked in rats receiving a pre-emptive systemic dose of the NF-κB inhibitor MG132 and exacerbated in IKKca mice with constitutive NF-κB activity in astrocytes. Furthermore, we observed NF-κB-linked reductions in COMT expression in midbrain at 6h and 1d following CFA in rats and at 1h and 1d in forebrain and midbrain following CFA in IKKca mice. Collectively, these results demonstrate that systemic and astrocytic NF-κB activity drive inflammatory pain and regulate the expression of COMT in forebrain and midbrain structures.
authors.affiliation: Center for Pain Research and Innovation, University of North Carolina, Chapel Hill, NC, USA. Electronic address: Hartung@unc.edu.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Hartung
authors.affiliation: Center for Pain Research and Innovation, University of North Carolina, Chapel Hill, NC, USA. Electronic address: oeskew@live.unc.edu.
authors.forename: Olivia
authors.initials: O
authors.lastname: Eskew
authors.affiliation: Center for Pain Research and Innovation, University of North Carolina, Chapel Hill, NC, USA. Electronic address: terrence_wong@med.unc.edu.
authors.forename: Terrence
authors.initials: T
authors.lastname: Wong
authors.affiliation: Center for Pain Research and Innovation, University of North Carolina, Chapel Hill, NC, USA. Electronic address: inna_tchivileva@unc.edu.
authors.forename: Inna E
authors.initials: IE
authors.lastname: Tchivileva
authors.affiliation: Center for Pain Research and Innovation, University of North Carolina, Chapel Hill, NC, USA. Electronic address: folabomi_oladosu@unc.edu.
authors.forename: Folabomi A
authors.initials: FA
authors.lastname: Oladosu
authors.affiliation: Center for Pain Research and Innovation, University of North Carolina, Chapel Hill, NC, USA. Electronic address: Sandra_obuckley@unc.edu.
authors.forename: Sandra C
authors.initials: SC
authors.lastname: O'Buckley
authors.affiliation: Center for Pain Research and Innovation, University of North Carolina, Chapel Hill, NC, USA. Electronic address: anackley@unc.edu.
authors.forename: Andrea G
authors.initials: AG
authors.lastname: Nackley
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002394:Catechol O-Methyltransferase / Q000378:metabolism*; D004195:Disease Models, Animal; D005620:Freund's Adjuvant; D006358:Hot Temperature; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010146:Pain / Q000209:etiology / Q000378:metabolism*; D010147:Pain Measurement; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007976:Leupeptins; D016328:NF-kappa B; D005620:Freund's Adjuvant; D002394:Catechol O-Methyltransferase; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde
keywords: Astrocytes; Catecholamines; Complete Freund’s adjuvant (CFA); MG132; Tumor necrosis factor-α (TNFα)