Nerve injury can produce
hypersensitivity to noxious and normally innocuous stimulation. Injury-induced central (i.e. spinal) sensitization is thought to arise from enhanced afferent input to the spinal cord and to be critical for expression of behavioral
hypersensitivity. Descending facilitatory influences from the rostral ventromedial medulla have been suggested to also be critical for the maintenance, though not the initiation, of experimental
neuropathic pain. The possibility that descending facilitation from the rostral ventromedial medulla is required for the maintenance of central sensitization was examined by determining whether ablation of
mu-opioid receptor-expressing cells within the rostral ventromedial medulla prevented the enhanced expression of repetitive touch-evoked FOS within the spinal cord of animals with spinal nerve
ligation injury as well as nerve injury-induced behavioral
hypersensitivity. Rats received a single microinjection of vehicle,
saporin,
dermorphin or
dermorphin-saporin into the rostral ventromedial medulla and 28 days later, underwent either
sham or spinal nerve
ligation procedures. Animals receiving rostral ventromedial medulla pretreatment with vehicle,
dermorphin or
saporin that were subjected to spinal nerve
ligation demonstrated both thermal and tactile
hypersensitivity, and showed significantly increased expression of touch-evoked FOS in the dorsal horn ipsilateral to nerve injury compared with
sham-operated controls at days 3, 5 or 10 post-spinal nerve
ligation. In contrast, nerve-injured animals pretreated with
dermorphin-saporin showed enhanced behaviors and touch-evoked FOS expression in the spinal dorsal horn at day 3, but not days 5 and 10, post-spinal nerve
ligation when compared with
sham-operated controls. These results indicate the presence of nerve injury-induced behavioral
hypersensitivity associated with nerve injury-induced central sensitization. Further, the results demonstrate the novel concept that once initiated, maintenance of nerve injury-induced central sensitization in the spinal dorsal horn requires descending
pain facilitation mechanisms arising from the rostral ventromedial medulla.