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 B2 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 micrograms). 6. The B1 receptor antagonists desArg9Leu8-bradykinin (BK) (0.5-5 nmol) and desArg10[
Hoe 140] (5-50 pmol) only blocked the development of SP-induced
hyperalgesia for 30 min after administration. desArg9Leu8-BK (10 nmol kg-1 i.v.) did not reverse an established SP-induced
hyperalgesia. 7.
Capsaicin-induced
hyperalgesia was blocked by desArg9Leu8-BK (0.5 nmol) and this antagonist also reversed an established
capsaicin-induced
hyperalgesia. 8.
Interleukin-1 receptor antagonist (IL-1ra 0.1 microgram) reduced the development of SP-induced
hyperalgesia up to 4 h after administration, but did not reverse an established
hyperalgesia.
IL-1ra (0.1 microgram) 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 desArg9Leu8-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 B1, B2 and
IL-1 beta receptors can substantially modulate this
hyperalgesia.