Differential roles of spinal neurokinin 1/2 receptors in development of persistent spontaneous nociception and hyperalgesia induced by subcutaneous bee venom injection in the conscious rat

To evaluate the roles of spinal neurokinin receptors in the development of persistent nociception and hyperalgesia to thermal and mechanical stimuli i nduced by subcutaneous (s.c.) bee venom injection, effects of intrathecal ( i.t.) pre- or post-treatment with a non-selective antagonist of (NK1/2) rec eptors, [D-Arg1,D-Trp7,9,Leu11] substance P (spantide), and a selective NK3 receptor antagonist, (S)-(N)-(1-(3-(1-benzoyl-3-(3,4-dichlorophenyl)piperi din-3-yl)propyl)-4-phenylpiperidin acetamide (SR142801) were assessed in co nscious rat. Injection of bee venom s.c. into the plantar surface of one hi nd paw resulted in a pathological pain phenomenon characterized by a 1-2 h single phase of persistent spontaneous nociceptive behaviors (continuously flinching the injected paw) and a 72-96h profound primary thermal and mecha nical hyperalgesia in the injection site and a secondary thermal hyperalges ia in the non-injected hindpaw. Pre-treatment with spantide i.t. at 0.05 mu g, 0.5 mug and 5 mug produced a dose-related suppression of the bee venom-i nduced flinching reflex during the whole time course and the inhibitory rat e was 24 +/- 12.60% (35.38 +/- 4.12 flinches/5min, n=5), 48 +/- 6.75% (24.5 3 +/- 2.90 flinches/5min, n =5) and 60 +/- 7.69% (18.88 +/- 3.58 ftinches/5 min, n =5) respectively when compared with the saline control group (46.80 +/- 2.60 flinches) 5 min, n =5). Post-treatment of spantide i.t. at the hi ghest dose (5 mug) used in the present study 5 min after bee venom injectio n also produced a 49% suppression of the flinching reflex in the control gr oup [post-spantide vs saline: 19.42 +/- 3.15 (n=5) vs 38.42 +/- 3.25 flinch es/5min (n=5)]. Moreover, i.t. pre-treatment with 5 mug spantide partially prevented the primary and secondary thermal hyperalgesia from occurring, wh ile it did not show any influence on the development of primary mechanical hyperalgesia. Neither the established thermal nor mechanical hyperalgesia i dentified in the above sites was affected by i.t. post-treatment with the s ame dose of spantide 3h after bee venom injection. Pre and post-treatment o f SR142801 did not produce any significant effect on the bee venom-induced spontaneous pain and thermal and mechanical hyperalgesia. Our present resul t suggests that activation of spinal NK1/2 receptors is involved in both in duction and maintenance of the persistent spontaneous nociception, while it is only involved in induction of the primary and secondary thermal, but no t primary mechanical hyperalgesia induced by s.c. bee venom injection. The spinal NK3 receptor seems not likely to be involved in the bee venom-induce d behavioral response characterized by spontaneous pain and thermal and mec hanical hyperalgesia. (C) 2001 Harcourt Publishers Ltd.