Involvement of excitatory amino acid receptors and nitric oxide in the rostral ventromedial medulla in modulating secondary hyperalgesia produced by mustard oil

We have recently reported a model of secondary hyperalgesia in which facili tation of the thermal nociceptive tail-flick reflex following topical musta rd oil is largely dependent on descending influences from the rostral ventr omedial medulla (RVM). The current study was designed to examine a potentia l role for excitatory amino acid receptors and nitric oxide in the RVM in m odulating this hyperalgesia. Topical application of mustard oil (100%) to t he lateral surface of the hind leg of awake rats produced a short-lived (60 min) facilitation of the tail-flick reflex that was dose-dependently atten uated by microinjection of the selective N-methyl-D-aspartate (NMDA) recept or antagonist APV (1-100 fmol) into the RVM. Microinjection of a greater do se of APV (1000 fmol) into the RVM produced a significant inhibition of the tail-flick reflex in the presence, but not absence, of mustard oil. In con trast, microinjection of the non-NMDA receptor antagonist DNQX (10 nmol) in to the RVM further enhanced the magnitude and duration of the hyperalgesic response, and produced a facilitation of the tail-flick reflex following in jection into the RVM of naive animals. Similar to APV, microinjection of th e nitric oxide synthase inhibitor L-NAME (100-1000 nmol) into the RVM atten uated mustard oil hyperalgesia, while the greatest dose (1000 nmol) produce d a significant inhibition of the tail-flick reflex in the presence, but no t absence, of mustard oil. A role for nitric oxide synthase in the RVM in m ustard oil hyperalgesia was further demonstrated by a significant increase in the number of NADPH-d labeled cells in the RVM at the time of maximal hy peralgesia. Involvement of NMDA receptors and nitric oxide in the RVM in de scending nociceptive facilitation was supported by the observation that mic roinjection of either NMDA or the NO. donor GEA 5024 into the RVM of naive animals dose-dependently facilitated the tail-flick reflex. The hyperalgesi a produced by NMDA injection into the RVM was blocked by prior intra-RVM in jection of either APV or L-NAME. These results support the notion that seco ndary hyperalgesia produced by mustard oil involves concurrent activation o f dominant descending facilitatory, as well as masked inhibitory systems fr om the RVM. Additionally, the data suggest that descending facilitation inv olves activation of NMDA receptors and production NO. in the RVM, whereas i nhibition involves activation of non-NMDA receptors in the RVM. (C) 1999 In ternational Association for the Study of Pain. Published by Elsevier Scienc e B.V.