The Neurobiology of Pain

1. The Neurobiology of Pain

2. What is Pain? • Pain is part of the body's defense system. • The reflex reaction to escape painful stimulus is meant to adjust behavior to avoid the harmful situation in the future.

3. Sensation & Perception of Pain • The sensation of pain consists of four distinct processes: • Transduction • Transmission • Interpretation • Modulation

4. Transduction • Nociceptors are stimulated in skin and muscle. • Noxious stimulus affects a periphery sensory nerve ending. • Neuron is depolarized. • Electrical impulse is generated

5. Transmission • Impulse is transmitted or carried throughout the nervous system. • Spinothalamic tract is the most important pathway for transmission. • We will come back to this

6. Interpretation • Subjective interpretation of pain. • How does it feel? • Sharp, Dull, Ache, Burn, etc. • Behavioral, psychological, and emotional factors involved.

7. Modulation • Modulation can either suppress or aggravate pain. • Neural response. • Peptides, amino acids, neurotransmitters and other mediators are released. • Chemical messages are released.

8. Transduction

9. Nociception • Sensory neurons, called nociceptors, are found in every part of the body that can sense pain. • Skin, muscle, joints, and the digestive tract. • When exposed to noxious stimuli, an action potential is generated and driven from the periphery toward the CNS • There are four main categories of nociceptors: Thermal, Chemical, Mechanical and Sleeping.

10. Types of Nociceptors • Thermal Nociceptors: • Detect hot or cold noxious stimuli. • Mechanical Nociceptors: • Detect noxious pressure or deformation, such an an incision. • Chemical Nociceptors: • Respond to many different types of chemicals, including capsaicin. • Sleeping / Silent Nociceptors: • Only respond to post-injury inflammation.

12. Types of Nociceptive Pain • Superficial Somatic pain is caused by injury to the skin or superficial tissues • produces a sharp, localized pain of short duration. • Deep Somatic pain originates from ligaments, tendons, bones, and muscles. • Produces a dull, aching, non-localized pain of longer duration. • Visceralpain originates from the body’s organs. • Produces more of an aching or cramping pain that is of a longer duration than somatic pain

13. Pain Pathway

15. Transmission • Activation nociceptors by noxious stimuli generates signals that travel to the dorsal horn of the spinal cord. • How?

16. Peripheral Nerves • Nerves can either be slow or fast. • The slower type neural fibers are deeper in the skin and transmit signals at a rate of 1-2 meters per second on un-myelinated C neurons. • The fast type pain sensors require an intense stimulus to activate and transfer signals that are perceived as acute sharp stinging pain at a rate of  5 to 30 meters per second along myelinated A Delta neurons 

17. The Spinal Cord • The signal reaches the Dorsal Horn of the spinal cord. • Action potentials induce neurotransmitter release. • Voltage gated sodium ion channels • Glutamate (fast) binds to ionotropic AMPA and NMDA receptors.

19. The Brain • From the dorsal horn, the signals are carried along the Spinothalamic Tract to the Thalamus, Cortex, PAG and other regions of the brain.

20. The Descending Pain Pathway • The descending pathway of the spinal processing of nociceptive input is relayed through the: • Periaqueductal gray • Frontal Cortex • Insula • Amygdala • Hypothalamus • Brainstem

22. Other Types of Pain • Inflammatory pain • This type of pain results from the cascade of biochemical events that are initiated with tissue damage. • Neuropathic pain • Pain generated independently by the nervous system resulting directly from action on nerves, such as severing. May also result from the culmination of physiological processes that are set in motion by persistent nociceptive or inflammatory processes.

23. Inflammatory / Neuropathic Pain

24. Treatment

25. NSAID’s • Non Steroid Anti Inflammatory Drugs • The most prominent members of this group of drugs are aspirin, ibuprofen, and naproxen. • They act as non-selective inhibitors of the enzyme cyclooxygenase. • Inhibition of COX-1 and COX-2 • Cyclooxygenase catalyzes the formation of prostaglandins. • Prostaglandins act as messenger molecules in the process of inflammation

26. Cox-2 Inhibitors • A form of NSAID that directly targets COX-2. • i.e., Celebrex and Vioxx • Similar in effectiveness to NSAID’s, but do not cause the gastrointestinal problems common to non-specific COX inhibitors. • May increase the risk for heart attack and stroke

27. Opioids • Opioids are commonly prescribed for moderate to severe pain. • Morphine, Vicodin, OxyContin, etc. • They work by blocking the transmission of pain signals to the brain. • Many side effects • Addiction, tolerance, risk for overdose, respiratory depression. • We will explore this class of drugs in depth next lecture.

28. Off – Label Perscriptions • Some medications typically prescribed for other non-pain conditions can be used for pain relief of certain conditions. • Axiolytics (Benzodiazepines) • Antidepressants (SSRI / Tricyclic) • Anticonvulsants • Muscle Relaxers

29. Nociceptor Peripheral Nerve Descending Pathway Ascending Pathway Interneuron Spinal Cord Sympathetic Efferent's

30. Antidepressants Anticonvulsants Anxiolytics Opioids Opioids NSAID’s Tricyclics Alpha-2 Agonists Alpha-1 Blockers NMDA Receptor Blockers Opioids