Long-term potentiation in spinothalamic neurons.
Sensitization of nociceptive dorsal horn neurons, including spinothalamic tract (STT) cells, is thought to underlie the development of secondary hyperalgesia and allodynia following tissue injury. In central sensitization, responses to stimulation of sensory receptors are enhanced without any change in the excitability of the primary afferent neurons. We hypothesize that central sensitization of STT neurons is a variety of long-term potentiation (LTP). Evidence that LTP occurs in the spinal cord is reviewed. Neurotransmitters that trigger central sensitization include excitatory amino acids and peptides. Evidence for this is that co-activation of N-methyl-D-aspartate and NK1 receptors can produce long-lasting increases in the responses of STT cells, and antagonists of these receptors prevent central sensitization. Responses to excitatory amino acids increase and those to inhibitory amino acids decrease during central sensitization, presumably accounting for the changed excitability of STT cells. We believe these changes result from the activation of signal transduction pathways, including the protein kinase C, NO/protein kinase G and protein kinase A cascades. Recent evidence shows that calcium/calmodulin dependent kinase II (CaMKII) is also upregulated early in the process of central sensitization and that several types of ionotropic glutamate receptors become phosphorylated. It is proposed that the phosphorylation of neurotransmitter receptors leads to alterations in the sensitivity of these receptors and to central sensitization. Comparable events occur during LTP in brain structures.
Willis
William D
WD
Department of Anatomy and Neurosciences and Marine Biomedical Institute, University of Texas Medical Branch, 301 University Avenue, Galveston, TX 77555-1069, USA. wdwillis@utmb.edu
D000818:Animals; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000502:physiology; D006801:Humans; D006930:Hyperalgesia / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000502:physiology*; D009415:Nerve Net / Q000166:cytology / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000502:physiology; D010766:Phosphorylation; D017470:Receptors, Glutamate / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*; D013788:Thalamus / Q000166:cytology / Q000502:physiology*
D018846:Excitatory Amino Acids; D018377:Neurotransmitter Agents; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D002211:Capsaicin