Physiological contributions of neurokinin 1 receptor activation, and interactions with NMDA receptors, to inflammatory evoked spinal c-Fos expression. Chapman, Victoria, Jaroslava Buritova, Prisca Honor[acute]e and Jean-Marie Besson. Physiopharmacologie du Syst[grave]eme Nerveux, INSERM U 161 and EPHE, 2 rue d'Al[acute]esia, 75014 Paris, France.
APStracts 3:0084N, 1996.
SUMMARY AND CONCLUSIONS
1. Intraplantar injection of formalin (5%, 100[mu]l in saline) was associated with a high level of spinal c-Fos immunoreactivity and a peripheral paw and ankle edema, as assessed at 3 hours after formalin administration. For the two experimental series the control number of formalin evoked Fos like immunoreactive (Fos-LI) neurons were 174+/-6 and 193+/-18 Fos-LI neurons per 40[mu]m section of the lumbar segment L4-L5 of the rat spinal cord. For both series of experiments Fos-LI neurons were predominantly located in the superficial (I-II; 40% and 44% of the total number of Fos-LI neurons, for the two experimental series) and deep (V-VI; 37% and 40% of the total number of Fos-LI neurons, for the two experimental series) laminae of the dorsal horn of the spinal cord. The small number of remaining Fos-LI neurons were located in the nucleus proprius (laminae III-IV) and the ventral horn. 2. Prior intravenous administration of RP67580 (0.05, 0.5, 1.5mg/kg), a selective neurokinin 1 (NK1) receptor antagonist, dose-relatedly reduced the total number of formalin evoked Fos-LI neurons (88+/-5%, 80+/-4%, p<0.01 and 64+/- 4%, p<0.0001, of the control number of formalin evoked Fos-LI neurons). Laminar analysis of the regional effect of RP67580 on formalin evoked Fos-LI neurons illustrated that the number of superficial and deep laminae Fos-LI neurons were attenuated to a similar extent by RP67580. 3. Prior intravenous administration of RP68651 (1.5mg/kg), the inactive isomer of RP67580, produced only a small reduction in the total number of formalin evoked Fos-LI neurons (84+/-5% of the control number of formalin evoked Fos-LI neurons, p<0.05). The effect of RP68651 on the number of formalin evoked Fos-LI neurons was significantly smaller (p<0.01) than the effect of the equivalent concentration of RP67580, the active isomer. 4. Prior co-administration of intravenous RP67580 (0.5mg/kg) and subcutaneous (+)-HA966 (2.5mg/kg), an antagonist at the glycine site of the N-methyl-D-aspartate (NMDA) receptor, significantly reduce the number of formalin evoked Fos-LI neurons (64+/-4% of the control number of formalin evoked Fos-LI neurons, p<0.01). The attenuating effect of co- administered RP67580 and (+)-HA966 was significantly greater than the effect of RP67580 alone (p<0.01) and the effect of (+)-HA966 alone (p<0.05). Laminar analysis illustrated that co-administered RP67580 and (+)-HA966 reduced the number of formalin evoked Fos-LI neurons in the superficial and deep laminae to a similar extent. 5. Intraplantar injection of formalin was associated with a peripheral paw (0.92+/-0.02 cm) and ankle (0.92+/-0.02 cm) edema, as compared to the paw (0.46+/-0.02cm) and ankle (0.67+/-0.14cm) diameters of saline stimulated rats. Neither prior administration of intravenous RP67580 (0.05, 0.5, 1.5mg/kg), or RP68651 (1.5mg/kg) or prior co-administration of RP67580 (0.5mg/kg) and (+)-HA966 (2.5mg/kg) influenced the extent of the paw or ankle edema at 3 hours after intraplantar injection of formalin. 6. Our results illustrate that NK1 receptor activation contributes to inflammatory evoked spinal c-Fos expression and thus supports the current contention that NK1 receptor activation, and by inference SP, plays a role in spinal nociceptive processing. The second part of our study suggests that the previously reported NK1/NMDA receptor interactions contribute to formalin evoked spinal c-Fos expression, and consequently may contribute to the longer term spinal neuroplasticity associated with inflammatory nociceptive processing.

Received 7 December 1995; accepted in final form 18 April 1996.
APS Manuscript Number J824-5.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 May 96