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Abstract
Systemic administration of analgesics can lead to serious adverse side effects compromising
therapeutic benefit in some patients. Information coding pain transmits along an afferent
neuronal network, the first synapses of which reside principally in the spinal cord.
Delivery of compounds to spinal cord, the intended site of action for some analgesics,
is potentially a more efficient and precise method for inhibiting the pain signal.
Activation of specific proteins that reside in spinal neuronal membranes can result
in hyperpolarization of secondary neurons, which can prevent transmission of the pain
signal. This is one of the mechanisms by which opioids induce analgesia. The spinal
cord is enriched in such molecular targets, the activation of which inhibit the transmission
of the pain signal early in the afferent neuronal network. This review describes the
pre-clinical models that enable new target discovery and development of novel analgesics
for site-directed pain management.