Lecture Slides: Neurophysiology and Classification of Pain PDF

The neurophysiology and classification of pain Dr Brooke Coombes [email protected] Ouch – right? Ouch – right? Pain can be experienced without tissue damage. Extensive tissue damage may not be painful. All pain is real Learning outcomes • Describe the processes involved in pain per...

The neurophysiology and classification of pain Dr Brooke Coombes [email protected] Ouch – right? Ouch – right? Pain can be experienced without tissue damage. Extensive tissue damage may not be painful. All pain is real Learning outcomes • Describe the processes involved in pain perception & pain modulation • Describe peripheral and central sensitization • Define nociceptive, neuropathic and nociplastic pain mechanisms • Discuss how psychosocial factors influence pain Prevalence of pain Economic burden of pain Pain management by physiotherapists • Pain reduction is a primary goal of physiotherapy for patients who present with acute or persistent pain • Physiotherapists must have an understanding of the processes involved in pain perception, the main categories of pain and how to evaluate signs and symptoms • The evidence for pain mechanisms will continue to evolve • We do not know how all treatments produce their effects The building blocks of pain Understanding pathophysiology (3rd Ed, Chap 7) Davidson’s 23rd Ed Building blocks of pain Receptors • Are present in peripheral tissues • Receptors respond to a specific stimuli • Mechanoreceptors respond to stimuli such as touch, pressure or vibration • Thermoreceptors respond to thermal (heat or cold) stimuli • Ion channels allow ions to pass though and produces electrical impulse • Mechanoreceptors and thermoreceptors have a low threshold for stimulus Building blocks of pain Nociceptors • Nociceptors are really just receptors that respond to strong stimuli that are harmful or potentially harmful to tissues • Are present in tissues that produce pain • Nociceptors respond to several stimuli (e.g. heat, cold, mechanical or chemical) i.e. they are polymodal • Nociceptors require a high threshold for stimulus ie a strong stimulus Building blocks of pain 1st order neurons • First-order neurons (sensory afferent neurons) carry information from the periphery to the spinal cord, where they synapse with second-order neurons • Different sensory neurons display different properties à responsible for different sensations Building blocks of pain 1st order neurons • Types: • Aβ fibres carry non-painful information from mechanoreceptors and thermoreceptors • Large and myelinated à fast conduction • Are responsible for touch, pressure, vibration, proprioception, heat and cold sensations Building blocks of pain 1st order neurons • Types: • Aδ (delta) & C fibres carry information from nociceptors • Aδ fibres– small, myelinated à fast conduction • Are responsible for sharp + localized pain • C fibres – small, unmyelinated à slow conduction • Are responsible for dull + diffuse pain The building blocks of pain • 2nd order neurons • Signals from nociceptors cross over to the contralateral side of the spinal cord and relay information to the thalamus via the spinothalamic tract • Signals from mechanoreceptors follow the same general pathway but cross at the level of the medullar rather than the spinal cord and are grouped in different tracts Davidson’s 23rd Ed The building blocks of pain • 3rd order neurons • Relay information from thalamus to cerebral cortex • It is here that a person becomes aware of pain. Davidson’s 23rd Ed Building blocks of pain Brain • There is no single brain area responsible for pain • Multiple structures are responsible for perception, localization, emotional and attentional aspects of pain and memory formation Davidson’s 23rd Ed Building blocks of pain Brain • There is no single brain area responsible for pain • Multiple structures are responsible for perception, localization, emotional and attentional aspects of pain and memory formation Davidson’s 23rd Ed Building blocks of pain Descending pain pathways (red) • Neurons from various parts of the brain synapse in the brainstem and descend to the spinal cord • These descending pathways modulate pain by inhibiting or facilitating input arriving at the spinal cord • Under normal circumstances there is descending inhibition Davidson’s 23rd Ed Building blocks of pain Local inhibitory interneurons (light blue) • Aβ, Aδ and C fibres carry information from the periphery to 2nd order neurons AND inhibitory interneurons • Inhibitory interneurons can inhibit or stimulate transmission of nociceptive information at this spinal level • This is known as ‘spinal gate’ mechanism Projection neuron=2nd order neuron Davidson’s 23rd Ed Building blocks of pain Spinal gating • Non-noxious input (Aβ) can close the "gate" to noxious input (Aδ and C) by activating the inhibitory interneuron • Noxious input (Aδ and C) “opens” the gate, by inhibiting the inhibitory interneuron Building blocks of pain • Neurotransmitters / “neuromodulators” • Substances are released by neurons and transmit signals to other neurons that change the activities of these neurons • Excitatory (promote the action potential) eg. Prostaglandins, bradykinin, cytokines • Inhibitory (delay or stop the action potential) e.g GABA, serotonin, noradrenalin & endorphins There is no direct pathway involved in pain perception • Not all action potentials entering the spinal cord will reach the brain • Not every action potential that makes it to the brain, will result in experience of pain • The brain decides whether the signal should be interpreted as threatening (pain or no pain) • The brain decides what to make of it, how to feel about it, and what to do about it, if anything Davidson’s 23rd Ed Nociception and pain are different phenomena • Nociception is the process of sensory neurons detecting strong stimuli in the tissues • Pain is an aversive sensory and emotional experience typically caused by, or resembling that caused by, actual or potential tissue injury (IASP Taskforce 2019) Pain modulation Pain modulation • Our pain system has a tremendous capacity for modulation (change) • Occurs at multiple levels and by multiple events • Some events are short-lasting and reversible e.g. change in ion channels • This change is protective, because it helps healing by limiting use of an injured part until the injury is fully repaired • Other events cause more prolonged modifications e.g. transcriptiondependent processes • This would not be helpful, because pain outlasts the period of tissue healing (pain is overprotective) Pain modulation • Amplification of neural signaling can occur in the periphery and / or central nervous system • Peripheral sensitization • Central sensitization • Explains how pain can be triggered by innocuous (not harmful) stimuli and be maintained in absence of noxious stimulus Peripheral sensitisation • Sensitisation of nociceptive neurons in the periphery can enhance or prolong the pain experience • Often initiated by tissue damage or inflammation Peripheral sensitisation - Mechanisms • Inflammatory mediators released by damaged cells cause sensitisation of nociceptors • It lowers the threshold of nociceptors so that they respond to less stimulus “chemical soup” Basbaum 2009 Central sensitization (CS) • Sensitisation of neurons within the CNS (spinal cord, brainstem and cortex) Central sensitization (CS) • Represents a state in which pain can be triggered by less intense inputs and maintained by less intense inputs or by a different kind of input • While nociceptive input is required to trigger CS, it can be maintained in the absence of active peripheral tissue damage Davidson’s 23rd Ed Central sensitization - Mechanisms No single mechanism explains CS, may involve • Increased membrane excitability • Synaptic facilitation • Decreased activity of the inhibitory neurons (disinhibition) • Enlargement of receptive fields • Wide dynamic neurons become responsive to both non-noxious and noxious stimuli Davidson’s 23rd Ed How does sensitisation present clinically? • Patients with sensitization may display some or all the following: • Widespread hyperalgesia • Allodynia • Wind-up or temporal summation • Widespread pain • Spontaneous pain e.g. stabbing, electric shock sensations Wind-up or temporal summation • Is the consequence of cumulation or summation of action potentials Wind-up or temporal summation • Is the consequence of cumulation or summation of action potentials Hyperalgesia • Is where mildly noxious stimuli are perceived as painful Hyperalgesia • Is where mildly noxious stimuli are perceived as painful Allodynia • Is where pain due to a stimulus that does not normally provoke pain Allodynia • Is where pain due to a stimulus that does not normally provoke pain How can we measure these phenomenon? • Quantitative sensory tests can be used to examine responses to graded stimuli Peripheral vs Central sensitisation • Peripheral sensitisation contributes to a large proportion of pain from acute local injury • Central sensitisation contributes to a large proportion of pain in chronic widespread pain conditions e.g. fibromyalgia • Some conditions can have high levels of both e.g. non-specific back pain, rheumatoid arthritis, osteoarthritis, tendinopathy