Neuro 2 – Ascending Pathways PDF

NEURANAT 2 – Ascending pathways Revisions from Y1 General somatic: - Somatosensory pathways to consciousness o Medial division – DMCL 🡪 1° somatosensory cortex: proprioception (conscious muscle joint sense), vibration,...

NEURANAT 2 – Ascending pathways Revisions from Y1 General somatic: - Somatosensory pathways to consciousness o Medial division – DMCL 🡪 1° somatosensory cortex: proprioception (conscious muscle joint sense), vibration, position, discriminative touch. o Lateral division: ALS 🡪 1° somatosensory cortex: pain, thermal, light touvh and pressure - Unconscious somatosensory pathways o Lateral division: Anterolateral column – spinocerebellar tracts – cerebrellum Visceral tracts o Lateral division: anterolateral system – spinal lemniscus – primary somatosensory cortex: pain and stretch. The arrangement of grey and white matter is different at levels of the spinal cord. White matter consists mainly of axons and dendrites and is divided into ventral, lateral, and dorsal funiculi (L. funiculus), which are further divided into fasciculi. The cervical (C5 to T1) and lumbosacral (L1 to S2) enlargements are produced by expansions of the grey matter required to innervate the corresponding limbs at those levels. White matter most abundant in upper reaches of cord as it contains sensory & motor pathways for 4 limbs.  1. Types of neurons Interneurons are the smallest (5-20 microns). Their bodies contained within cord and send their axons into the white matter surrounding the grey matter and ascend or descend two or more segments, interconnecting different spinal cord segments. These latter processes are termed propriospinal fibres and form the fasciculi proprii. They participate in spinal reflexes and are intermediate cell stations between fibre tracts descending from brain & motor neurons projecting to cells of locomotion. Medium sized neurons (20-50 microns) are found in most of grey matter. Most are relay (projections) cells receiving inputs from dorsal root afferents & project their axons to brain. Projections are tracts, a functionally homogeneous group of fibres. α motor neurons 🡪 largest (50-100 microns). They are used for the supply of skeletal muscles. Scattered among them are γ motor neurons supplying muscle spindles. In medial part ventral horn lie Renshaw cells who perform a tonic inhibition upon alpha motor neurons 2. Sensations There are 2 kinds of sensations: - Conscious 🡪 perceived at cerebral cortex. They are either exteroceptive or proprioreceptive. o Exteroceptive sensations come from the external world. They impinge either on somatic receptors on the body surface or on telere- ceptors serving vision and hearing. Somatic receptors include touch, pressure, heat, cold & pain o Proprioceptive sensations arise within the body. The receptors concerned are those of the locomotor system (muscles, joints, bones) and of the vestibular labyrinth. The pathways to the cerebral cortex form the substrate for position sense when the body is stationary, and for kinaesthetic sense during movement. - Unconscious 🡪 not perceived but relayed to cerebellum. They are either proprioception or interoception. - Unconscious proprioception is the term used to describe afferent information reaching the cerebellum through the spinocerebellar pathways. This information is essential for smooth motor coordination - Interoception is a term referring to unconscious afferent signals involved in visceral reflexes. 3. Somatic sensory pathways Two major pathways are involved in somatic sensory perception. They are the dorsal column–medial lemniscal pathway and the spinothalamic (ventrolateral) tract. They have common traits:  - Both share 1st, 2nd & 3rd order sensory neurons - The Somas of 1st order neurons occupy dorsal root ganglia - Somas of 2nd order neurons occupy CNS grey matter on the same side as the 1st order. - 2nd order cross the midline and then ascend to terminate in the thalamus. - 3rd order neurons project from thalamus to somatosenroy cortex - Both pathways are somatotopic: an orderly map of body parts can be identified experimentally in the grey matter at each of the three loci of fibre termination. - Synaptic transmission of primary – secondary & secondary – tertiary neurons can be modulated by other neurons Two major pathways are involved in somatic sensory perception. They are the dorsal column–medial lemniscal pathway and the spinothalamic (ventrolateral) tract. They have common traits: - Both share 1st, 2nd & 3rd order sensory neurons - The Somas of 1st order neurons occupy dorsal root ganglia - Somas of 2nd order neurons occupy CNS grey matter on the same side as the 1st order. - 2nd order cross the midline and then ascend to terminate in the thalamus. - 3rd order neurons project from thalamus to somatosenroy cortex  - Both pathways are somatotopic: an orderly map of body parts can be identified experimentally in the grey matter at each of the three loci of fibre termination. - Synaptic transmission of primary – secondary & secondary – tertiary neurons can be modulated by other neurons 4. Dorsal column medial lemniscus pathway (DCML) Rapid recap from last year: The dorsal column-medial lemniscal pathway (DCML) carries the sensory modalities of fine touch (tactile sensation), vibration and proprioception. Its name arises from the two major structures that comprise the DCML. In the spinal cord, information travels via the dorsal (posterior) columns. In the brainstem, it is transmitted through the medial lemniscus. There are three groups of neurones involved in this pathway – first, second and third order neurones. First Order Neurones The first order neurones carry sensory information regarding touch, proprioception or vibration from the peripheral nerves to the medulla oblongata. There are two different pathways which the first order neurones take: Signals from the upper limb (T6 and above) – travel in the fasciculus cuneatus (the lateral part of the dorsal column). They then synapse in the nucleus cuneatus of the medulla oblongata.  Signals from the lower limb (below T6) – travel in the fasciculus gracilis (the medial part of the dorsal column). They then synapse in the nucleus gracilis of the medulla oblongata. Second Order Neurones The second order neurones begin in the cuneate nucleus or gracilis. The fibres receive the information from the preceding neurones, and delivers it to the third order neurones in the thalamus. Within the medulla oblongata, these fibres decussate (cross to the other side of the CNS). They then travel in the contralateral medial lemniscus to reach the thalamus. Third Order Neurones Lastly, the third order neurones transmit the sensory signals from the thalamus to the ipsilateral primary sensory cortex of the brain. They ascend from the ventral posterolateral nucleus of the thalamus, travel through the internal capsule and terminate at the sensory cortex. …………End of recap of last year……………………………………………………………………………………………… a. Brief definition and receptors associated to DCMLS The dorsal column–medial lemniscal system (DCMLS), which includes the fasciculus gracilis, fasciculus cuneatus, and medial lemniscus, relays: - discriminative (fine) tactile sense, - flutter-vibratory sense, - proprioception (position sense) to consciousness. Tactile sensation is divisible into nondiscriminative (crude) touch and discriminative (fine) touch. Nondiscriminative (crude) touch is transmitted via the ALS. Stereognosis (ability to recognise a 3D object) and two-point discrimination rely on fine discrimina tive tactile sense and are relayed to consciousness via the DCMLS. Conscious proprioception may be categorized into static and dynamic proprioception. - Static proprioception (static position sense) is the awareness of the position of a motion less body part such as a limb, - dynamic proprioception (kinesthetic sense) is the awareness of movement of a body part, and balance.  b. First order neuron The receptors that transmit discriminative (fine) touch, pro prioception, vibratory sense, and pressure sense, informa tion to consciousness consist of: - free nerve endings responding to touch, pressure, and proprioception in the skin, muscles, and joint capsules; - tactile (Merkel’s) discs responding to touch and pressure in the skin; - peritrichial endings stimulated by touch of the hair follicles; - Meissner’s corpuscles activated by touch of the skin; - Pacinian corpuscles stimulated by touch, pressure, vi bration, and proprioception in the deep layers of the skin, and in visceral structures; - Ruffini end organs respond to stretching of the collagen bundles in the skin or joint capsules; - Muscle spindles stimulated by muscle stretch; - GTOs stimulated by muscle tension exerted on tendons. These first order pseudounipolar neurons, whose cell bodies are located in the dorsal root ganglia, send periph eral processes to somatic or visceral structures. Most of these peripheral processes are medium-size type Aβ and large- size type Aα fibers. Upon being stimulated, the peripheral processes transmit the sensory information to the spinal cord by way of the central processes of the pseudounipolar neurons, which enter the spinal cord at the dorsal root entry zone via the medial division of the dorsal roots of the spinal nerves. Somatotopic organization Somatotopic organization of fibers of the dorsal column-medial lemniscal pathway becomes evident beginning at the spinal cord level. As the central processes of the pseudounipolar neurons enter the spinal cord at successively higher levels, they are added from medial to lateral. The fibers carrying sensation from the sacral dermatomes occupy the most medial aspect of the dorsal column, whereas the fibers carrying sensation from the lumbar, thoracic, and cervical dermatomes are added sequentially more laterally. As the sacral fibers ascend in the upper half of the spinal cord, they rotate from the most medial position (next to the spinal cord midline) to the most dorsal aspect of the dorsal column. The fibers that relay tactile sensation occupy a more dorsal region of the dorsal columns, whereas the fibers that relay proprioception occupy a more ventral region of the dorsal columns. The fibers that relay tactile sensation terminate in the lower region of the dorsal column nuclei, whereas the fibers that relay proprioception ascend further up to terminate in the upper re gion of the dorsal column nuclei. 85–90% of the fibers ascending in the dorsal columns consist of the central processes of mechanoreceptor neurons (whose cell bodies are housed in the dorsal root ganglia). The remaining 10–15% of fibers ascending emerge from a unique group of cell bodies of second order neurons that reside not in the dorsal root ganglia (as those of the mechanoreceptors), but instead, in the dorsal horn of the spinal cord. These neurons relay nociceptive impulses arising from the pelvic viscera and lower part of the GI tract. Thus, in addition to mechanoreceptor input, the fasciculus gracilis also carries a minor but distinct group of fibers relaying visceral nociception to the nucleus gracilis in the medulla. FG/NG: The central processes that enter the spinal cord below the sixth thoracic (T6) level include the lower thoracic, lumbar, and sacral levels. They bring information from the lower limb and lower half of the trunk. The central processes enter the ipsilateral fasciculus gracilis (FG) and ascend to the medulla to terminate in the ipsilateral nucleus gracilis (NG). FC/NC: The central processes that enter the spinal cord at approx imately the sixth thoracic (T6) level and above bring infor mation from the upper thoracic and cervical levels; that is, from the upper half of the trunk and upper limb. These cen tral processes enter the ipsilateral fasciculus cuneatus (FC) (L. cuneus, “wedge”) and ascend to the medulla to synapse with second order neurons in the ipsilateral nucleus cuneatus (NC). C1 does ont have any sensory fibers. c. 2nd order neurons The first order fibers terminating in the nucleus gracilis (NG) and nucleus cuneatus (NC) synapse with second order neu rons whose cell bodies are housed in these nuclei, in the posterior medulla. The fibers of the second order neurons emerging from the dorsal column nuclei form the internal arcuate fibers as they curve ventromedially in the caudal medullary tegmentum, through the reticular formation to the opposite side. These fibers ascend as the medial lemniscus in the caudal part of the medulla, cranial to the prominent pyramidal (motor) decussation, to synapse with third order neurons in the VPL nucleus of the thalamus. The axons of second order neurons arising from the NG (relaying sensation from the lower limb and lower trunk) occupy the ventral half of the medial lemniscus, whereas the second order axons arising from the NC (relaying sensation from the upper limb and upper trunk) occupy the dorsal half of the medial lemniscus. At pontine levels, the medial lemniscus shifts orientation with the fibers representing the legs are dorsolaterally and the head ventromedially 🡪 90 rotation of the fibers. The fibers of second order neurons originating from the nucleus cuneatus terminate in the medial aspect of the VPL nucleus of the thalamus, whereas the fibers emerging from the nucleus gracilis terminate in the lateral aspect of the VPL. d. 3rd order neurons The VPL nucleus of the thalamus houses two distinct popu lations of neurons, which process sensory input relayed by the DCML pathway: (1) the cell bodies of the third order neu rons of the DCML pathway, and (2) local circuit interneurons. The third order neurons (thalamocortical cells) give rise to thalamocortical fibers that ascend in the posterior limb of the internal capsule and the corona radiata to terminate in the primary (SI) and secondary (SII) somatosensory cor tices. The SI resides in the postcentral gyrus (which corre sponds to Brodmann’s areas 3a, 3b, 1, and 2, of the parietal cortex/lobe). 5. Anterolateral system (spinothalamic and spinoreticular) Revisions from Y1…………………………………………………………………………………………………………………………… Spinothalamic system: The anterolateral system consists of two separate tracts:  Anterior spinothalamic tract – carries the sensory modalities of crude touch and pressure. Lateral spinothalamic tract – carries the sensory modalities of pain and temperature. Much like the DCML pathway, both tracts of the anterolateral system have three groups of neurones. First Order Neurones The first order neurones arise from the sensory receptors in the periphery. They enter the spinal cord, ascend 1-2 vertebral levels, and synapse at the tip of the dorsal horn – an area known as the substantia gelatinosa. Second Order Neurones The second order neurones carry the sensory information from the substantia gelatinosa to the thalamus. After synapsing with the first order neurones, these fibres decussate within the spinal cord, and then form two distinct tracts: Crude touch and pressure fibres – enter the anterior spinothalamic tract. Pain and temperature fibres – enter the lateral spinothalamic tract. Although they are functionally distinct, these tracts run alongside each other, and they can be considered as a single pathway. They travel superiorly within the spinal cord, synapsing in the thalamus. Third Order Neurones The third order neurones carry the sensory signals from the thalamus to the ipsilateral primary sensory cortex of the brain. They ascend from the ventral posterolateral nucleus of the thalamus, travel through the internal capsule and terminate at the sensory cortex. Spinoreticular pathway Originate in laminae V-VII and terminates at levels of brainstem: it is not somatotopically arranged. - Functions: o Arouse cerebral cortex 🡪 induce/maintain waking state o Report to limbic cortex nature of stimulus 🡪 emotional response can be pleasurable or aversive …………end of revisions…………………………………………………………………………………………………………  The anterolateral system thermal, itch and nondiscriminatory (ALS) transmits nociceptive, thermal, itch, and nondiscriminatory (crude) touch information to higher brain centers generally by sequence of three neurons and interneurons. The neuron sequence consists of: 1) First order neuron (pseudounipolar neuron)whose cell body is located in a dorsal root ganglion. It transmits sensory information from peripheral structures to the dorsal (posterior) horn of the spinal cord. 2) Second order neuron whose cell body is located within the dorsal horn of the spinal cord, and whose axon usually decussates and ascends: o in the direct pathway of the ALS (spinothalamic tract) to synapse in the contralateral thalamus, and sending some collaterals to the reticular formation; o in the indirect pathway of the ALS (spinoreticular tract) to synapse in the reticular formation, and sending some collaterals to the thalamus; or o as spinomesencephalic, spinotectal, spinohypothalamic, or spinobulbar (spinoolivary) fibers to synapse in several brainstem nuclei and the hypothalamus. 3) Third order neuron whose cell body is located in the thalamus, and whose axon ascends ipsilaterally to terminate in the somatosensory cortex or other cortical areas.  The anterior spinothalamic tract contains infos of light touch and pressure. Fibers first enter in the dorsal root ganglion (1st neuron) and then into the spinal cord at the level of the posterior horn in grey matter. Here they give rise to collaterals, which ascend or descend one or two vertebral levels via Lissauer’s tract and then synapse with secondary neurons in either the substantia gelatinosa or the nucleus proprius of the posterior gray column. These secondary neurons are called tract cells. The remaining axon, entered in the dorsal horn, has here the 2nd neuron and fibers synapse in laminae I-II. They decussate through the white commissure to reach the contralateral anterior funiculus. Fibers ascend, reaching the medulla oblongata and, as the spinal or anterolateral lemniscus util they arrive in the thalamus, ALO if the VPL. At the end, fibers will enter the posterior limb of the internal capsule, through the corona radiata and reach the posterior central gyrus of the cerebral cortex. In the lateral portion of the white matter there is the lateral spinothalamic tract, that can be subdivided into medial and lateral parts, having different contents. Lateral division - neo-spinothalamic tract: Laterally are carried informations of temperature and acute pain, which needs to maintain the discriminative pathway, therefore these fibers, forming the neo-spinothalamic tract, have the same ascending pathway of the anterior spinothalamic tract. Their location though is different, since they’re always part of the lateral spinothalamic tract, so aren’t located in the anterior funiculus, but in the lateral funiculus (they’re in continuity with one another). At the end fibers reach the VPL nucleus of the thalamus and give rise to collaterals also to intralaminar thalamic nuclei. Medial division - paleo-spinothalamic tract: Medially are carried informations of temperature and emotional pain, that is highly modulated and receive other attributions, forming the so called paleo-spinothalamic tract. a. First order neuron Receptors that transmit nociceptive information consist of high-threshold free nerve endings ramifying near the external surface and internal environment of the organism. These are dendritic arborizations of small, pseudounipolar, first order neurons whose soma are in a dorsal root ganglion. The peripheral processes of these pseudounipolar neurons consist of two main types of fibers: - Thinly myelinated Aδ (fast-conducting) fibers, which relay sharp, short-term, well-localized pain (such as that resulting from a pinprick). - Unmyelinated C (slow-conducting) fibers, which relay dull, persistent, poorly-localized pain (such as that result ing from excessive stretching of a tendon). The central processes of these pseudounipolar neurons enter the spinal cord at the dorsal root entry zone, via the lateral division of the dorsal roots of the spinal nerves, and upon entry collectively form the dorsolateral fasciculus (tract of Lissauer), which is present at all spinal cord levels. These central processes bifurcate into short ascending and descending branches within the dorsolateral fasciculus (tract of Lissauer). Therefore, although stimulation of the peripheral endings of fibers carried by one spinal nerve may enter the spinal cord at a specific spinal level, collaterals of the ascending and descending branches spread the signal to neighboring spinal levels above and below the level of entry. b. Second order neurons The cell bodies of the second order neurons transmitting nociception reside in the dorsal horn of the spinal cord. The axons of these second order neurons course in either the direct (spinothalamic) or indirect (spinoreticular) pathways of the ALS. 1) Direct pathway of the anterolateral system – spinothalamic Most Aδ fibers participate in the direct pathway of the ALS. Type Aδ fibers of first order neurons synapse primarily with second order neurons in lamina I (posteromarginal nucleus, or zone) and lamina V (reticular nucleus) of the spinal cord gray matter. However, many first order neurons synapse with spinal cord interneurons that are associated with reflex motor activity. Most of the axons of the second order neurons flow across the midline to the contralateral side of the spinal cord in the anterior white commissure, forming the spinothalamic tract. The spinothalamic tract transmits not only nociceptive input, but also thermal, itch and nondiscriminative (crude) touch input to the contralateral VPL nucleus of the thalamus. Since the spinothalamic tract (direct pathway of the ALS: spinal cord → thalamus) is phylogenetically a newer pathway, it is referred to as the neospinothalamic pathway. The spinothalamic tract consists of two anatomically distinct tracts: - the lateral spinothalamic tract (located in the lateral funiculus) - and the very small anterior spinothalamic tract (located in the anterior funiculus). When these two tracts unite in the brainstem they form the spinal lemniscus. 2) Indirect pathway of the anterolateral system – spinoreticular Most C fibers participate in the indirect pathway of the ALS. Type C fibers of first order neurons terminate on in terneurons in laminae II (substantia gelatinosa) and III of the dorsal horn. Axons of these interneurons synapse with second order neurons in laminae V–VII. These axons form the more prominent ipsilateral and smaller contralateral spinoreticular tracts. The spinoreticular tracts transmit nociceptive, thermal, and nondiscriminatory (crude) touch signals from the spinal cord to the thalamus indirectly, by forming multiple synapses in the reticular formation prior to their thalamic projections. Since the multisynaptic spin oreticular tract (indirect pathway of the ALS: spinal cord → reticular formation → thalamus) is phylogenetically an older pathway, it is referred to as the paleospinothalamic pathway. It transmits slow, poorly-localized, dull pain input. 3) Additional pathways In addition to the spinothalamic and spinoreticular tracts, the ALS also containsm the spinomesencephalic, spinotectal, spinobulbar (spinoolivary), and spinohypothalamic fibers The spino mesencephalic pathway conveys also nociceptive information but does not end in the cerebral cortex, it stops in the periacqueductal gray in the mesencephalon. In these nuclei desceding pathways originate and so play a role in pain modulation, acting as an analgesic system. Spinocervicothalamic tract: This tract is also made of fibers that carry pain and temperature, but NOT as a part of the spinothalamic tract. Involves the first neuromers of the cervical portion of the spinal cord. Some of these acending fibers can be modulated at the lateral cervical nucleus where they synapse (so there is an intermediate station in the brainstem between the spinal cord and the thalamus). From here the second order neurons are added to the fiber bundle forming the medial lemniscus. They contain proprioceptive, pain, and thermal information. Therefore also in the medial lemniscus there is the possibility to receive some pain stimuli that reach the cortex. So: 1. Dorsal root ganglion to lamina IV (III – V) 2. Ascending in the dorsolateral column, to the lateral cervical nucleus (in the upper cervical part) 3. Decussation through the medial lemniscus 4. VPL nucleus in the thalamus 5. Primary somatosensory cortex  c. 3rd order neurons The VPL nucleus gives rise to fibers that course in the pos terior limb of the internal capsule and in the corona radiata to terminate in the postcentral gyrus (primary somatosen sory cortex, SI) of the parietal lobe of the cerebral cortex. The primary somatosensory cortex (SI) consists of the post central gyrus of the parietal lobe, which corresponds to Brodmann’s areas 3a, 3b, 1, 2. Somatotopism of the lateral division 1. Spinal cord (spinothalamic tract): cranio-caudal medio-lateral 2. Brainstem (spinal lemniscus): cranio-caudal medio-lateral 3. Thalamus (VPL nucleus): cranio-caudal medio-lateral 4. Cerebral cortex: cranio-caudal medio-lateral, the same of the medial division  6. Pain reception The discriminative information ascends very quickly while the pain info is processed receving collaterals through interneurons that integrate information regading both the stimulus itself and the pain associated to it, but also integrating the different pain coming from different receptors travelling with different types of fibers. In the end we have in the picture as an example, the integration ofAα, Aβ (sensory information without pain attribution) Adelta, C fibers through the same interneuron in the spinal cord. At this level we have the possibility to modulate the information coming from the periphery, and to carry on the pain attribution to the upper centers or just the sensory information, resulting in inhibition or amplification of the pain. Cortical and subcortical descending pathways work also in the modulation of the pain signal with an integration through interneurons. A-delta (fast pain) are going to lamina 1 and synapse there, from there they either project or integrate with other neurons in lamina 2 C fibres arrive to lamina 2 and synapse with a large interneuron that receives a collateral from A-delta and also A-alpha and A-beta fibres - an integration between touch and pain fibres. Through this system there is the possibility to inhibit the projection neuron and stop the ascending system at the same level of the spinal cord  7. Gated theory circuit that reduced the pain sensation The pathways carrying discriminative info and pain are separated but converge on the same interneuron in the dorsal horn, connected to a projection neuron: the action of the interneuron is inhibitory to the projection one. The inhibitory interneurons are spontaneously active (normally “close” the gate), but in the picture the C fiber inhibits the inhibitory interneuron= inhibition + inhibition🡪excitation of the projection neuron that is allowed to carry the pain signal to upper centers. The origin of the pain is not at the level of the receptor but on the projection neuron! In this theory the gates are on the projection neuron that is “closed” or “open” depending on the action of the inhibitory interneurons (if they are active or inhibited). Gate open🡪inhibition of the substantia gelatinosa (inhibitory interneurons). Gate closed🡪prevail of the tactile fibers that activate the inhibitory interneurons. Large diameter fibers (for e.g., touch) close the gate🡪 related to agopuncture technique In sum, Modulation of pain by interactions between 4 neurons in the dorsal horn of the spinal cord: ✔ A-alpha/A-beta fibers – myelinated tactile efferents: enter the ganglion, then grey matter. The second order neuron is at the level of the lamina IV/V. Then, the projection neuron will give rise to the spinothalamic tract. Will stimulate the inhibitory interneuron (which will inhibit the projection neuron – mechanical information will pass but pain might not) and also the projection neuron ✔ C fibers – unmyelinated nociceptor afferents: will inhibit an inhibitory interneuron. Along with Adelta: synapse with the second order neuron and also the interneuron – it is also a projection neuron. Important to understand if is inhibitory or excitatory ✔ Projection neuron: origin of pain – if it allows the passage, the pain attribution will pass. Otherwise, it won’t. The projection neuron transmits mechanical information, but is it considered pain or not? It is considered pain, if, from that area, there is also the arrive from other information (transported by other fibres), that enter there and we have to see if these are prevalent or not. If yes, the mechanical stimulus will be sent with the pain too. If they are not that prevalent, they wont ✔ Inhibitory interneurons: substantia gelatinosa, spontaneously active Analgesic descending pathways: Descending fibers carrying information from higher centers can inhibit the projection neurons stopping or attenuating the painful information. Fibers able to do so come from the periacqueductal gray, reticular formation, nucleus raphe. They act directly on the inhibitory interneurons of the substantia gelatinosa, by pre or post synaptic inhibition (blocking the transmission of the pain fiber to the projection neuron). We have specific substances that act on this analgesic system🡪 endocannabinoids, opioids, serotonin, norephinephrine There are mainly two systems: 1. Periaqueductal grey in the midbrain: Oppioidopeptidergic (ENK: PAG, periaqueductal grey); periaqueductal grey in the midbrain → descends through the pons and medulla → Activates the nucleus raphe magnus (NRM) in the medulla (serotonergic)→ Crosses the midline → Activates the inhibitory interneuron in the substantia gelatinosa with serotonin (note that serotonin activity depends on the receptor) 2. Dorsolateral pontine reticular formation (DPRF): the descending fibers are crossing. The reticular formation is involved in both ascending and descending pathways of pain. From the pons, there is a descending system that both stops in the raphe Magnus and descends directly. Noradrenergic (DPRF) → substantia gelatinosa (ENK, dinorphin). Pain control and interpretation We have also descending pathways involved in pain control from hypothalamus and hypophysis, in order to give an interpretation to the pain, depending what is the state of the body at the moment. Many areas are in fact involved in adding the emotional aspects and relate the pain to past experiences. In particular the cingulate gyrus is responsible for attributing emotions to pain. Example: in a state of anxiety as the body/ brain is focused so much on something else the pain is not considered and the projectory neuron is inhibited or completely shut down. Other cortical areas: - Post-central gyrus: pain related to past experiences – final role is the integration of all the signals Insular gyrus: visceral pain – autonomic response 8. Unconcious pathways Most of the proprioceptive information does not reach conscious levels and instead is transmitted directly to the cerebellum. Instead, it is transmitted directly to the cerebellum via the ascending somatosensory cerebellar pathways without projecting to the thalamus or the cerebral cortex. The pathways include: the dorsal (posterior) spinocerebellar tract, the cuneocerebellar tract, the ventral (anterior) spinocer ebellar tract, and the rostral spinocerebellar tract. a. Dorsal spinocerebrellar tract The primary function of the dorsal spinocerebellar tract is to relay proprioceptive input from the neuromuscular spindles and GTOs of the ipsilateral trunk and lower limb, to the cerebellum First order neurons (pseudounipolar neurons) whose cell bodies are housed in the dorsal root ganglia send their peripheral processes to the skin, muscles, tendons, and joints. They perceive proprioceptive information, which is then transmitted to the spinal cord by their central processes. These central processes join the medial division of the dorsal roots of the spinal nerves to synapse in the nucleus dorsalis (Clark’s column, lamina VII of spinal cord levels C8 to L2, 3) at their level of entry. Clark’s column houses the cell bodies of second order neurons whose axons form the dorsal spinocerebellar tract, which ascends ipsilaterally in the lateral funiculus of the spinal cord. When this tract reaches the brainstem it joins the restiform body (of the inferior cerebellar peduncle), and then passes (as “mossy fibers”) into the vermis of the cerebellum. The dorsal spinocerebellar tract relays proprioceptive information directly to the cerebellum where this information is processed; it plays an important role in the fine coordination of movements of individual lower limb muscles or synergistic muscles controlling movement of the same joint and in the maintenance of posture. b. Cuneocerebrellar tracts Proprioceptive sensory information from the neck, upper limb, and upper half of the trunk enters at spinal cord segments C2 to T5. The central processes of the pseudounipolar first order neurons ascend in the fasciculus cuneatus and terminate in the external (accessory) cuneate nucleus – the nucleus dorsalis of Clark ho mologue at cervical levels above C8. The axons of the second order neurons, whose cell bodies reside in the accessory (lateral) cuneate nucleus, form the cuneocerebellar tract. This tract is referred to as the neck and upper limb counterpart of the dorsocerebrallar tract. Fibers of the cuneocerebellar tract join the restiform body (of the inferior cerebellar peduncle) and then enter the anterior lobe of the cerebellum ipsilaterally. c. Ventral (anterior) spinocerebellar tract The ventral (anterior) spinocerebellar tract relays proprioceptive information from the muscle spindles and GTOs of the trunk and lower limb. It functions in the coordination of mouvement and maintainance of posture. First order neurons (pseudounipolar neurons) transmit sensory input to laminae V–VII of the lumbar, sacral, and occygeal spinal cord levels, where they terminate and synapse with second order neurons. The axons of these second order neurons, known as spinal border cells, form the ventral (anterior) spinocerebellar tract, which decussates in the anterior white commissure and ascends in the lateral funiculus of the spinal cord to the medulla. The ventral spinocerebellar fibers ascend to the rostral pons and then descend to join the superior cerebellar peduncle to pass as “mossy fibers” into the cerebellum. These fibers then decussate again to their actual side of origin within the cerebellum to end in the vermis of the cerebellum’s anterior lobe. d. Rostral spinocerebrellar tract Proprioceptive information from the head and upper limb is transmitted to C4–C8 spinal cord levels. The central processes of first order neurons synapse with second order neurons whose cell bodies reside in lamina VII of the dorsal horn. The fibers of the second order neurons form the primarily uncrossed rostral spinocerebellar tract, the head and upper limb counterpart of the ventral spinocerebellar tract. These fibers join the restiform body (of the inferior cerebellar peduncle) to enter the cere bellum. Additionally, some fibers pass into the cerebellum via the superior cerebellar peduncle. This tract plays a role in movement of the head and upper limb. General sensation from the head comes from the trigeminal nerve (V): it carries pressure, pain, temperature, touch from skin and mucous membrane of the face, muscle spindles and joint receptors (temporo-mandibular joint). Mainly, the first order neurons are located at the level of the Gasser’s ganglion, located into the middle cranial fossa close to the cavernal sinus. At the level of the periphery is made from 3 divisions that that have their cell bodies in the Gasser’s ganglion, with a specific somatotopism. Eventually the fibers end in 3 different nuclei and synapse with second order neurons: one in the medulla, one in the pons and one in the midbrain: - The one of the medulla is called spinal nucleus because there is a continuation in the spinal cord substantia gelatinosa: contains info about temperature, nociception and non discriminative touch. This nucleus is lateral to the nuclei gracilis and cuneatus. - In the pons we have the main sensory nucleus with discriminative touch and pressure - in the mesencephalic nucleus the info carried is proprioception. Presence of some first order neurons! (bypass the trigeminal ganglion) Some few somatosensory fibers form the face are collected from the facial, glossopharyngeal and vagus nerve, that end in the trigeminal nerve nuclei. From the three trigeminal sensory nuclei there is an ascending system (trigeminothalamic) divided into a ventral and dorsal division (two pathways): - Ventral, the main one, located immediately posterior to the medial lemniscus, ascending together with it and contralaterally. The trigeminal lemniscus is annexed to the medial lemniscus when ascending, they form a main group of bundles called the superior lemniscus. When reaching the thalamus, the trigeminal lemniscus enters ventrally and the medial lemniscus, dorsally. So, the superior lemniscus is formed by the trigeminal lemniscus and the medial lemniscus, but the division is maintained when entering the thalamus - Dorsal, close to the ventricle – ipsilateral Note that all information is bilateral! Both pathways are reaching the ventral postermedial nucleus of the thalamus (synapse with third-order neuron). From here information ends in the post-central gyrus of the somatosensory cortex.