An NK1 receptor antagonist microinjected into the periaqueductal gray blocks lateral hypothalamic-induced antinociception in rats.

Substantial data are accumulating that implicate the lateral hypothalamus (LH) as part of the descending pain modulatory system. The LH modifies nociception in the spinal cord dorsal horn partly through connections with the periaqueductal gray (PAG), an area known to play a central role in brainstem modulation of nociception. Early work demonstrated a putative substance P connection between the LH and the PAG, but the connection is not fully defined.

Lateral hypothalamic-induced antinociception may be mediated by a substance P connection with the rostral ventromedial medulla.

Stimulation of the lateral hypothalamus (LH) produces antinociception modified by intrathecal serotonergic receptor antagonists. Spinally-projecting serotonergic neurons in the LH have not been identified, suggesting that the LH innervates brainstem serotonergic neurons in the rostral ventromedial medulla (RVM), known to modify nociception in the spinal cord dorsal horn. To determine whether substance P (SP) plays a role in LH-induced antinociception mediated by the RVM, we conducted an anatomical experiment using retrograde tract tracing combined with double label immunocytochemistry and found that neuron profiles immunoreactive for SP in the LH project to the RVM.

The challenge of chronic pain.

Chronic pain is a complex problem with staggering negative health and economic consequences. The complexity of chronic pain is presented within Cervero and Laird's model that describes three phases of pain, including pain without tissue damage, pain with tissue damage and inflammation, and neuropathic pain. The increased afferent input in phases 2 and 3 of chronic pain produces marked changes in primary afferents, dorsal root ganglia, and spinal cord dorsal horn.