Abstract
The information of nociceptive stimuli given to the periphery is transmitted through primary-afferent fibers to the spinal dorsal horn, especially substantia gelatinosa (SG; lamina II), which plays a pivotal role in regulating the nociceptive transmission. The SG neurons receive (glutamatergic) excitatory and (GABAergic and glycinergic) inhibitory transmissions in a mono- or poly-synaptic manner through myelinated Aδ and unmyelinated C fibers. Many of extrinsic and intrinsic analgesics inhibit the excitatory transmission and/or enhance the inhibitory transmission, both of which modulations are mediated by G-protein coupled metabotropic neurotransmitter receptors. Monosynaptic Aδ-fiber and C-fiber transmission inhibitions by many analgesics are different in extent from each other. The activation of metabotropic neurotransmitter receptors expressed in postsynaptic SG neurons produces a membrane hyperpolarization. These actions result in a relief of pain sensation. The central terminals of the primary-afferent neurons express transient receptor potential (TRP) channels, the activation of which increases the spontaneous release of L-glutamate to the SG neurons; this may produce a nociception. Nerve conduction in primary-afferent neurons is inhibited by metabotropic neurotransmitter receptor agonists, such as opioids and α2 adrenoceptor agonists, without receptor activation, and also by TRP agonists in a manner independent of the channels. Such a conduction inhibition may produce a local anesthetic effect. It is concluded that nociceptive transmission to the SG from periphery is regulated by modulating synaptic transmission and nerve conduction through an action of metabotropic neurotransmitter receptor and TRP agonists.
