BMS150_PAT2-09p1_Pain_Win2023 (1).pdf

Pathophysiology of Pain BMS 150 Week 9 References Principles of Neural Science (Eric Kandel) Chapter 20 Principles of Neurology (Adams and Victor) Chapter 7 Neuroscience Online https://nba.uth.tmc.edu/neuroscience/m/s2/chapter06. html Pain - Introduc...

Pathophysiology of Pain BMS 150 Week 9 References Principles of Neural Science (Eric Kandel) Chapter 20 Principles of Neurology (Adams and Victor) Chapter 7 Neuroscience Online https://nba.uth.tmc.edu/neuroscience/m/s2/chapter06. html Pain - Introduction Definition: unpleasant sensation and emotional experience associated with actual or potential tissue damage, or described in terms of such damage ▪ The emotional aspect of pain makes it unique – no other sensation has the same ability to impact mood and quality of life Pain perception is very subjective ▪ People can suffer serious injuries during battle or athletic events and feel very little pain (until the event is over or danger has lessened) ▪ People can have little to no evidence of tissue damage but still report experiencing significant amounts of pain Types of Pain and Abnormal Sensation Term Definition Dysesthesia Any abnormal sensation described by a patient as unpleasant Paresthesia A sensation that is typically described as “pins-and-needles” or “prickling”, but is not notably unpleasant Analgesia Reduction or loss of pain perception Anaesthesia Reduced perception of all touch & pain sensation Hypoalgesia Decreased sensation and raised threshold to painful stimuli Hyperalgesia Exaggerated pain response from a normally painful stimulus Allodynia Abnormal perception of pain from a normally non-painful mechanical or thermal stimulus Hyperesthesia Exaggerated perception of a touch stimulus Causalgia Burning pain in the distribution of a peripheral nerve Pain is puzzling The neuroanatomical “localization” of pain is difficult to fully define ▪ Lesions of the thalamus, cortex, and other “higher” locations of the spinothalamic tract often cannot completely eliminate pain Only multiple lesions of the spinal cord seem to be capable of completely removing painful sensations in a particular area of the body ▪ One cannot elicit pain by stimulating the cortex directly – other areas need to be stimulated (i.e. thalamus, hypothalamus) for pain to be perceived Pain does not exhibit adaptation, unlike almost all other perceptions (touch, taste, smell) The central nervous system regulates perception and transmission of pain from lower levels, using multiple different molecules and pathways Pain transmission can actually cause inflammation in peripheral tissues Physiology of nociception Nociceptors are widely distributed through multiple depths in the skin ▪ “Dermal pain” tends to be described as sharp or burning Nociceptors are also widely distributed through many visceral organs ▪ Skeletal/cardiac muscle – dull, pressure-like pain ▪ Joints (synovium) and bones (periosteum) – many different characteristics (sharp, dull, aching) ▪ Blood vessels – usually dull ▪ Nerve roots and meninges ▪ Hollow viscera – often dull, cramping but can be sharp ▪ Mesothelial linings (peritoneum, pleura, pericardium) – often sharp ▪ Many organs can cause a dull pain due to stretching of the capsule Physiology of nociception Types of nociceptors: Thermal nociceptors – activated by temperatures > 45 C or less than 5 C Mechanical nociceptors – activated by intense pressure applied to a structure (i.e. skin) Polymodal nociceptors – activated by high intensity mechanical, chemical, or thermal stimuli Silent nociceptors – receptors that are widely distributed through viscera (but can also be found in the skin) that do not normally transmit pain information ▪ Only “awakened” in a setting of continuous damage or inflammation Physiology of nociception All nociceptors appear to be very simple neurons under the microscope – two major types: C fibres – unmyelinated axons with cell body in the dorsal root ganglia ▪ Conduction velocity: 0.5 – 2 m/sec ▪ Responsible for conducting slow pain and thermoception (temperature) ▪ Often dull, poorly-localized pain (large receptive fields) ▪ C-fibres also carry itching sensations Physiology of nociception All nociceptors appear to be very simple neurons under the microscope – two major types: A-delta fibres – myelinated axons with cell body in the dorsal root ganglia ▪ Conduction velocity: 12 – 30 m/sec ▪ Responsible for conducting sharp, “pricking” pain as well as some thermoception (temperature) ▪ Usually well-localized (smaller receptive fields) What can nociceptors detect? Very wide range of ion channels expressed in the free nerve endings, which allows them to detect a wide range of stimuli that can be associated with damage to tissue The transient-receptor potential receptors (TRP) are capable of recognizing a wide range of tissue insults: ▪ Cold and heat ▪ Low pH and free radicals ▪ Capsaicin ASIC receptors are receptors that can detect low pH (typical of ischemia or tissue damage) What can nociceptors detect? Nociceptors also express receptors for molecules that are released during inflammatory processes ▪ Prostaglandins – most are G-protein-coupled receptors that block potassium channels (leading to depolarization) ▪ Bradykinin – activated by pro-inflammatory, pro- coagulant processes protein that circulates in the bloodstream (kininogen) is activated to form bradykinin in situations involving tissue damage ▪ Histamine ▪ Substance P – released from a wide range of tissues ▪ Serotonin, acetylcholine, ATP What can nociceptors detect? Activation of some receptors in found in nociceptive neurons can increase the activation of other receptors ▪ Example – bradykinin can increase the activation of TRP receptors Bradykinin sensitizes the TRP receptor, making it more likely to open Neuroanatomical Pain Pathways Spinothalamic tract is the major nociceptive sensory pathway peripheral afferent pain fibers of both A-δ and C types have their cell bodies in the dorsal root ganglia ▪ central extensions of these nerve cells project, via the dorsal root, to the dorsal horn of the spinal cord ▪ Within the spinal cord, many of the thinnest fibers (C fibers) form a discrete bundle, the tract of Lissauer Peripheral afferent fibres usually terminate within the same segment as their spinal nerve ▪ Some extend rostrally a segment or two ▪ FYI – synapse in a wide range of dorsal horn lamina I, II, V, VII ,VIII Neuroanatomical Pain Pathways Spinothalamic tract – basic review Spinothalamic Tract – additional details Ascending pain pathways – additional details The fibres of the spinothalamic tract usually cross over (2nd order neurons) two or three levels superior to where the 1st-order neurons enter the spinal cord ▪ The fibres of 1st order neurons tend to ascend in a small fibre bundle (the tract of Lissauer) before crossing over and synapsing Another tract – the paleospinothalamic pathway – travels a somewhat different route ▪ Fibres ascend in the cord more medially ▪ Project through the medulla and synapse within a different set of thalamic nuclei (the intralaminar nuclei) ▪ Also synapse in a wide variety of other brainstem areas: Midbrain reticular formation, peri-aqueductal gray matter, hypothalamus May be responsible for much of the emotional distress and mood impacts of pain Ascending pain pathways – additional details Visceral pain sensation likely ascends along the anterior spinothalamic tract, and better-localized skin-associated pain sensation likely ascends via the lateral spinothalamic tract  The concept of fast pain and slow pain Fast pain – well- localized, sharp pain carried by A-delta fibres Slow pain – poorer- localized, duller ▪ Carried by C- fibres ▪ Tends to last longer