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Pain Neuroanatomy
Sarah Ashley Low, MD; Colin J. McCarthy, MB, BCh, BAO, MRCSI, FFR (RCSI); Rafael Vazquez, MD
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KEY FACTS

  • Terminology

    • Background

      • Pain Circuitry

        TERMINOLOGY

        • Definitions

          • Pain: Unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage
          • Nociception: Physiological processes that result from painful stimuli
          • Central sensitization: Hypersensitized pain state that develops due to plastic changes within pain circuitry after exposure to intense &/or prolonged noxious stimulation
          • Allodynia: Nonpainful sensation is perceived as painful
          • Hyperalgesia: Abnormally increased sensitivity to painful sensation
          • Preemptive analgesia: Preprocedural delivery of analgesic agent in anticipation of pain related to tissue injury
          • Differential Block: Neural conduction blockade of specific types of afferent fibers, such as nociceptors, due to their physical properties, including diameter and degree of myelination

        Background

        • Pain and Its Circuitry

          • Primary Afferent Neuron Modalities and Properties

            • Peripheral Axons: 1st-Order Neuron

              • Spinal Cord: 2nd-Order Neuron

                • Cortical Processing: Context and State Dependence

                  • Brainstem: Gatekeeper of Pain

                    Selected References

                    1. Koch SC et al: Spinal circuits for touch, pain, and itch. Annu Rev Physiol. 80:189-217, 2018
                    2. François A et al: A brainstem-spinal cord inhibitory circuit for mechanical pain modulation by GABA and enkephalins. Neuron. 93(4):822-39.e6, 2017
                    3. Whalley K: Pain: A gatekeeper circuit. Nat Rev Neurosci. 18(4):195, 2017
                    4. Han S et al: Elucidating an affective pain circuit that creates a threat memory. Cell. 162(2):363-74, 2015
                    5. Miranda J et al: Effect of pain chronification and chronic pain on an endogenous pain modulation circuit in rats. Neuroscience. 286:37-44, 2015
                    6. Finan PH et al: The association of sleep and pain: an update and a path forward. J Pain. 14(12):1539-52, 2013
                    7. Purves D: Neuroscience. Sunderland, Mass: Sinauer Associates, 2012
                    8. Hall J et al: Guyton and Hall Textbook of Medical Physiology. 12th ed. Philadelphia, Pa: Saunders/Elsevier. 563-4, 2011
                    9. Ong AD et al: Psychological resilience predicts decreases in pain catastrophizing through positive emotions. Psychol Aging. 25(3):516-23, 2010
                    10. Loyd DR et al: The role of the periaqueductal gray in the modulation of pain in males and females: are the anatomy and physiology really that different? Neural Plast. 2009:462879, 2009
                    11. Fields H: State-dependent opioid control of pain. Nat Rev Neurosci. 5(7):565-75, 2004
                    12. Skljarevski V et al: The nociceptive flexion reflex in humans -- review article. Pain. 96(1-2):3-8, 2002
                    13. Jaffe RA et al: Differential nerve block. Direct measurements on individual myelinated and unmyelinated dorsal root axons. Anesthesiology. 84(6):1455-64, 1996
                    14. Fink BR: Mechanisms of differential axial blockade in epidural and subarachnoid anesthesia. Anesthesiology. 70(5):851-8, 1989
                    15. Fields HL: Neurophysiology of pain and pain modulation. Am J Med. 77(3A):2-8, 1984
                    16. Pain terms: a list with definitions and notes on usage. Recommended by the IASP Subcommittee on Taxonomy. Pain. 6(3):249, 1979
                    17. Melzack R et al: Pain mechanisms: a new theory. Science. 150(3699):971-9, 1965
                    18. Sherrington C: The Integrative Action of the Nervous System. Oxford: Oxford University Press, 1906
                    Related Anatomy
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                    References
                    Tables

                    Tables

                    KEY FACTS

                    • Terminology

                      • Background

                        • Pain Circuitry

                          TERMINOLOGY

                          • Definitions

                            • Pain: Unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage
                            • Nociception: Physiological processes that result from painful stimuli
                            • Central sensitization: Hypersensitized pain state that develops due to plastic changes within pain circuitry after exposure to intense &/or prolonged noxious stimulation
                            • Allodynia: Nonpainful sensation is perceived as painful
                            • Hyperalgesia: Abnormally increased sensitivity to painful sensation
                            • Preemptive analgesia: Preprocedural delivery of analgesic agent in anticipation of pain related to tissue injury
                            • Differential Block: Neural conduction blockade of specific types of afferent fibers, such as nociceptors, due to their physical properties, including diameter and degree of myelination

                          Background

                          • Pain and Its Circuitry

                            • Primary Afferent Neuron Modalities and Properties

                              • Peripheral Axons: 1st-Order Neuron

                                • Spinal Cord: 2nd-Order Neuron

                                  • Cortical Processing: Context and State Dependence

                                    • Brainstem: Gatekeeper of Pain

                                      Selected References

                                      1. Koch SC et al: Spinal circuits for touch, pain, and itch. Annu Rev Physiol. 80:189-217, 2018
                                      2. François A et al: A brainstem-spinal cord inhibitory circuit for mechanical pain modulation by GABA and enkephalins. Neuron. 93(4):822-39.e6, 2017
                                      3. Whalley K: Pain: A gatekeeper circuit. Nat Rev Neurosci. 18(4):195, 2017
                                      4. Han S et al: Elucidating an affective pain circuit that creates a threat memory. Cell. 162(2):363-74, 2015
                                      5. Miranda J et al: Effect of pain chronification and chronic pain on an endogenous pain modulation circuit in rats. Neuroscience. 286:37-44, 2015
                                      6. Finan PH et al: The association of sleep and pain: an update and a path forward. J Pain. 14(12):1539-52, 2013
                                      7. Purves D: Neuroscience. Sunderland, Mass: Sinauer Associates, 2012
                                      8. Hall J et al: Guyton and Hall Textbook of Medical Physiology. 12th ed. Philadelphia, Pa: Saunders/Elsevier. 563-4, 2011
                                      9. Ong AD et al: Psychological resilience predicts decreases in pain catastrophizing through positive emotions. Psychol Aging. 25(3):516-23, 2010
                                      10. Loyd DR et al: The role of the periaqueductal gray in the modulation of pain in males and females: are the anatomy and physiology really that different? Neural Plast. 2009:462879, 2009
                                      11. Fields H: State-dependent opioid control of pain. Nat Rev Neurosci. 5(7):565-75, 2004
                                      12. Skljarevski V et al: The nociceptive flexion reflex in humans -- review article. Pain. 96(1-2):3-8, 2002
                                      13. Jaffe RA et al: Differential nerve block. Direct measurements on individual myelinated and unmyelinated dorsal root axons. Anesthesiology. 84(6):1455-64, 1996
                                      14. Fink BR: Mechanisms of differential axial blockade in epidural and subarachnoid anesthesia. Anesthesiology. 70(5):851-8, 1989
                                      15. Fields HL: Neurophysiology of pain and pain modulation. Am J Med. 77(3A):2-8, 1984
                                      16. Pain terms: a list with definitions and notes on usage. Recommended by the IASP Subcommittee on Taxonomy. Pain. 6(3):249, 1979
                                      17. Melzack R et al: Pain mechanisms: a new theory. Science. 150(3699):971-9, 1965
                                      18. Sherrington C: The Integrative Action of the Nervous System. Oxford: Oxford University Press, 1906