Brain microinjection studies in the rat using
local anesthetics suggest that the rostral ventral medulla (RVM) contributes to the facilitation of
neuropathic pain. However, these studies were restricted to a single model of
neuropathic pain (the spinal nerve
ligation model) and to just two stimulus modalities (non-noxious tactile stimulus and heat). Also, few
neurotransmitter systems have been shown to modulate descending facilitation. After either partial sciatic nerve
ligation (PSNL) or spared nerve injury (SNI), we found that unilateral or bilateral microinjection of
lidocaine into the RVM reduced not only
mechanical allodynia (decreased threshold to von Frey hairs and/or an automated device) and
mechanical hyperalgesia (increased paw lifting in response to a noxious pin), but also
cold hypersensitivity (increased lifting in response to the hindpaw application of a drop of
acetone). Application of a drop of water did not elicit paw withdrawal, indicating that the
acetone test is indeed a measure of
cold hypersensitivity. We found significant
neuropeptide Y Y1-like immunoreactivity within, and lateral to, the midline RVM. Intra-RVM injection of
neuropeptide Y (NPY) dose-dependently inhibited the mechanical and
cold hypersensitivity associated with PSNL or SNI, an effect that could be blocked by the Y1 receptor antagonist
BIBO 3304. We conclude that medullary facilitation spans multiple behavioral signs of
allodynia and
hyperalgesia in multiple models of
neuropathic pain. Furthermore, NPY inhibits behavioral signs of
neuropathic pain, possibly by acting at Y1 receptors in the RVM.