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Transcript
Neuroanatomy: Pain and Temperature (Walker) CLASSIC PAIN AND TEMPERATURE PATHWAY (ANTEROLATERAL SYSTEM): ALS is a crossed spinal pathway that transmits pain, temperature, itch and slow brush (sensual) touch ALS also known as the lateral spinothalamic tract First Order Neuron: o Cell body: in sensory dorsal root ganglion o Synapse: in dorsal horn of the spinal cord Second Order Neuron: o Cell Body: in dorsal horn o Path of Axon: project across the midline in the anterior white commissure (crossed axons end up one spinal level above where they came in); ALS then ascends in the anterior part of the lateral funiciulus Communicates with the reticular formation along the way (important regulator of autonomic function with ties to emotional centers of the brain) o Synapse: ventral posterolateral (VPL) thalamus (diencephalon) Third Order Neuron: o Cell Body: VPL of thalamus o Synapse: ipsilateral somatosensory cortex (areas 3,1,2) and the insular cortex FIRST ORDER NEURON: DORSAL ROOT GANGLION Function: o DRG neurons for ALS detect and transmit sensory information from skin and organs except brain tissue o Act as a sensor of organ homeostasis (informs the spinal cord of the physiological state of tissues); ALS is the primary alert system for tissue damage Example: detects damaging mechanical stress (mechanoreceptors) and temperatures (thermoreceptors) Transmittal Systems for Detecting Tissue Damage (2): o Aδ Fibers: myelinated for fast sharp pain (short duration) o C Fibers: unmyelinated for slow burning pain (long duration) Detecting Pain and Temperature: o DRG neurons use free nerve endings in the periphery to detect pain and temperature Thermoreceptors: detect temperature (sensitive to small changes) o Warm Receptors: 30-45°C (>45°C activates thermal nocireceptors) o Cold Receptors: 10-35°C (<10°C turns off these receptors; feel numb) Note: some cold receptors fire at temperatures >45°C; this provides the paradoxical feeling of cold if hot probe is place on a small skin region innervated by a cold receptor Nocireceptors: detect pain (activated by stimuli that may cause tissue damage) o Polymodal: non-selective for mechanical, thermal, and chemical stimuli (ie. cannot tell the difference between the 3); most nocireceptors are of this type o Unimodal: Mechanical: selective response to strong pressure Thermal: selective response to burning heat or extreme cold Chemical: selective response to histamine or other chemicals Path of DRG Axons: o Enter the spinal cord via the lateral division of the dorsal root o Once in the spinal cord, the fibers ascend and descend (one level up or down) in the posterolateral fasciculus (Zone of Lissauer); this allows for integration of sensory information at several spinal cord levels DRG Axon Synapses: o Synapse in the superficial and deep laminas of the dorsal horn at each respective spinal level Superficial (Laminas I-II): Contain modality specific neurons that respond to specific types of nociceptive or thermal stimuli Contain mechanical slow brush (sensual touch) neurons Both fast and slow pain impulses are mediated here Deep (Lamina III-V): Contain neurons that are NOT modality-specific; instead receive convergent input from multiple nociceptive and thermoceptive fibers Also receive mechanoreceptor input carrying proprioceptive information and descending supraspinal motor information Neurotransmitters Released by DRG Axons in the Dorsal Horn: o Glutamate: quick acting, excitatory; likely involved in fast sharp pain o Substance P: excitatory peptide transmitter; likely involved in slow burning pain Clinical Correlations: o Burning sensation when cold hands placed in warm water: polymodal nocireceptors that produce a burning feeling are normally suppressed by thermoreceptors active at ambient temperatures; when the temperature gets cold enough, these thermoreceptors are shut off and the nocireceptors can fire pain signals o Damaged tissue very sensitive to pain: tissue damage causes hyperalgesia (reduced pain threshold, increased paint intensity, or spontaneous pain); chemicals like prostaglandins that are released during damage also stimulate nocireceptors further o Referred Pain: there is a mixture of visceral and cutaneous nociceptive input onto neurons of the dorsal horn (creates “neural confusion”); results in nociceptive signals arising from viscera being perceived as pain from cutaneous regions o Rubbing helps reduce cutaneous pain: nociceptor activity in the dorsal horn is reduced by the simultaneous activity of low-threshold mechanoreceptors (Aβ receptors); mediated by inhibitory interneurons of the dorsal horn that suppress firing of the ALS secondary neuron (gate theory of pain) SECOND ORDER NEURON: SPINOTHALAMIC NEURON Cell Body: dorsal horn of the spinal cord Axons: project across midline through anterior white commissure to form the ALS (ends up one level above where it entered); ALS ascends in the anterior region of the lateral funiculus o Somatotopic Organization in the Spinal Cord: cervical, thoracic, lumbar, sacral (from medial to lateral) Position of ALS in the Brain Stem: o Medulla: ALS begins to be displaced dorsally and laterally by the inferior olivary nucleus o Pons: ALS lateral to the medial lemniscus o Midbrain: ALS shifted dorsolaterally with respect to the ML o Just Caudal to Diencephalon: ALS and ML fibers mix together as they penetrate the posterior thalamus ALS Synapse: o VPL Thalamus: receives somatotopically organized ALS information to provide conscious awareness of stimuli according to type and location, as well as signals regarding organ and tissue homeostasis o Reticular Formation: receives ALS (and other pain) information to arouse motor and emotional centers of the brain, as well as integrate information into autonomic nuclei including the hypothalamus Damage to ALS Pathway: o Damage in the lateral funiculus: contralateral loss of pain and temperature perception beginning 1 spinal level below the location of the lesion (and downward) o Damage to anterior white commissure (syringomyelia): cavitation of the spinal canal damages the anterior white commissure producing bilateral loss of pain and temperature perception beginning 1 spinal level below the cavitation (and downward) o Damage to ALS in the brainstem: loss of pain and temperature sensation of the contralateral body; some pain signals will rise to level of consciousness (reticular formation) but localization is lost Lesion of the dorsolateral medulla (Wallenberg Syndrome): damages the ALS and the spinal trigeminal system (mediates face pain); this causes a loss of pain and temperature in the contralateral body, as well as loss of pain and temperature sensation of the ipsilateral face Damage to VPL Thalamus: results in loss/impairment of all types of sensation on the contralateral side of the body (ML also terminates in the VPL thalamus); patients also experience spontaneous tearing pain (thalamic pain syndrome) which cannot be inhibited by routine pain-relievers or morphine (thought to be mediated by the reticular formation; does respond somewhat to anti-depressant medications) Surgical Approach to Reducing Chronic Pain: o Operation can be done to destroy the ALS within the spinal cord (cordotomy) o Performed several levels above the dermatomal level of agonizing pain and produces immediate contralateral analgesia o For many patients, pain returns after several months (because of pain fibers outside of the ALS that ascend to the brainstem; reticular formation) THIRD ORDER NEURON: THALAMOCORTICAL NEURON Cell Body: in the VPL thalamus Axon: project ALS information to o Somatosensory cortex (area 3,1,2): ipsilateral projection for conscious awareness; somatotopic organization discriminates type and location of the stimulus o Insular cortex: ipsilateral projection of tissue and organ homeostasis; sometimes called the interoceptive cortex Lesions of Somatosensory Cortex: o Lesions of postcentral gyrus disruopt fine discriminatory functions mediated by ML projections; however, pain and temperature sensations remain relatively intact THE EXPERIENCE OF PAIN AND TEMPERATURE- BEYOND THE ALS Experience of Pain: Pain can differ from individual to individual, as well as differ in the same individual at different times o Pain and temperature information is delivered to the reticular formation of the brainstem by way of ALS collaterals and spinoreticular axons ALS collaterals give off in the tegmentum of the medulla, pons and midbrain o Reticular formation relays pain and temperature signals to: Brainstem autonomic centers and hypothalamus (autonomic and endocrine integration) Anterior cingulate gyrus and limbic system (emotional integration) Intralaminar thalamus and basal ganglia (motor integration and arousal) o Therefore, it is hard to reduce pain by just treating the ALS Reticular Formation Nuclei Provide Feedback Directly to Dorsal Horn of Spinal Cord: Allows for regulation of primary DRG input from the periphery o Descending reticular fibers release serotonin (Raphe nuclei) and NE (Locus ceruleus) into the dorsal horn to excite enkephalin (opioid) inhibitory interneurons of the substantia gelatinosa (lamina II) o Part of the endogenous opioid (endorphin) system that naturally suppresses pain input from the periphery o Example: an athlete that gets injured during a game may not feel pain because of signals from the reticular fibers that modulate pain signals