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Neurochemistry of Pain Sensation References: - Essentials of Pain Medicine (Benzon) - Principles of neural science (Kandel) - Textbook of Medical Physiology (Guyton) By: Dr H. Najafi, Associate Professor, medical physiology.

pain Types of pain The sequence of events by which a stimulus is perceived - Transduction - Transmission - Modulation - Perception

Pain receptors and their stimulation by inflammatory soup

Neurochemistry of somatosensory processing at peripheral sensory nerve endings CGRP NO: released by damaged afferents, further sensitize nearby neurons, augmenting pain and inflammation. Peripheral anti- hyperalgesic mechanisms Capsaicin

Peripheral Second Messenger Pathways

Cyclic adenosine monophosphate (cAMP) second messenger (G s )

The cell membrane phospholipid second messenger system (Gq)

Physiologic classification of nerve fibers

Dual pathway for transmission of pain (Neospinothalamic) (paleospinothalamic) Anterior commissure

Transmission of the pain into the brain stem, thalamus and cerebral cortex -Reticular areas -Ventrobasal complex -Posterior nuclear groups of the thalamus 1- Reticular nuclei 2- The tectal area 3-The periaqueductal gray region - Intralaminar and ventrolateral nuclei of the thalamus Capability of pain signal to arouse nervous excitability

Neurochemistry of somatosensory processing in the spinal dorsal horn

Neurochemistry of pain transmission in spinal cord Excitatory Neurotransmitters: - Glutamate and aspartate - ATP - Substance P and neurokinin A - CGRP - CCK

Inhibitory Neurotransmitters - Glycine and GABA - Norepinephrine (Alpha-2 Clonidine) - Serotonin - Adenosine - Acetylcholine - Somatostatin, the enkephalins, and possibly dynorphin

Descending pathway for modulation of nociception at the supraspinal level

Supraspinal modulation of nociception Pain matrix (anterior cingulate cortex, amygdala, and prefrontal cortex) Periaquaductal gray (PAG) Rostral ventromedial medulla (RVM): On cells and Off cells Dorsal root ganglion +-+-

Analgesia system of the brain and spinal cord

Inhibition of pain transmission by tactile sensory signals

The localized modulation of pain can be explained by the gate control hypothesis

Nonadapting nature of pain receptors (Hyperalgesia)

Hyperalgesia Peripheral (primary) (Histamine, Bradykinin, PG. E2, Sbs. P) Central (secondary)

Peripheral hyperalgesia

Central hyperalgesia

Referred pain

Causes of True Visceral Pain Ischemia Chemical Stimuli Spasm of a Hollow Viscus Overdistention of a Hollow Viscus

Mechanism of referred pain

Visceral and parietal transmission of pain from the appendix

Surface area of referred pain from different visceral organs

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