Involvement of bradykinin, cytokines, sympathetic amines and prostaglandins in formalin-induced orofacial nociception in rats.
1. This study characterises some of the mechanisms and mediators involved in the orofacial nociception triggered by injection of formalin into the upper lip of the rat, by assessing the influence of various treatments on behavioural nociceptive responses (duration of facial rubbing) elicited either by a low subthreshold (i.e. non-nociceptive; 0.63%) or a higher concentration of the algogen (2.5%). 2. The kininase II inhibitor captopril (5 mg kg(-1), s.c.) and prostaglandin(PG) E(2) (100 ng lip(-1)) potentiated both phases of the response to 0.63% formalin, whereas tumour necrosis factor (TNF alpha; 5 pg lip(-1)), interleukin(IL)-1 beta (0.5 pg lip(-1)), IL-6 (2 ng lip(-1)) and IL-8 (200 pg lip(-1)), or the indirectly acting sympathomimetic drug tyramine (200 microg lip(-1)), each augmented only the second phase of nociception. 3. Conversely, both phases of nociception induced by 2.5% formalin were inhibited by the bradykinin (BK) B(2) receptor antagonist HOE140 (5 microg lip(-1)) or the selective beta(1)-adrenoceptor antagonist atenolol (100 microg lip(-1)). However, the BK B(1) receptor antagonist des-Arg(9)-Leu(8)-BK (1 and 2 microg lip(-1)), antibody and/or antiserum against each of the cytokines, the adrenergic neurone blocker guanethidine (30 mg kg(-1) day(-1), s.c., for 3 days) and the cyclooxygenase(COX)-2 inhibitor celecoxib (50 and 200 microg lip(-1), s.c.; or 1 and 3 mg kg(-1), i.p.) reduced only the second phase of the response. The nonselective COX inhibitor indomethacin and the 5-lipoxygenase activating protein inhibitor MK886 did not change formalin-induced nociception. 4. Our results indicate that BK, TNF-alpha, IL-1 beta, IL-6, IL-8, sympathetic amines and PGs (but not leukotrienes) contribute significantly to formalin-induced orofacial nociception in the rat and the response seems to be more susceptible to inhibition by B(2) receptor antagonist and selective COX-2 inhibitor than by B(1) receptor antagonist or nonselective COX inhibitor.
Department of Pharmacology, Biological Sciences Section, Federal University of Paraná, PO Box 19031, Curitiba, PR, 81540-970, Brazil.
Juliana G
JG
Chichorro
Berenice B
BB
Lorenzetti
Aleksander R
AR
Zampronio
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology; D001262:Atenolol / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001679:Biogenic Amines / Q000502:physiology*; D001920:Bradykinin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D002216:Captopril / Q000494:pharmacology; D000068579:Celecoxib; D016207:Cytokines / Q000737:chemistry / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005157:Facial Pain / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology; D005557:Formaldehyde / Q000008:administration & dosage; D006145:Guanethidine / Q000494:pharmacology; D006614:Hindlimb / Q000187:drug effects / Q000294:innervation; D007213:Indomethacin / Q000494:pharmacology; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000494:pharmacology; D016209:Interleukin-8 / Q000494:pharmacology; D008046:Lip / Q000187:drug effects / Q000294:innervation; D008297:Male; D000077239:Meloxicam; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1 / Q000502:physiology; D043782:Receptor, Bradykinin B2 / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014439:Tyramine / Q000737:chemistry / Q000502:physiology
D001095:Arachidonic Acids; D001679:Biogenic Amines; D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D016207:Cytokines; D015850:Interleukin-6; D016209:Interleukin-8; D011453:Prostaglandins; D011720:Pyrazoles; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D013449:Sulfonamides; D013843:Thiazines; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D005557:Formaldehyde; D001262:Atenolol; C051090:bradykinin, Leu(8)-des-Arg(9)-; C065679:icatibant; D002216:Captopril; D000068579:Celecoxib; D001920:Bradykinin; D000077239:Meloxicam; D014439:Tyramine; D007213:Indomethacin; D006145:Guanethidine