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Pathophysiology of Pain Treatment of Acute Postoperative Pain. Dr Sajith Damodaran. University College of Medical Sciences & GTB Hospital, Delhi. Objectives: . Definition of Pain Anatomy and Physiology of pain perception Adverse effects of untreated postoperative pain
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Pathophysiology of PainTreatment of Acute Postoperative Pain Dr SajithDamodaran University College of Medical Sciences & GTB Hospital, Delhi
Objectives: • Definition of Pain • Anatomy and Physiology of pain perception • Adverse effects of untreated postoperative pain • Modalities of treating postoperative pain • Special patient populations
Pain: Definition An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage. [IASP] • Subjective • Sensation and emotion • Unpleasant • Psychological, in absence of any stimulus or pathophysiological cause
Pain: Definition • Pain is what the patient says hurts [John Bonica] • Affected by the mental and emotional state, preconditioning, past experiences and memories. • Always subjective. Varies from person to person • Pain is the Fifth vital sign [JCAHCO]
Acute Pain • Normal predicted physiological response to an adverse chemical, thermal or mechanical stimulus. • Generally lasts less than one month • Poorly managed pain leads to chronicity • Pathophysiological changes in both PNS & CNS
Anatomy and Physiology of Pain Nociceptive Receptors: • Naked Nerve Endings • In all tissues • Specific for pain • Stimulus not specific • Pain is not produced by overstimulation of other receptors
Anatomy and Physiology of Pain Nociceptive Pathways: • Afferent • Three neuron • First order neurons in Dorsal Root Ganglia • Second order neurons in Dorsal horn • Third order neurons in Thalamic nuclei • Second order neurons include nociceptive specific and WDR • Dual ascending system • Lateral corticospinal • Dorsal column medial leminiscal • Descending modulation by cortex thalamus and brain stem
Anatomy and Physiology of Pain Fast Pain or First Pain: • Sharp or stinging • well localised • By stimulation of thermo-mechanical nociceptors • Carried by A delta fibres • Transmitted by the Lateral spinothalamic tract • Monosynaptic pathway • Usually disappears when stimulus ends
Anatomy and Physiology of Pain Slow Pain or Second Pain • Delayed, Diffuse • Stimulation of polymodalnociceptors • Carried by C fibres • Transmitted by the dorsalcolumn medial leminiscal tract • Polysynaptic pathway. Collaterals to midbrain, pontine and medullary RF, PAG, Hypothalamus • Engage Descending modulatory system • Involved in the reflex response to pain and emotional and motivational aspect
Anatomy and Physiology of Pain • Small Myelinated AδFibres • Carry Fast pain • 2-5 μm diameter • 12-30 m/s • End mainly in lamina I, II & V of dorsal horn • Small unmyelinated C Fibres • Carry slow pain • 0.4-1.2 μm diameter • 0.5-2 m/s • End in Lamina I & II of dorsal horn
Anatomy and Physiology of Pain Efferent modulation of pain: • Descending inhibition • Cortex, thalamus, brain stem PAG, nucleus raphemagnus, locus ceruleus • Descend in dorsal column to dorsal horn
Anatomy and Physiology of Pain Gate Control Theory: • Explains the highly variable and non linear relationship between pain and injury • Pain is ‘gated’ at the Dorsal Horn • Involves WDR neuron • Excited by nociceptors and also Aβfibres • Inhibitory interneurons, excited by Aβfibres, inhibited by Aδ and C fibres • MOA of TENS, Rubifascients and counterirritants
1.The projection neuron (P) carries both nociceptive stimulation from small fibers (S) and non-nociceptive simulation from large fibers (L) on the way to the brain. 2.With no stimulation, the inhibitory neuron (I) keeps the gate "closed," and there is no painful sensation. 3.With painful stimulation, the small fiber (S) blocks the inhibitory neuron (I), "opening" the gate for the projection neuron (P) to send on the painful stimulus. 4.With the addition of non-painful stimulation, the large fiber (L) activates the inhibitory neuron (I), partially or completely closing the gate depending on the strength of the stimulation, and competes with the painful stimulation for access to the projection neuron (P).
Anatomy and Physiology of Pain Other Types of Pain: • Deep Pain • Poorly localised, nauseating eg: periosteal pain, pain from ligaments • Muscle Pain • Due to ischemia • P factor. ? Potassium • Relieved by restoration of blood supply
Anatomy and Physiology of Pain • Visceral Pain • Poorly localised and dull – sparse receptor concentration • Usually felt in midline • Associated with nausea and autonomic disturbances • Afferents carried by ANS • Spinal pathways are same as for somatic pain • Referred to other areas
Anatomy and Physiology of Pain • Referred Pain • Dermatomal Rule • Pain from visceral sites referred to the somatic structure that developed from the same embryonic segment of dermatome • Role of experience: • Pain from abdominal structures may be referred to site of previous surgery • Role of convergence • Visceral and somatic sensory input converge on Dorsal Horn. • More fibres in the peripheral nerve than the STT
Anatomy and Physiology of Pain Neuropathic Pain: • Direct nerve damage like entrapment, cutting, traction, compression etc. • Presents with burning, tingling and other unpleasant sensations in addition to pain • Common surgical procedures • Limb amputations • Breast surgery • Gall bladder surgery • Thoracic surgery • Inguinal hernia repair • Responds poorly to typical analgesics
Anatomy and Physiology of Pain Pain Processing - 4 Elements • Transduction • Noxious mechanical, chemical and thermal stimuli are converted to action potential • Transmission • AP conducted through nervous system • Modulation • Alteration of neural transmission along the pain pathway, principally at dorsal horn • Perception • Final common pathway. Integration of painful input into somatosensory and limbic cortex. Usual analgesic approaches target only perception
Anatomy and Physiology of Pain Modulation: • Augmentation: • Sensitisation due to neuronal plasticity (acute pain induced changes in the CNS) • Inhibition: • GABA, Glycine by intrinsic neurons • NA, serotonin, Endorphins by descending efferent cortical and subcortical input
Anatomy and Physiology of Pain Chemical Mediators of Pain Processing: • Tissue damage and inflammation activate nociceptors • Release of numerous algogenic substances from the activated macrophages, mast cells, platelets and lymphocytes • Direct pain transduction and facilitation of transduction by increasing the excitability of nociceptors
Neurochemistry of impulse processing at peripheral nerve ending
Anatomy and Physiology of Pain Neurotransmitters in Spinal Cord: • Excitatory Amino Acids • Aspartate & Glutamate • Excitatory Neuropeptides • Substance P, Neurokinin A • Inhibitory Amino Acids • GABA, Glycine
Anatomy and Physiology of Pain Pain Receptors in Spinal Cord: • NMDA (N-methyly-D-Aspartae): Ca++ channel dependent • AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionicacid): Na+ channel dependent • Kainate: Na+ channel dependent • Metabotropic • Opioid Receptors: Inhibitory • Alpha2 Adrenergic Receptors: Inhibitory
Postoperative Pain Management: Why manage postoperative pain? • Humanitarian consideration • Improved quality of care • Better patient satisfaction • Lesser morbidity • ? Economic benefits due to enhanced patient well being and early rehabilitation
Assessment of pain Background Pain Pain that is persistant May vary over time Breakthrough Pain Pain that escalates above a persistant Background pain Transitory and Intermittant Pain that is episodic in the absence of background pain
Assessment of pain Simple Pain Scales: Useful for evaluation of acute pain • Visual Analouge Scale • Validated for research • Simple to use • Sensitive to small changes • Not useful in visually impaired, cognitively impaired and small children • Numerical Rating Scale • Less sensitive • Requires patient to be able • to translate pain severity to • number. • Not useful in visually impaired • cognitively impaired and children • Verbal Rating Scale • Easy to Use • Useful in mildly cognitively • impaired • Insensitive to small changes • in pain intensity
Assessment of pain • Useful in children <7 • Useful in non-verbal
Assessment of pain Useful for evaluating chronic pain Include pain intensity as well as mood, behaviour, thoughts and belifes, physiological effects and their interaction with each other • McGill Pain Questionnaire • Breif Pain Inventory • The Memorial Pain Assessment Card • Neuropathic Pain Scale • The Leeds Assessment of Neurpathic Symptoms and Signs (LANSS)
Assessment of pain • Best assessment: Ask & Listen • Features asked for during assessment: • Onset • Temporal Pattern • Site and Radiation • Characeter and Intensity • Exacerbating and Relieving factors • Associated symptoms • Response to analgesics, and other interventions • Interference with activities of daily living • Psychological effects
Strategies of Acute Pain Management • Proactiveness • Assess, treat, reassess • Have predefined pain treatment plan in place • Plan should be flexible to include breakthrough pain • Multimodal Approach • Treat all the possible steps in pain processing • Benefits: Synergism, lower side effects, flexibillity • Escalating Approach • Patient control • Patient controlled analgesia
Strategies of Acute Pain Management • Systemic Medications • Opioids • NSAIDs • NMDA Receptor Antagonists • Alpha-2 adrenergic agonists • Calcium Channel Ligands • Other Adjuncts: Lidocaine, Corticosteroids • Neuraxial Techniques • Epidural Analgesia • Intrathecal Analgesia • Peripheral Nerve/Plexus Blocks • Patient Controlled Analgesia • Non Pharmacological Methods
Strategies of Acute Pain Management: Pre-Emptive Analgesia • Prevention of Central Sensitisation and hyperexcitability induced amplification, at NMDA receptor. • Pre-requisites: • Adequate depth to block all nociceptive input during surgery • Extensive enough to cover the whole surgical field • Duration should include both surgical and post-surgical period • Theoretically can reduce acute postoperative pain/hyperalgesia and chronic pain after surgery • Definite evidence of clinical benefit lacking.
Systemic Medications: Opioids • Opioid Receptors: μ, κand δ receptors • Location of receptors: • Periphery following inflammation • Spinal cord dorsal horn • Supraspinally in the brainstem, thalamus and cortex • PAG, nucleus raphemagnus and RVM in descending pathway
Systemic Medications: Opioids Mechanism of Action: • Spinal • Inhibition of Ca++ influx presynaptically • Enhacing K+ efflux postsynaptically • Activation of descending inhibitory GABAergic circuit • Peripheral • Inhibition of release of proinflammatory and pronociceptive substances
Systemic Medications: Opioids Adverse Effects & Problems: • Respiratory Depression • Nausea and Vomiting • Sedation • Urinary Retention • Euphoria/Dysphoria • Constipation • Tolerance • Dependence and Addiction
Systemic Medications: Opioids Morphine: Most commonly used opioid for postoperative analgesia
Systemic Medications: Opioids TransdermalFentanyl Delivery System (Ionsys) • Needle free, patient activated system for in-hospital use • Iontophoresis • Low intensity electrical field used to transport fentanyl across skin into circulation • Each double click delivers 40mcg over 10 min • For us in adults > 18 years • Used for 24 hours or 80 doses
Systemic Medications: Opioids Oral TransmucosalFentanyl (ACTIQ): • To treat breakthrough cancer pain in opioid tolerant patients • To be sucked by placing in between cheek and lower gums • Each unit to be consumed in 15 minutes • Supplied in strengths of 200, 400, 600, 800,1200 & 1600mcg
Systemic Medications: Opioids Pethidine: Phenylpiperidine derivative μ and κ receptor agonist. Also has Na+ channel blocking and Atopinergic action
Systemic Medications: Opioids Tramadol: • Moderate affinity μreceptor agonist. • Acts on spinal modulating pathways • Inhibition of neuronal NA and Serotonin uptake • Stimulation of presynaptic serotonin release • Adverse Effects: • Nausea & Vomiting • Ondansetron interferes with analgesic effect • Non addictive, less sedation • Dose: 3 mg/kg IM/IV/PO for moderate to severe pain
Systemic Medications: Opioids Pentazocin: • Agonist-Weak antagonist • Dose 10-30 mg IV/ 50 mg PO for relief of moderate pain • Side Effects: • Dysphoria • Sedation • Tachycardia, Hypertension (catecholamine release)
Systemic Medications: Opioids Butorphanol: • Agonist-Antagonist • Dose: 2-3 mg IM • Also available as intranasal spray • Side Effects: • Sedation • Nausea • Tachycardia, hypertension • Less dysphoria than other agonist antagonists • Antagonise other opioids if used together