Pain physiology

anesthesia and pain physiology

1. PHYSIOLOGY PAIN MODERATOR-Dr. Atul Bansal Presenter : Dr. Richa Kumar

2. “Physical adjunct of an imperative protective reflex” -Sherrington Involves an immensely complex mechanism because when tissue is damaged  central nocicetive pathways are sensitized and reorganized which lead to persistent or chronic pain IASP defines it as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage” Nociception is defined as unconscious activity induced by a harmful stimulus applied to sense organs What is PAIN?

3. The experience of pain involves a series of complex neurophysiologic processes that reflect four distinct components— 1.Transduction 2. Transmission 3. Modulation 4. Perception NEUROBIOLOGY OF PAIN

4. 1.TRANSDUCTION Mechanical, thermal, or chemical energy is converted into an electrical action potential (transduction) capable of propagating (transmission) along the nerve fibre toward the spinal cord when the resting threshold of a nociceptor is exceeded

5. Inflammatory mediators ( bradykinin , prostaglandins, serotonin, histamine, cytokines) are released in response to tissue injury . Not constitutively stored and are synthesized de novo Bradykinin is viewed as the first mediator to cause activation of second messengers, resulting in increased sodium ion channel conductance and sensitization . Prostaglandins enhance the activity of bradykinin and contribute to inflammatory responses A-δ Fibers and C Fibers Exposure to inflammatory mediators causes A-δ fibers and C fibers to undergo peripheral sensitization so that their stimulus thresholds are decreased and their firing and intensity is increased and prolonged

6. Free nerve endings receptors present in skin, muscles, joints, viscera, and vasculature. MECHANICAL: strong pressure, sharp objects THERMAL: burning heat (>45 degrees C, noxious cold) CHEMICAL:pH extremes, environmental irritants,endogenous neuroactive substances POLYMODAL: sensations mediated by A δ and C fibres NOCICEPTORS

7. Nociceptors provide information to CNS regarding the location and intensity of noxious stimuli They are inactive until they are stimulated by sufficient energy to reach threshold stimulus Thus prevent random signal propagation to the CNS for interpretation of pain

8. SENSITIZATION OF NOCICEPTORS : refers to increased responsiveness of peripheral neurons responsible for pain transmission to heat ,cold, mechanical or chemical stimuli Attributable to inflammatory mediators In acute inflammation usually resolves and nociceptors reach normal resting threshold Chronic pain occurs if inflammation condition doesn’t resolve leading to sensatization of peripheral and central pain signalling pathway and increased pain sensations to normal painful stimuli ( HYPERALGESIA ) OR Perception of pain sensations in response to normally nonpainful stimuli ( ALLODYNIA ) Type I & II hyperalgesia

9. 2.TRANSMISSION Pain signals are transmitted from nociceptors along myelinated A-δ fibers (rapid conduction for early response) and unmyelinated C fibers (slow conduction for more delayed response). These afferent fibres enter the spinal cord through the dorsal nerve roots and terminate on cells in the dorsal horn of the spinal cord and thalamus with projections to the cingulate, insular, and somatosensory cortexes .

10. FAST PAIN SLOW PAIN Sharp pain Dull,throbbing,nauseous Pricking aching stabbing burning “ good pain ” “acute pain” “ bad pain ” Responsible for flexor withdrawl syndrome Associated with autonomic stimulation (nausea, vomiting) 2-5 mcm diameter 0.4-1.2 mcm 12-30 m/s conduction rate 0.5-2 m/s A δ ( myelinated ) (type III) C fibres ( unmyelinated ) Stimulus: mechanical/thermal Chemical ( bradykinin ) NT: glutamate Substance P CLASSIFICATION OF PAIN TRANSMISSION

11. Primary nociceptive transmission in the spinal cord  Glutaminergic (N-methyl-D- asparate ; NMDA) synapses do not participate significantly in primary nociceptive transmission,  crucial role in spinal sensitization.  even after complete NMDA blockade in the spinal cord,  primary afferent nociceptive information is transmitted to the thalamus. NMDA antagonists thus have an antihyperalgesic rather than an analgesic effect in the spinal cord

12. Relay centre Perception & discrimination of peripheral painful stimuli Perception of motivational-affective components of pain amygdala , hippocampus, thalamus, hypothalamus , basal ganglia, and cingulate gyrus . The amygdala is emotion centre of the brain hippocampus  formation of new memories about past experiences Periaqueductal gray-RVM=may depress or facilitate integration of painful information involved with  emotion formation and processing, learning, and memory.

13. DORSAL HORN: RELAY CENTRE FOR NOCICEPTION: The dorsal horn consists of 6 laminae (total 10) Laminae I and II  superficial dorsal horn C fibres synapse Laminae V  WDR and nociceptive specific (NS) neurons Myelinated fibres from muscles & viscera  I,IV , VII Non- myelinated from these organs I, II, V, X Interneurons are important for integration and modulation of incoming nociceptive information

14. Spinal dorsal horn functions as a relay centre for nociception and other sensory activity C- fibres synapse in lamina II k/a SUBSTANTIA GELATINOSA OF ROLANDO

15. ORGANIZATION OF DORSAL HORN SYSTEMS THAT CONTRIBUTE TO THE PROCESSING OF NOCICEPTIVE INFORMATION

16. ASCENDING PATHWAYFOR PAIN TRANSMISSION: These are important for perception & integration of nociceptive information Major ascending pathways are: 1. spinothalamic tract (STT)  direct projection to thalamus 2. spinomedullary projections 3.Spinobulbar projections 4. spinohypothalamic tract Indirect projections- dorsal column, spinocervicothalamic pathway pathway from medulla trigeminal sensory nuclei which process nociceptive information from facial structures. Homeostatic contro l

17. SCAN

18. Fibres travelling in STT originate from: Spinal dorsal neurons in lamina I (A δ & C) Laminae IV &V (A β ) Laminae VII & VIII (convergent inputs from skin & muscle, joint inputs) Lateral STT originates from laminae I cells Posterior STT originates from deeper laminae V & VII

19. Scan spinal cord

20. Spinobulbar projections originate from similar neurons as those in STT ( laminae I, V, VII) Spinohypothalamic projections originate B/L from laminae I ,V, VII & X

21. 3.MODULATION T he process of altering pain transmission . Both inhibitory and excitatory mechanisms modulate pain (nociceptive) impulse transmission in the PNS and CNS .

22. PERIPHERAL MODULATION : either through the liberation or elimination of chemicals in the vicinity of the nociceptor Tissue injury  substance P and glutamate directly stimulate nociceptors Other mediators ( bradykinin , histamine, prostaglandins, serotonin, potassium and hydrogen ions, and lactic acid) further sensitize and excite nociceptors and act as mediators of inflammation MODULATION OF NOCICEPTION

23. SPINAL MODULATION : Nociceptive Afferent Signals The excitatory amino acid transmitters glutamate and aspartate and several neuropeptides (vasoactive intestinal peptide, calcitonin, neuropeptide Y) modulate transmission of nociceptive afferent signals in the spinal cord . Substance P is also an important neuromodulator that can enhance or aggravate pain . Inhibitory Substances involved in the regulation of afferent impulses in the dorsal horn include γ- aminobutyric acid (GABA), glycine, enkephalins , endorphins, norepinephrine, dopamine, and adenosine.

24. SUPRASPINAL MODULATION : 1.Descending Inhibitory Tracts at the brain stem level originate from cell bodies located in the region of the periaqueductal gray matter. 2.Nerve Fibers identified as participants in inhibitory modulation include the opioid system and associated neurotransmitters (endorphins, enkephalins , other neuropeptides). 3.A-δ and C Fibers Neurotransmitters released from these projections hyperpolarize A-delta and C fibers . 4.Monoamine Pathway In addition to opioid descending inhibitory pathways, a monoamine pathway originates from locations in the periaqueductal gray matter

25. PAG-RVM CONNECTION IS CRITICAL FOR PAIN MODULATION

26. COGNITIVE MODULATION patient's ability to relate a painful experience to another event Another area of perception is attention (RAS), which presumes that only a fixed number of afferent impulses can reach cortical centers biofeedback or hypnosis

27. Repetitive discharge of primary afferent nociceptors Temporal summation of post synaptic A.P. NMDA receptor activation Pain increases with each successive stimulus (wind up) even though stimulus intensity is same After peripheral nerve injury light touch can produce pain( allodynia ) Repeated light touch can produce progressive increasing pain (summation) CENTRAL SENSITIZATION OF DORSAL NEURONS

28. Primary hyperalgesia results from tissue release of toxic substances. These toxic substances spread to adjacent tissues, prolonging the hyperalgesic state ( secondary hyperalgesia ). MECHANISM: Repetitive C- fiber stimulation( increase in frequency of release of neurotransmitters at intervals of 0.5 to 1.0 Hz )  summated  prolonged depolarizations of second-order neurons (“wind-up ”) & central sensatization This leads to secondary hyperalgesia , which by definition , is an increased pain response evoked by stimuli outside the area of injury. NEUROPLASTICITY

29. Schematic representation of peripheral and spinal mechanism involved in neuroplasticity NEUROPLASTICITY describes the dynamic modulation of neural impulses

30. GATE THEORY A β are faster than A δ /C)

31. Pain perception is thought to occur at the thalamus, with the cortex being important for discrimination of specific sensory experiences 4.PERCEPTION

32. DRUGS ACTING IN PAIN PATHWAY

33. The goal is to prevent NMDA receptor activation in the dorsal horn, which causes wind-up, facilitation, central sensitization expansion of receptive fields, and long-term potentiation, all of which can lead to a chronic pain In order for pre-emptive analgesia to be successful, three critical principles: ( 1) the depth of analgesia must be adequate enough to block all nociceptive input during surgery, ( 2) the analgesic technique must be extensive enough to include the entire surgical field, and ( 3) the duration of analgesia must include both the surgical and postsurgical periods. Patients with pre-existing chronic pain tend to respond poorly to pre-emptive techniques because of pre-existing sensitization of the nervous system PREEMPTIVE ANALGESIA

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