DIFFERENTIAL ROLES OF NEUROKININ-1 AND NEUROKININ-2 RECEPTORS IN THE DEVELOPMENT AND MAINTENANCE OF HEAT HYPERALGESIA INDUCED BY ACUTE-INFLAMMATION

1 Following induction of acute inflammation by intraarticular injectio n of kaolin and carrageenan into the knee joint in rats, there was a s ignificant decrease in the withdrawal latency to radiant heat applied to the paw (i.e. heat hyperalgesia), an increased joint circumference and increased joint temperature.2 A neurokinin, (NK1) receptor antagon ist (CP-99,994, 10 mM) had no effect on the paw withdrawal latency whe n it was administered spinally through a microdialysis fibre before th e induction of inflammation. Pretreatment with a NK2 receptor antagoni st (SR48968, 1 mM) administered spinally through the microdialysis fib re prevented the heat hyperalgesia from developing in the early stages of the inflammation. 3 Post-treatment through the microdialysis fibre with the NK1 receptor antagonist (0.01-10 mM) was effective in revers ing the heat hyperalgesia. In contrast, post-treatment spinally with t he NK2 receptor antagonist (0.01-1 mM) had no effect on the heat hyper algesia. The inactive stereoisomers of the NK1 receptor antagonist, CP 100,263, or the NK2 receptor antagonist, SR48965, administered at the same doses, had no effect on the joint inflammation or the heat hypera lgesia. 4 Pretreatment systemically with the NK1 receptor antagonist ( 30 mg kg(-1)) had no effect on the heat hyperalgesia or pain-related b ehaviour ratings where 0 is none and 5 is non weight bearing and compl ete avoidance of limb contact. Pretreatment with a NK2 receptor antago nist (10 mg kg(-1)) systemically prevented the heat hyperalgesia and p ain-related behaviour ratings from developing in the early stages of t he inflammation. The inactive stereoisomers of NK1 receptor antagonist , CP100,263, or the NK2 receptor antagonist, SR48965, administered at the same doses, had no effect on the joint inflammation or the heat hy peralgesia. 5 Post-treatment systemically with either the NK1 (0.1-30 mg kg(-1)) or the NK2 (0.1-10 mg kg(-1)) receptor antagonist resulted in a dose-dependent reversal of the heat hyperalgesia. Pain-related be haviour ratings were reduced by post-treatment only with the NK1 recep tor antagonist. The inactive stereoisomers of the NK1 receptor antagon ist, CP100,263, or the NK2 receptor antagonist, SR48965, administered at the same doses, had no effect on the behavioural responses. 6 Direc t pretreatment of the knee joint with either the NK1 (30 mg) or the NK 2 (10 mg) receptor antagonist prevented the heat hyperalgesia from dev eloping without affecting joint swelling. The inactive stereoisomers o f the NK1 receptor antagonist, CP100,263, or the NK2 receptor antagoni st, SR48965, administered at the same doses, had no effect on the join t inflammation or the heat hyperalgesia. 7 There appears to be a diffe rential role for the spinal tachykinin receptors in the development an d maintenance of the heat hyperalgesia associated with acute joint inf lammation. The NK2 receptors appear to be activated early in the devel opment of the heat hyperalgesia and NK1 receptors are involved in the maintenance of the heat hyperalgesia. 8 Peripherally, both NK1 and NK2 receptors are involved in the development of heat hyperalgesia and pa in-related behaviour ratings induced by acute inflammation.