3_ PHYSIOLOGY OF PAIN; HUMAN PHYSIOLOGY .pptx

An overview of pain receptors, pathways and responses.

1. PAIN

2. What is pain? IASP: Unpleasant sensory and emotional experience attributed to potential or actual tissue injury Most ailments cause pain Pain is a protective mechanism Diagnosis depends to a great extent on a clinician’s knowledge of different qualities of pain

3. OBJECTIVES Know peripheral nerve fibers and receptor types that mediate nociception Differentiate fast and slow pain Explain hyperalgesia and allodynia Explain referred pain Know the pathway of pain transmission Explain the pain suppression system(modulation)

4. Nociceptors Non-adapting or adapt very little Free nerve endings: Mechanical nociceptors Thermal nociceptors Chemical sensitive nociceptors Polymodal nociceptors

5. Nociceptors Impulses from nociceptors transmitted via two fiber types Adelta fibers; thin myelinated – fast pain Unmyelinated C fibers – slow pain

6. Mechanical nociceptors Respond to strong pressure e.g from a sharp object

7. Thermal nociceptors Activated by skin temperatures above 45 or severe cold below 0

8. Chemical sensitive nociceptors Respond to various agents like: Bradykinin* (most painful) Histamine Hydrogen ions Potassium**( inc ’ intensity) serotonin Environmental irritants Proteolytic enzymes*( serine in pancreatitis) Substance P &prostaglandins inc ’ sensitivity to nerve endings but do not directly stimulate them.

9. Polymodal nociceptors Respond to combinations of noxious mechanical, thermal or chemical stimuli (MTC)

10. Intensity of pain Correlates with the rate of tissue damage rather than the total damage that has already occurred

11. Types of pain and their qualities Fast pain vs Slow pain Acute pain vs Chronic pain

12. Fast pain Sharp/Pricking pain Felt after 0.1 sec of stimulus application Assoc with mechanical and thermal stimuli

13. Slow pain Burning, aching, throbbing, nauseous pain (BANT) Assoc with all forms of stimuli Felt about 1 sec of stimulus application Usually assoc with tissue damage Causes prolonged unbearable suffering

14. Pain pathways Pain from the body – via spinal cord Pain from face via trigeminal (V) that enters the pons, descend to the medulla, where they cross over and ascend to the thalamus The ascending pathway sends branches not only to thalamus and the cerebral cortex but also to the limbic system (emotions) and hypothalamus (autonomic reaction) The result is that pain may be accompanied by emotional distress and autonomic reactions such as nausea, vomiting or sweating

15. Pain transmission pathways Two pathways corresponding to the two types of pain Fast pain pathway Slow pain pathway

16. Pain transmission pathways

17. http://webanatomy.net/anatomy/spinothalamic.jpg

18. Pain transmission pathways

19. Pain transmission pathways Fast Pain Slow Pain Dorsal root Laminae 1 Laminae 2/3 then to 5 Neurotransmitter at dorsal root Glutamate (instant but transient action) Mainly substance P (slowly released) Pathway Anterolateral spinothalmic ; Neospinothalamic Anterolateral spinothalamic ; Paleospinothalamic (spinalreticulothalamic) Localization Easy to localize Poorly localized because of the multisynaptic , diffuse connectivity Projections Thalamus and to cortex mostly but also to reticular areas Projections to reticular areas of midbrain – mediates arousal – unable sleep if pain severe

20. Which of the following is TRUE of nociceptors? Are rapidly adapting Include polymodal nociceptors Include Myelinated nerve endings Are usually in close association with type A-alpha nerve fibers Thermal nociceptors are low threshold compared to warmth and cold thermoceptors

21. Hyperalgesia Exaggerated response to noxious stimulus Substance P and prostaglandin E2 increase sensitivity to nociceptive stimuli Primary hyperalgesia – hypersensitivity of pain receptors themselves ( eg sunburned skin with locally released inflammatory factors) Secondary – by facilitation of sensory transmission ; lesions in the spinal cord or thalamus

22. Hyperalgesia

23. Allodynia Sensation of pain in response to an innocuous stimulus Attributable to increased sensitivity to pain

24. Visceral sensory pain pathways Collected by interoceptors within the closed ventral body cavities The interoceptors include nociceptors , thermoreceptors , tactile receptors, baroreceptors and chemoreceptors The axons of the 1 st order neuron usually travel with the autonomic motor fibers innervating the same visceral structures 2 nd order neurons within the spinal cord use the spinothalamic pathway and arrive to the medulla oblongata Cranial nerves V, VII, IX and X carry visceral sensory information also to the medulla

25. VISCERAL PAIN Poorly localized, unpleasant, associated with autonomic symptoms Usually radiates or is referred Mediated via nociceptors ; few and sparse in viscera Afferent fibers reach CNS via SNS and PNS nerves (cranial and spinal)

26. REFERRED PAIN Noxious stimulus in a visceral organ producing pain that is felt in a distant somatic structure Attributable to development from same embryonic segment or dermatome (the dermatomal rule) Convergence-projection theory ; convergence of somatic and visceral pain fibers on the same second order neuron

27. Referred pain Model : Organ receptors and cutaneous receptors converge on common spinal interneurons Purves Box 10B

28. Analgesia system Degree of reaction to pain is variable; partly due to an intrinsic pain control system Levels Brain and Spinal cord (descending opiate system) Gate control Theory - Local tactile sensory signals (large A-beta fibers)

29. The Descending Brain opiate system

30. Periaqueductal Gray (PAG): The PAG, located in the midbrain, serves as a central hub for descending pain modulation. It receives input from various brain regions involved in pain perception and stress responses and sends inhibitory signals to the spinal cord to modulate pain transmission. Rostral Ventromedial Medulla (RVM): The RVM, located in the brainstem, receives input from the PAG and other brain regions involved in pain processing. It contains both facilitatory and inhibitory neurons that project to the spinal cord and modulate the activity of pain-signaling neurons. Endogenous Opioid Peptides: The DBOS relies on the release of endogenous opioid peptides, including beta-endorphins, enkephalins, and dynorphins, which bind to opioid receptors located on neurons in the PAG, RVM, and spinal cord. Activation of these receptors inhibits the release of pain neurotransmitters, such as substance P and glutamate, leading to a reduction in pain perception. Descending Pathways: The DBOS utilizes descending pathways from the PAG and RVM to modulate pain transmission at the spinal cord level. These pathways can either inhibit or facilitate the activity of pain-signaling neurons in the dorsal horn of the spinal cord, depending on the context and intensity of the pain stimulus.

31. The Gate-Control Theory of Pain Figure 10-12a Pain can be suppressed in the dorsal horn level. Normally, tonically active inhibitory interneuron inhibit ascending pathways for pain

32. The Gate Control Theory of Pain Modulation Figure 10-12b Fibers from nociceptors synapse on the inhibition interneuron When activated, the fibers send message to block the interneurons and pain travels to the brain

33. The Gate Control Theory of Pain Modulation Figure 10-12c In the gate control theory of pain modulation fibers carrying sensory information about mechanical stimuli help block pain transmission Those fibers synapse on the interneuron and increase its inhibitory activity If both pain stimulus and nonpainful stimulus arrive at the same time, there will be partial inhibition of pain The sensation of pain will be perceived by the brain as lower Explains why rubbing a bumped elbow lessens the pain feeling

34. Pain in clinical setting Diagnosis – duration, location, character, radiation, relieving and aggravating factors Treatment: Antiinflammatory drugs Opiods

35. Free nerve endings contain receptors that encode which of the following sensations? Fine touch Muscle length Temperature Pressure Vibration

36. A patient with a c-fiber neuropathy will have impaired: A. Fast pain sensation B. Slow pain sensation C. Two point discrimination D. Patella tendon/knee jerk reflex red/rouge yellow/ jaune orange green/ vert

37. Medial dorsal Ventral medial post. Summary of ascending pain projections

38. Pain Channelopathies For reference