Substance P and capsaicin-induced mechanical hyperalgesia in the rat knee joint; The involvement of bradykinin B-1 and B-2 receptors

1 Substance P (SP) and capsaicin induced a mechanical hyperalgesia when injected into rat knee joints. 2 The NK1 receptor antagonists CP 99994 (10-100 nmol) and RP 67580 (0.1-1 nmol) blocked the development of, and also reversed, SP-induced hyperalgesia. Capsaicin (10 nmol)-induced hyperalgesia was blocked by capsazepine (0.5-5 nmol). 3 Capsaicin-induced hyperalgesia was prevented and reversed by the NK1 receptor antagonists CP 99994 (100 nmol) and RP 67580 (1 nmol). 4 The bradykinin B-2 receptor antagonist icatibant (5 pmol) blocked the development of both SP and capsaicin-induced hyperalgesia. Icatibant (100 pmol kg(-1), i.v.) also reversed an established SP and capsaicin-induced hyperalgesia. 5 Both low dose SP (1 nmol) and capsaicin (1 nmol)-induced hyperalgesia were potentiated by the kininase II inhibitor captopril (100 mu g). 6 The B-1 receptor antagonists desArg(9)Leu(8)-bradykinin (BK) (0.5-5 nmol) and desArg(10)[Hoe 140](5-50 pmol) only blocked the development of SP-induced hyperalgesia for 30 min after administration. desArg(9)Leu(8)-BK (10 nmol kg(-1) i.v.) did not reverse an established SP-induced hyperalgesia. 7 Capsaicin-induced hyperalgesia was blocked by desArg(9)Leu(8)-BK (0.5 nmol) and this antagonist also reversed an established capsaicin-induced hyperalgesia. 8 Interleukin-1 receptor antagonist (IL-1ra 0.1 mu g) reduced the development of SP-induced hyperalgesia up to 4 h after administration, but did not reverse an established hyperalgesia. IL-1ra (0.1 mu g) also blocked the development of and reversed an established capsaicin-induced hyperalgesia. 9 Indomethacin pretreatment (1 mg kg(-1), s.c.) did not reduce the development of either SP- or capsaicin-induced hyperalgesia but following indomethacin-pretreatment desArg(9)Leu(8)-BK (10 nmol kg(-1), i.v.) failed to reverse a capsaicin-induced hyperalgesia. 10 In conclusion, both SP and capsaicin can induce behavioural hyperalgesia when injected into the knee joint of rats. In addition, blockade of NK1, bradykinin B-1, B-2 and IL-1 beta receptors can substantially modulate this hyperalgesia.