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Substance P and capsaicin‐induced mechanical hyperalgesia in the rat knee joint; the involvement of bradykinin B 1 and B 2 receptors
Author(s) -
Davis A.J.,
Perkins M.N.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15664.x
Subject(s) - hyperalgesia , capsaicin , icatibant , bradykinin , capsazepine , chemistry , receptor antagonist , substance p , pharmacology , antagonist , endocrinology , medicine , receptor , trpv1 , neuropeptide , nociception , biochemistry , transient receptor potential channel
1 Substance P (SP) and capsaicin induced a mechanical hyperalgesia when injected into rat knee joints. 2 The NK 1 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 NK 1 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 μg). 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 μg) reduced the development of SP‐induced hyperalgesia up to 4 h after administration, but did not reverse an established hyperalgesia. IL‐1ra (0.1 μg) 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 NK 1 , bradykinin B 1 , B 2 and IL‐1β receptors can substantially modulate this hyperalgesia.