Current evidence suggests an
analgesic role for the spinal cord action of
general anesthetics; however, the cellular population and intracellular mechanisms underlying anti-
visceral pain by
general anesthetics still remain unclear. It is known that visceral nociceptive signals are transmited via post-synaptic dorsal column (PSDC) and spinothalamic tract (STT) neuronal pathways and that the PSDC pathway plays a major role in visceral nociception. Animal studies report that persistent changes including nociception-associated molecular expression (e.g. neurokinin-1 (
NK-1) receptors) and activation of signal transduction cascades (such as the
protein kinase A [PKA]-c-
AMP-responsive
element binding [CREB] cascade)-in spinal PSDC neurons are observed following
visceral pain stimulation. The clinical practice of interruption of the spinal PSDC pathway in patients with
cancer pain further supports a role of this group of neurons in the development and maintenance of
visceral pain. We propose the hypothesis that
general anesthetics might affect critical molecular targets such as NK-1 and
glutamate receptors, as well as intracellular signaling by
CaM kinase II,
protein kinase C (PKC), PKA, and MAP kinase cascades in PSDC neurons, which contribute to the neurotransmission of
visceral pain signaling. This would help elucidate the mechanism of antivisceral nociception by
general anesthetics at the cellular and molecular levels and aid in development of novel therapeutic strategies to improve clinical management of
visceral pain.