Pain, Somatosensation, PDF

Pain http://criticalscience.com/chronic-pain-psychosocial-  Objectives Define the anatomy of the ascending vertical tracts involved in transmitting pain (location in spinal cord, and entire neural axis) – Spinothalamic – Spinomesencephalic – Spinore...

Pain http://criticalscience.com/chronic-pain-psychosocial-  Objectives Define the anatomy of the ascending vertical tracts involved in transmitting pain (location in spinal cord, and entire neural axis) – Spinothalamic – Spinomesencephalic – Spinoreticular – Spinolimbic For each ascending pathway listed above: – State the modality subserved by the pathway and function of the pathway, – Identify the receptor responding to that modality in the periphery, – State the location of cell bodies and all relevant synapses (1, 2, and 3) in the ascending pathways of the somatosensory system, – Identify the cortical areas receiving the input; Discuss the clinical significance of the organization of the system;  Other Notes Pain is complex Pain is not equal to nociception The ascending pathways that generate awareness of pain include a complex network of structures Plasticity in the pain system can cause clinical complexity and intractable pain.  “An unpleasant sensory and emotional experience associated with actual or potential or no tissue damage “ Essential to survival! A warning signal for the organism to identify and avoid a potentially harmful situation. Multiple factors influence and regulate the perception of pain. http://www.medscape.org/ Pain can affect emotional, autonomic, and viewarticle/446350_3 social function Nociception: activation of specialized receptors by tissue damage.  Nociceptors Free nerve endings Non-myelinated Non adapting Specialized High threshold Adequate stimulus: – Mechanical: high threshold for pressure – Thermal (heat, cold), threshold temp. causes tissue damage – Chemical agents: Bradykinin, serotonin, histamine, K+, acids, Ach, proteolytic enzymes, etc. Sensitization: repeated stimulation decreases threshold Nociceptors Pain receptors  2 kinds of afferent fibers Fast Pain: Sharp, pricking, acute, fast pain - A (delta) fibers (fast, 6-30m/sec) - High spatial resolution well localized - Underlies flexion withdrawal - Reaches the cortex (awareness) - Also called spinothalamic pain Slow Pain: Burning, aching, dull, slow pain - C fibers (slow, 0.5-2m/sec) - Low resolution---> often only to gross body part - Large psychological and emotional component  René Descartes (1596–1650) was a creative mathematician, an important scientific thinker, and an original metaphysician In 1644, René Descartes theorized that pain was a disturbance that passed along nerve fibers until the disturbance reached the brain His theory transformed the perception of pain from a spiritual, mystical experience to a physical, mechanical sensation.  Pain Pathways* Transmit Nociception Temperature Non-discriminative (crude) touch Spinothalamic Tract (Fast Pain) 3-neuron pathway Conscious (reaches cortex) Indirect Pathways (Slow Pain) Spinomesencephalic Spinoreticular Spinolimbic * There is no one ‘pain’ pathway  Fast Pain: Spinothalamic Tract 1 Brings info into spinal cord 3 (primarily Aδ fibers) 2 Crosses the midline and projects to 3 thalamus 1 Projects to the cortex 2  Spinothalamic Tract Order 1 Neuron st Free nerve endings are the primary peripheral receptors for nociceptive stimuli Cell bodies of the peripheral afferent axon are located in the dorsal root ganglion The axon of the 1st order neuron enters the spinal cord through the dorsal root entry zone (largely in rexed lamina I and II ) Upon entry, the neurons form the dorsolateral tract of lissauer  Spinothalamic Tract Order 1 Neuron st Anterior Commissure Transmitted by (primarily Aδ fibers) - High threshold, fast conducting axons. Upon entry into the cord, either synapse and cross over, or ascend/descend a few segments, and then synapse and cross over Spinothalamic Tract Order 1st Neuron Upon entering the cord, the axons may bifurcate into short ascending and descending branches; they then synapse with 2nd order neurons in the dorsal horn. These collaterals play an important role in intersegmental reflexes. Spinothalamic Tract Order 2 Neuron nd May synapse at same level as the 1st neuron entered the cord, or a few segments above/below The decussating fibers travel through the anterior commissure to reach the contralateral side of the spinal cord. Here, they ascend as spinothalamic tracts Very (somatotropically) organized !  Spinothalamic Tract Order 2 Neuron nd Sends projections primarily to the VPL (ventral posterior lateral) nucleus of thalamus; also to other 2 thalamic nuclei (ventral posterior inferior, intralaminar nuclei) Comprises the lateral spinothalamic (large) and anterior spinothalamic (smaller) tracts - considered together as the anterolateral system Spinothalamic Tract  Spinothalamic Tract Order 3 Neuron rd 3 The VPL nucleus of the thalamus gives rise to fibers that course upward in the posterior limb of the internal capsule Terminate in the postcentral gyrus (Primary Somatosensory Cortex or S-I). Some fibers also terminate in the secondary somatosensory (SS) cortex or S-II  3 Trigeminal Lemniscus 1 1st order neurons from the face travel through the trigeminal nerve; transmit fast pain, temperature, and crude touch These fibers enter the Pons, then 1 2 descend to the medulla and upper cervical cord before synapsing in the spinal nucleus of trigeminal nerve 2 2nd order neurons cross midline and ascend in the trigeminal lemniscus to the VPM nucleus of thalamus. 3 3rd order neurons project to the Somatosensory cortex Summary - Fast Pain: Spinothalamic Tract After a fracture, rapid onset of sharp, localized pain. Perception of location and intensity of tissue damage (real or potential) As inflammation proceeds (chemical soup is formed), increased sensitivity of areas surrounding painful site Slow Pain: Indirect Pathways Elicit motivation, withdrawal, arousal, autonomic responses to pain. Also called the Medial System because most axons synapse in the CNS close to the midline Comprised of 3 pathways: – Spinoreticular – Spinomesencephalic – Spinolimbic Indirect Pathways: Receptors Nociceptors respond to noxious heat, chemical or mechanical stimuli (Polymodal) Afferent information carried by C fibers (small diameter, unmyelinated) High threshold Become sensitized with repeated stimulation. i.e. after injury, can be activated with less stimulation. Tissue damage releases a chemical soup (histamine, prostaglandins, etc) that can sensitize nociceptors Indirect Pathways: Central Component 1st order afferent enters spinal cord via dorsal root (cell body in DRG); synapses with interneurons in lamina I, II, and or V or dorsal horn Neurotransmitter = substance P Interneurons send axons to synapse with ascending projection fibers 2nd order neuron fibers ascend to Midbrain = Spinomesencephalic Reticular formation =Spinoreticular Limbic system 2 =Spinolimbic 1  Spinomesencephalic Tract Carries nociceptive info to 2 parts of the midbrain (mesencephalon) 1. The periaqueductral gray matter and midbrain raphe nuclei, both of which give rise to fibers that modulate nociception, and are part of the descending pain inhibition system Some fibers also terminate in the parabrachial nucleus, which sends fibers to the amygdala, an important structure for processing emotions within the limbic system. These fibers mediate the emotional components of pain 2 2. The superior Colliculus in the midbrain tectum. Role in turning the upper body, head, 1 and eyes in the direction of painful stimulus http://www.sciencedirect.com/science/article/pii/S0006899304001052  Spinoreticular Tract Some axons ascend ipsilaterally, some decussate (i.e. bilateral projections). These tracts form multiple synaptic connections in the reticular formation on the way to the intralaminar thalamic nucleus. The reticular activating system is involved in arousal, attention, and sleep/wake cycles. Thus activation of this pathway is 1 involved in the process that commands 2 attention to pain & interferes with sleep Intalaminar thalamic nuclei project to the striatum (caudate nucleus and putamen  Spinolimbic Tract Transmit nociception to the intralaminar thalamic nuclei. 2 Intalaminar thalamic nuclei project to the striatum (caudate nucleus and putamen of BG), S-I, S-II, cingulate gyrus, insula, amygdala, and prefrontal cortex. Provide the affective, emotional dimension to pain e.g. if the anterior cingulate gyrus is removed, pain intensity is unchanged but pain interferes less with behavior/ social activities 1 Eventually projects to diverse areas of cerebral cortex involved  Summary: Indirect Pathways After a fracture, associated with automatically directing eye/head toward painful stimulus, moving away from harmful stimulus, becoming pale, faint, nauseous, emotionally distressed. Not well localized, entire hand appears to hurt! Summary: Sites of Synapses &Termination of Pain Stimuli Fast Pain Slow Pain  Comparison of direct and indirect pathways for pain transmission Direct (fast) Indirect (slow) Tract Lateral-STT Spinolimbic, Spinomesencephalic Spinoreticular tract (SRT) Origin Lamina I & IV, V Lamina I, IV,V, (and VII, VIII) Somatotopic Yes No organisation Body representation Contralateral Bilateral Synapse in reticular No Yes formation Sub-cortical targets None Hypothalamus Limbic system Autonomic centres Thalamic nucleus Ventral posterolateral Intra-laminar nuclei (VPL) Other midline nuclei Cortical location Parietal lobe (SI Cingulate gyrus, Insula cortex) Role Discriminative pain (quality intensity, Affective-arousal location) components of pain Other functions Temperature http://www.frca.co.uk/article.aspx?articleid=100118  Summary: Fast versus Slow Pain Immediate and Can follow sharp pain, sharp pain dull ache, diffuse Reaches conscious May not reach awareness conscious awareness Good localization of Poor localization of site of pain site of pain Aδ fibers C fibers Fast conducting Slower conducting (reaches the cord in (reaches the cord in ~0.03 second) ~0.5 second) ‘The (Complete) Pain Experience’  structures that process and regulate pain The (Pain) Matrix can create pain in the absence of nociceptive input! http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1571498/ TEDxAdelaide - Lorimer Moseley Why Things Hurt http://tedxtalks.ted.com/video/TEDx-Adela ide-Lorimer-Moseley-W  Pain Modulation The CNS can suppress the incoming nociceptive stimuli at different levels in the transmission pathway Peripheral Pain Control: 1) The Gate Control Theory Peripheral activation of inhibitory interneurons in spinal cord Central Pain Control 2) Descending or Central biasing Inhibition of Lamina I, II, V neurons from midbrain-medulla Descending Opiate-induced analgesia Release of endogenous opiates in spinal cord  Neurotransmitters and Pain Excitatory: Glutamate, substance P, neurokinin A and B, etc. Inhibitory: Gamma amino butyric acid (GABA) Descending pain regulation: Norepinephrine, serotonin, opiates The Pain Gate Melzack & Wall (1965) proposed the 1st scientific explanation of how pressure and touch stimuli inhibit pain. Hypothesis: Info from 1st order nociceptive neurons and 1st order low-threshold mechanoceptor neurons converges on the same 2nd order neuron. Transmission of pain can be blocked at the substantia gelatinosa (SG) of the spinal cord through a “pain gate” The Pain Gate 1 C and Aδ fibers bring nociceptive signals to SG from peripheral receptor 2 3 They inhibit SG inhibitory neuron and activate the 2nd order 1 4 spinothalamic tract 3 neuron (gate is open) 2 Touch fibers (Aß) activate the SG inhibitory neuron and this inhibits the 2nd 4 order inhibitory Example: neuron (gate closed) Rubbing a painful area reduces pain sensations. Inhibitory Pain is processed right at its entry into the CNS – in theneuron dorsal horn. prevents nociceptive At the dorsal horn, nociceptive stimulus processing could be normal, suppressed (e.g. TENS), sensitized, or impulses from reaching reorganized. The Pain Gate How does this relate to the mechanism of action of - TENS? - Massage? Transcutaneous Electrical Nerve Stimulation Descending Analgesia Opiates (e.g. morphine) produce powerful pain relief Opiates bind to opiate receptors in the CNS They are anti-nociceptive! The CNS synthesizes endogenous opiates to modulate nociception –Enkephalins (‘in the head’) –Beta-endorphins (‘morphine within’) –Dynorphins (‘dynamo+morphine’) Stress-induced anti-nociception: - During accidents, athletic contests, etc. - Release of endorphins from pituitary gland and adrenal medulla!  Descending Analgesia: Opioidergic The Periaqueductal gray matter (PAG) is the origin of the most prominent opioidergic pain control (descending) pathway. The PAG excites neurons in several brainstem nuclei including, the serotonergic nucleus raphe magnus (NRM) and the noradrenergic locus ceruleus (LC) Transmitter release in spinal cord depresses ascending pain information  Descending Analgesia: Opioidergic 1 The axolemma of the central terminals of the 1st order neurons contain opioid receptors. 2 2 The serotonin-releasing neurons from higher centers like raphe nucleus descend to terminate in the 3 3 spinal cord SG Here they form excitatory 4 synapses with an 4 inhibitory interneuron 1 The inhibitory interneurons release opioids (enkephalins or  Descending Analgesia: Norepinephric Dorsolateral pontine reticular formation is the site of origin of norepinephrine (adrenergic, non-opioid) analgesic pathway that descends to synapse with the SG in the spinal cord Terminate in inhibitory interneurons within the SG, which in turn inhibits the 2nd order nociceptive neuron ‘Natural’ Analgesia: Sites of Anti-nociception ‘Artificial’ Analgesia: Sites of Anti-nociception Clinical: Effects of Lesions in the Pain Pathways  Syringomyelia A cyst (called syrinx) forms within the spinal cord; the cyst expands and elongates over time, destroying a portion of the spinal cord from its center and expanding outward. As the syrinx widens it compresses and injures nerve fibers in its proximity The syrinx interrupts the decussating spinothalamic fibers that mediate pain and temperature sensibility, resulting in loss of these http://www.ninds.nih.gov/disorders/syringomyelia/  Phantom Pain Pain from a body part that is no longer there How mobile phones are turning into phantom limbs http://blogs.telegraph.co.uk/technology/adrianhon/ 100006561/how-mobile-phones-are-turning-into- phantom-limbs/ Scientific American, October, 2013 Posted on Blackboard under “Resources from the Web”  Nociception = Pain? Aδ Fibers + C Fibers = Pain?? IF this was true … We should see no change in pain without a change in nociception. Very Cold (-20°C) Stimulus And we should see no Associated With A Red Or A Blue Light. change in nociception without a change in pain. is a change in pain without a change in nociception. Coiurtesy Eric Oetter; McMahon et al 201 Nociception versus Pain Moseley 2013  Pain Sensitization Tissue injury with inflammation produces spontaneous pain and hyper- responsiveness to stimuli and to movement (hyperalgesia). Such sensitization includes PNS and CNS components termed peripheral sensitization and central sensitization respectively. Sensitization clearly evolved to minimize use of injured and fragile tissue. e.g. Tissue inflammation increases the sensitivity of nociceptive endings in peripheral tissues by means of a complex chemical soup of mediator molecules (histamine, serotonin, prostaglandins, cytokines). Nociceptors become prone to activation by weak Pain is an output related to perceived threat of body tissue. And understanding this helps. Moseley 2013  Pain, Physical Therapy, and You! Pain is in the Brain The importance of talking to your patient The importance of understanding pain biology The importance of explaining pain biology to your patient http:// The importance of healthsciencetechnology.wikispaces.com/ Physical+Therapy keeping up with pain research The Bane of Pain is Plainly in the Brain by Allan Busbaum, PhD Was this known to that student of pain The Marquis de Sade was his name. Now pain is an intricate potion His charisma it gripped you as he of sensations cognitions emotions smilingly whipped you Acute pain may be terrible And the pain could just drive you insane. and when chronic unbearable Not something that you treat The good news is there are myriad ways with mere lotions. to control pain Which is perhaps why cutting the cord is But although pain may not be easy to bear on the wane. there’s a reason for pain being there. Find out what the morphine dose is, It’s critical to know even consider hypnosis. lest the cancer unbeknownst grow Pain signals are needed for repair. Remember pain is a complex product of the brain. You learned of children with congenital In this regard find a pregnant woman and insensitivity to pain. ask her They are unaware if they have fractures or Is Lamaze merely a ploy to distract her? sprains. Or when labor pain is not perceived by These children are rare but they need the brain constant care, Are endorphins a relevant factor? Or their injuries cannot be contained. Now of course of endorphins there are The small fibres you learned are essential numerous classes. To establish a painful potential. Some, reportedly, are as potent as But shake your hand or vibrate and you may grasses. https://www.somasimple.com/forums/showthread.php?t=61  Summary: Why do we feel pain? Because … Serotonin Histamine Immune response Tissue damage Hyperalgesia Axon reflex, allodynia Peptides (Substance P, opioids) Prostaglandins (& other metabolites) Edema Nitric oxide Sympathetic NS contribution  TEDxAdelaide - Lorimer Moseley Why Things Hurt http://tedxtalks.ted.com/video/TEDx-Adelaide-Lorimer-M oseley-W her books by Dr Lorimer Moseley Explain Pain Painful Yarns