Role of neurotransmitters in sensitization of pain responses.
Injection of capsaicin into the skin results in pain, primary heat and mechanical hyperalgesia, and secondary mechanical allodynia and hyperalgesia. Sensory receptors in the area of secondary mechanical allodynia and hyperalgesia are unaffected, and so the sensory changes must be due to central actions of the initial intense nociceptive discharge that follows the capsaicin injection. Central sensitization of the responses of spinothalamic tract neurons lasts several hours, but can be prevented by spinal cord administration of non-NMDA and NMDA glutamate receptor antagonists or NK1 substance P receptor antagonists. The long-lasting increase in excitability of spinothalamic tract cells depends on the activation of several second messenger cascades (PKC, PKA, and NO/PKG signal transduction pathways). The excitability change also depends on activation of calcium/calmodulin-dependent kinase II, which is consistent with the proposal that this central sensitization response is a form of long-term potentiation.
Willis
W D
WD
Department of Anatomy and Neurosciences, University of Texas Medical Branch, Galveston 77555-1069, USA. wdwillis@utmb.edu
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002211:Capsaicin / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology / Q000633:toxicity; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D000882:Haplorhini; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D007271:Injections, Intradermal; D017774:Long-Term Potentiation; D008465:Mechanoreceptors / Q000502:physiology; D017551:Microdialysis; D023421:Models, Animal; D008959:Models, Neurological; D009475:Neurons, Afferent / Q000502:physiology; D018377:Neurotransmitter Agents / Q000494:pharmacology / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000139:chemically induced / Q000503:physiopathology*; D010766:Phosphorylation; D020671:Posterior Horn Cells / Q000502:physiology; D011499:Protein Processing, Post-Translational; D051381:Rats; D011955:Receptors, Drug / Q000187:drug effects* / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000502:physiology; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013133:Spinothalamic Tracts / Q000473:pathology / Q000503:physiopathology*; D013373:Substance P / Q000037:antagonists & inhibitors / Q000502:physiology
D001713:Biphenyl Compounds; D018690:Excitatory Amino Acid Agonists; D018377:Neurotransmitter Agents; D011955:Receptors, Drug; D016194:Receptors, N-Methyl-D-Aspartate; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D013373:Substance P; D002211:Capsaicin; C066892:CP 96345