The critical role of leukotriene B₄ in antigen‐induced mechanical hyperalgesia in immunised rats

Abstract

1 We investigated the mediators responsible for mechanical hypersensitivity induced by antigen challenge in rats immunised with ovalbumin (OVA). 2 Challenge with OVA (12.5 -100 mg, intraplantar) caused a dose-and time-dependent mechanical hypersensitivity, which peaked 3 h after, decreased thereafter and reached control levels 24 h later. 3 Levels of TNFa, IL-1b and cytokine-induced neutrophil chemoattractant 1 (CINC-1) were increased in paw skin after antigen challenge. 4 OVA-evoked hypersensitivity was partially inhibited (about 51%) by pretreatment with antiTNFa , IL-1b and IL-8 sera or with IL-1 receptor antagonist (IL-1ra), but not anti-NGF serum. Pretreatment with thalidomide (45 mg kg À1 ) or pentoxifylline (100 mg kg À1 ) also partially inhibited the hypersensitivity at 1 -3 h after challenge. 5 Pretreatment with indomethacin (5 mg kg À1 ) or atenolol (1 mg kg À1 ) reduced the OVA-induced hypersensitivity at 1 and 3 h, but not at 5 h after challenge, while the combination of B 1 and B 2 bradykinin receptor antagonists was ineffective over the same times. 6 Pretreatment with MK886 (5-lipoxygenase-activating protein inhibitor, 3 mg kg À1 ), CP 105696 (LTB 4 receptor antagonist; 3 mg kg À1 ) or dexamethasone (0.5 mg kg À1 ) inhibited the hypersensitivity from 1 to 5 h. Furthermore, LTB 4 levels were increased in the paw skin of challenged rats. 7 In conclusion, our results suggest that the TNFa-, IL-1b-and CINC-1-driven release of prostaglandins, sympathetic amines and LTB 4 mediates the first 3 h of mechanical hypersensitivity induced by antigen challenge in rats. At 5 h after OVA administration, although TNFa has some role, LTB 4 is the critical nociceptive mediator.

Anti-allergic effects of natural tetranortriterpenoids isolated from Carapa guianensis Aublet on allergen-induced vascular permeability and hyperalgesia

“…In addition, the thermal hyperalgesia in response to i. pl. OVA was prevented by nonselective cyclooxygenase blocker diclofenac, a finding similar to the blockade by indomethacin of mechanical hyperalgesia induced by allergen reported by Cunha and coworkers [47]. The present demonstration that prior treatment with TNTP from C. guianensis seed oil, like the glucocorticoid dexamethasone, markedly attenuated the production of PGE 2 in the pleural cavity triggered by OVA strongly suggests that the anti-allergic effects of these compounds could be related to blockade of eicosanoid generation.…”

Ingenuity Network-Assisted Transcription Profiling: Identification of a New Pharmacologic Mechanism for MK886

“…pathway 7 regulating chemotaxis (1), blood coagulation (2), inflammation (3), pain sensation (4), and blood pressure (5). It is also known to stimulate cancer growth (6 -8).…”

Cytokine inhibitors and pain control

“…Th1 immune inflammatory responses are involved in the development of different diseases including rheumatoid arthritis, myocarditis, encephalomyelitis, diabetes, and lupus (69)(70)(71)(72) . Indeed, these inflammatory diseases are frequently accompanied by hyperalgesia.…”