Synaptic plasticity in pathological pain

•Synapses in nociceptive pathways adapt strength in an activity-dependent manner. •Synaptic plasticity in nociceptive pathways is both functional and structural. •We review the molecular mechanisms of synaptic plasticity in nociceptive pathways. •Both pre- and post-synaptic mechanisms are involved in spinal synaptic plasticity. Chronic pain represents a major challenge to clinical practice and basic science. Excitatory neurotransmission in somatosensory nociceptive pathways is predominantly mediated by glutamatergic synapses. A key feature of these synapses is their ability to adapt synaptic strength in an activity-dependent manner. Such disease-induced synaptic plasticity is paramount to alterations in synaptic function and structure. Recent work has recognized that synaptic plasticity at both excitatory and inhibitory synapses can function as a prime mechanism underlying pathological pain. In this review, cellular and molecular mechanisms underlying synaptic plasticity in nociceptive pathways will be reviewed and discussed. New insights derived from these advances are expected to expedite development of novel interventional approaches for treatment of pathological pain. Chronic pain represents a major challenge to clinical practice and basic science. Excitatory neurotransmission in somatosensory nociceptive pathways is predominantly mediated by glutamatergic synapses. A key feature of these synapses is their ability to adapt synaptic strength in an activity-dependent manner. Such disease-induced synaptic plasticity is paramount to alterations in synaptic function and structure. Recent work has recognized that synaptic plasticity at both excitatory and inhibitory synapses can function as a prime mechanism underlying pathological pain. In this review, cellular and molecular mechanisms underlying synaptic plasticity in nociceptive pathways will be reviewed and discussed. New insights derived from these advances are expected to expedite development of novel interventional approaches for treatment of pathological pain. LTP occurs in two phases. Early-phase LTP is independent on de novo protein synthesis and lasts for up to 2–3 hours. Late-phase LTP involves protein synthesis and lasts longer than 3 hours, up to the life span of an animal and may be accompanied by structural changes at synapses. a long-lasting decrease of the response of a postsynaptic nerve cell to stimulation across the synapse that occurs with repeated stimulation, which lasts for an extended period of time (tens of minutes to hours in vitro and hours to days and months or even years in vivo). LTD is a form of long-term synaptic plasticity. a long-lasting strengthening of the response of a postsynaptic nerve cell to stimulation across the synapse that occurs with repeated stimulation, which lasts for an extended period of time (tens of minutes to hours in vitro and hours to days and months or even years in vivo). LTP is a form of long-term synaptic plasticity. long-lasting changes in the efficacy of synaptic connections, which lasts over tens of minutes (e.g., >30 min), hours, months or even years. a phenomenon in which postsynaptic potentials or currents (PSPs, PSCs) evoked by an impulse are decreased when that impulse closely follows a prior impulse. PPD is a form of short-term synaptic plasticity. a phenomenon in which postsynaptic potentials or currents (PSPs, PSCs) evoked by an impulse are increased when that impulse closely follows a prior impulse. PPF is a form of short-term synaptic plasticity. a short-term decrease in synaptic strength under repetitive stimuli within a timescale of milliseconds to seconds. a short-term increase in synaptic strength under repetitive stimuli within a time scale of milliseconds to seconds. a phenomenon in which synaptic efficacy changes over milliseconds to minutes in a way that reflects the history of presynaptic activity. synaptic contacts between two neurons where a presynaptic action potential fails to evoke a detectable postsynaptic signal. A synapse can be presynaptically silent or postsynaptically silent. a conversion of silent synapses to functional synapses. a progessive increase in the magnitude of C-fiber-evoked responses of spinal dorsal horn neurons produced by low-frequency, repetitive stimulation of C fibers.