title: Formalin- or adjuvant-induced peripheral inflammation increases neurokinin-1 receptor gene expression in the mouse.
abstract: Substance P (SP) has been widely studied as a mediator of nociception. The release of SP from primary afferent neurons is increased during nociception, and SP activates neurokinin-1 (NK-1) receptors in the spinal cord and periphery. Nociception-evoked alterations in NK-1 receptor gene expression have been studied in rat models of persistent pain but have not been characterized in any murine models of peripheral inflammation. This study assessed behavioral responses and NK-1 receptor mRNA gene expression in mice receiving formalin or Freund's complete adjuvant (CFA) as an inflammatory stimulus. Mechanical withdrawal thresholds were measured before injection of formalin or CFA and hind paw licking/biting timed during the late-phase of the formalin response. Two and 24 hours after formalin or CFA injection, mechanical withdrawal thresholds were measured and the mice euthanized. Solution hybridization-nuclease protection assays were used to quantify NK-1 receptor mRNA levels. Results demonstrated that inflamed hind paws were edematous, and the withdrawal thresholds of the inflamed hind paws were significantly lower after formalin or CFA injection. Neurokinin-1 receptor mRNA levels in the ipsilateral dorsal spinal cords of mice were higher at 24 h after formalin injection or 4 days after CFA injection. These results confirm that mice are hyperalgesic at late time points after formalin or adjuvant injection when NK-1 receptor gene expression is elevated in the dorsal spinal cord. This supports the hypothesis that increased NK-1 receptor gene expression contributes to the development and maintenance of a hyperalgesic state.
authors.affiliation: Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160-7417, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Allen
authors.forename: Daniel N
authors.initials: DN
authors.lastname: Cortright
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: McCarson
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D005557:Formaldehyde; D005620:Freund's Adjuvant; D015870:Gene Expression; D006614:Hindlimb; D007249:Inflammation / Q000139:chemically induced* / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D008297:Male; D051379:Mice; D009619:Nociceptors / Q000503:physiopathology; D010146:Pain / Q000523:psychology; D012333:RNA, Messenger / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; D005557:Formaldehyde; D005620:Freund's Adjuvant