Responsible for a bunch of fairly important things including touch or tactile discrimination, vibration, pressure, limb positioning or proprioception, pain, temperature.
* The nervous system consists of discrete systems for each of the sensory modalities (touch, vision, hearing, taste, smell)
* Each functional system involves several CNS regions that carry out different types of information processing
* Identifiable pathways link the components of a functional system
* Each part of the brain projects in an orderly fashion onto the next, creating sensory (e.g. topographic) maps. Neural maps not only reflect the position of receptors on a sensory surface, but also their density
* Functional systems on one side of the body generally respond/control the other side of the body
* Specific receptor neurons located in skin or joints receive stimuli
* Information is carried to brain via the spinal cord, brainstem, thalamus, to the post central gyrus of the parietal lobe, which in turn project to higher order cortical areas
* Projections are topographic with respect to body region, and the amount of cortical space allocated to various body parts is proportional to the density of sensory receptors in that area
<figure><figcaption class="big">Touch and pain have different routes to the brain</figcaption><img src="figs/Neuroscience5e-Fig-09.01-0_e315cfe.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 9.1</figcaption></figure>
We’ve already become aware that the dorsal root ganglia contain sensory neurons that act as sensory receptors for the body with the cell body located in the ganglion and processes extending to the sensory periphery— e.g. this mechanosensory afferent fiber connected to your index finger, or a proprioceptive neuron sensing internal muscle stretch connected to your knee joint for the myotactic reflex that we’ve discussed previously.
In this inset you see both mechanosensory and pain sensitive fibers connected to the finger— notice that these are coming from two different neurons (red and blue) and the ascending process from the DRG neurons course through the spinal cord to higher brain regions through different routes. *anterolateral tract vs dorsal column*. More on this later.
<figure><figcaption class="big">Types of somatosensory afferents linking receptors to the CNS</figcaption><img src="figs/Neuroscience5e-Tab-09.01_copy_653cef2.jpg" height="400px"><figcaption>Neuroscience 5e Table 01</figcaption></figure>
## Slowly adapting and rapidly adapting mechanoreceptors respond differently to stimulation
<figure><img src="figs/Neuroscience5e-Fig-09.04-0_b85b14e.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 9.4</figcaption></figure>
Note:
Another type of somatosensory afferent variability I mentioned was rate of adaptation– this figure highlights this difference where if we were performing extracellular electrode recordings close to somatic sensory we find that some types adapt slowly, with sustained spiking as a stimulus stays on, whereas others adapt rapidly with their spiking activity strong at the beginning of the stimulus but quiet as the stimulus is maintained.
* Sensory feedback information about **self**. Where are my limbs and other body parts?
* Muscle spindles– sensory organ inside muscles. Consists of 'intrafusal' muscle fibers enveloped by fast Group Aα (Ia) sensory neuron afferents. Signals present muscle stretch.
* Golgi tendon organs– sensory organ between muscle fiber and tendon. Consists of connnective tissue enveloped by fast Group Aα (Ib) sensory neuron afferents. Signals present muscle force.
* Stimuli applied to skin, deforms or changes the nerve endings, produces a receptor potential that triggers an action potential
* Quality of stimulus (what it represents and where it is) is determined by the relevant receptor and the afferent neuron’s targets in the brain
* Quantity or strength of stimulus is determined by the rate of action potential discharge
Note:
---
## Somatosensory receptors
<figure><img src="figs/Neuroscience5e-Fig-09.02-0_e1a0b72.jpg" height="500px"><figcaption>Neuroscience 5e Fig. 9.2</figcaption></figure>
Note:
The sensation of touch, pain, or temperature all starts with specialized receptors and nerve endings in the skin. In all cases ion channels open on the receptor neuron ending that can depolarize and initiate an AP with a sufficiently strong stimulus.
- example in this fig looks like a pacinian corpuscle
-piezo type mechanosensitive ion channel component 2
-protein encoded by this gene contains more than thirty transmembrane domains and likely functions as part of mechanically-activated (MA) cation channels
-channels serve to connect mechanical forces to biological signals
piezo
: greek for push
Piezoelectric Effect
: ability of some materials to generate an electric charge in response to applied mechanical stress
: reversible: mechanical stress <–> electricity
: gas stoves, cigarette lighters
: piezoelectric ceramics (Lead zirconate titanate or PZT Pb[Zr~x Ti~1-x ]O~3 ) and single crystal materials (gallium phosphate, quartz, tourmaline)
* Provide information about touch, pressure, vibration, and cutaneous tension
* Four major types of encapsulated mechanoreceptors:
* Merkel’s disks
* Meissner’s corpuscles
* Ruffini’s corpuscles
* Pacinian corpuscles
* Called low-threshold mechanoreceptors because even weak stimulation causes them to fire action potentials. Innervated by large myelinated axons (type Aβ fast)
| conduction velocity |40-65 m/s | 35-70 m/s | 35-70 m/s | 35-70 m/s |
| sensory function | form and texture perception | motion detection, grip control | tangential force, hand shape, motion direction | perception of distant events through transmitted vibrations, tool use |
| best threshold for rapid indentation | 8 µm | 2 µm | 40 µm | 0.01 µm |
| mean threshold for rapid indentation | 30 µm | 6 µm | 300 µm | 0.08 µm |
</div>
<!-- <figure><img src="figs/Neuroscience5e-Tab-09.02_1587a04.jpg" height="100px"><figcaption>Neuroscience 5e Table 2</figcaption></figure> -->
Note:
Two broad classes based on receptive field area, innervation density-- both classes (ones with small receptive fields vs large receptive fields) have subtypes that have either sustained activity upon depression or transient activity just at when the stimulus is changin
- receptive fields as measured with rapid 0.5 mm indentation
- table after K.O. Johnson 2002
Work
: *W* = *Fs*, force*displacement (N-M)
: joules newton-meters, N–M
: force over time
: no displacment, no work
: no work in direction orthongonal to displacement
-piezo type mechanosensitive ion channel component 2
-protein encoded by this gene contains more than thirty transmembrane domains and likely functions as part of mechanically-activated (MA) cation channels
-channels serve to connect mechanical forces to biological signals
Each dot represents an action potential recorded in a single mechanosensory afferent fiber.
Horizontal line of dots in the raster plot represents the pattern of activity in the afferent when moving the pattern across the finger. The pattern position is then displaced slightly by a small distance and then the pattern is moved again and the spike pattern is displayed on the next row.
Individual Braille dots can be distinguished in the pattern of Merkel afferent neural activity
---
## Differences in mechanosensory discrimination across the body surface
* The accuracy of our sense of touch is not the same all over the body
* Can use two-point discrimination tests to show this
* Fingers can distinguish things 2 mm apart, forearms 40 mm apart
* Mechanosensory receptors are more numerous in finger tips and have smaller receptive fields
* Doesn't explain everything about ability to discriminate two points. The CNS is also involved with discrimination. Two point thresholds vary with practice, and depend on the stimulus
* Crickets sense of touch comes from air currents moving sensory hairs.
* Left: Specific hairs only fire if blown a certain direction.
* Right: summation of recordings from a single neuron whose hair has been blown from every direction. It only fires an AP when it is moved in a certain direction.
* The cell somas of mechanosensory axons are located in the dorsal root ganglion (DRG). One on each side of the spinal cord, one for each segmental spinal nerve
* DRG neurons called first-order because they initiate the sensory process
* All sensory axons cross the midline once
* All map to primary somatic sensory cortex, located in the postcentral gyrus
* Mechanoreceptors and proprioception receptors use the dorsal-column-medial lemniscus pathway to get to brain
* Pain and temperature use spinothalamic (anterolateral pathway)
Note:
---
## Dorsal column-medial lemniscus system
* Dorsal root ganglion neurons– first order, initiate process
* Contains info from mechanoreceptors concerned with tactile discrimination or proprioception
* Upon entering spinal cord, axons bifurcate into ascending and descending branches, which in turn send out collateral branches to several spinal segments
* Some branches go to ventral horn of the cord and synapse on neurons that are part of the reflex system
* The major branches of dorsal root ganglion neurons are ascending and go up the dorsal columns of the spinal cord ipsilaterally
* They terminate in the gracile and cuneate nuclei (dorsal column nuclei) in the caudal (posterior) medulla
* Axons are organized such that lower limbs are mapped medially (gracile nucleus) and the upper limbs, trunk, and neck in the cuneate nucleus
* Axons from both nuclei cross the midline in the medulla and send projections to the somatic sensory portion of the thalamus, the ventral posterior lateral nucleus (VPL). Cuneate axons terminate in medial VPL, gracile projections terminate in lateral VPL
Upper and lower body use slightly different pathways.
**Cross in the medulla**
</figcaption><img src="figs/Neuroscience5e-Fig-09.08-1R_63fefc0.jpg" height="500px"><figcaption>Neuroscience 5e Fig. 9.8</figcaption></figure>
Note:
---
## Trigeminal tract
* Information about the face takes a different route to the thalamus
* Trigeminal nerve (cranial nerve V, three subdivisions: ophthalmic, maxillary, and mandibular)
* Enters the brainstem at the level of the pons and terminates in the trigeminal brainstem complex. This complex has two main components, the principal nucleus (mechanosensory stimuli) and the spinal nucleus (pain and temp)
* Crosses midline in the pons and ascends to thalamus
Note:
---
## Trigeminal pathway (face)
<figure><figcaption class="big">
Info from head and face.
**Crosses in pons midbrain**
</figcaption><img src="figs/Neuroscience5e-Fig-09.08-2R_c455315.jpg" height="500px"><figcaption>Neuroscience 5e Fig. 9.8</figcaption></figure>
* Ventral posterior lateral nucleus (VPL) receives projections from the medial lemniscus carrying all somatic sensory information from the body and posterior head
* Ventral posterior medial nucleus (VPM) receives axons from the trigeminal info from the face
* VPC contains a complete representation of the body
…and is the gateway for routing information into the cerebral cortex. It contains a number of different nuclei and subdivision that take information from other brain regions including the brain stem and sends to appropriate primary sensory or higher order regions of the cerebral cortex.
Note areas 4 (primary motor cortex), 1,2,3 (primary somatosensory cortex), area 17 (primary visual cortex), area 18 (secondary visual cortex), area 41,42 (primary auditory cortex, also part of 22)
*Comparative localization teachings of the cerebral cortex in their principles, illustrated on the basis of Zellenbaues. Leipzig, Johann Ambrosius Barth Verlag, 1909 . 2nd edition, 1925. English translation by Laurence J. Garey: Localisation in the Cerebral Cortex by Korbinian Brodmann. Smith-Gordon, 1994; new impression: Imperial College Press., 1999*
*area 44,45 Broca's areas*
*area 39,40,22 wernicke's areas*
*area 43 gustatory cortex*
*area 22 superior temporal gyrus*
---
## Somatic sensory portions of the thalamus and cortical targets
<figure><img src="figs/Neuroscience5e-Fig-09.10-0_2f7fcb9.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 9.10</figcaption></figure>
Note:
Cross section view shows that there are really 4 subdivisions of primary somatosensory cortex
In VP complex, Upper body medial, Lower body lateral
---
## Receptive fields of somatosensory cortical neurons
* Area 3b and 1– cutaneous stimuli
* 3a– proprioceptive stimuli
* 2– tactile and proprioceptive stimuli
* SI is organized in columns, by receptive field, and modality. Stick an electrode vertically, all neurons share same region of body
* SI sends out projections to other areas of cortex
* SII, adjacent to SI. Receives info from all 4 SI areas and sends it to amygdala and hippocampus. Plays roles in fear conditioning and tactile learning and memory
* Submodality of the sense of touch, warns of injury and things that should be avoided
* More subjective than the other senses. The same stimulus can produce different responses in different individuals, or in the same individual in different circumstances
>20 cases have been reported in the scientific literature
>Mutations in the SCN9A gene cause congenital insensitivity to pain. The SCN9A gene provides instructions for making one part (the alpha subunit) of a sodium channel called NaV1.7.
>NaV1.7 sodium channels are found in nerve cells called nociceptors that transmit pain signals to the spinal cord and brain. The NaV1.7 channel is also found in olfactory sensory neurons, which are nerve cells in the nasal cavity that transmit smell-related signals to the brain.
>The SCN9A gene mutations that cause congenital insensitivity to pain result in the production of nonfunctional alpha subunits that cannot be incorporated into NaV1.7 channels. As a result, the channels cannot be formed.
* A family of ion channel receptors have been found that open in response to heat as well as capsaicin called TRP (transient receptor potential) channels
* Structurally resemble voltage-gated K⁺ channels, having 6 transmembrane domains that make a pore
* When open allows Ca²⁺ and Na⁺ across membrane to generate a receptor potential
Note:
---
## Heat gated ion channels
* Capsaicin receptors are nonselective cation channels opened by heat, low pH, and capsaicin (the hot in hot peppers)
* Mice without TRPV1 (VR1) have impaired sensitivity to pain. Can drink capsaicin as if it were water
<div><img src="figs/Neuroscience5e-Box-10A-1R_76f8dec.jpg" height="200px"><figcaption>Neuroscience 5e Box10A</figcaption></div>
<div><img src="figs/Neuroscience5e-Box-10A-4R_b4cd22c.jpg" height="300px"><figcaption>Neuroscience 5e Box10A</figcaption></div>
Note:
transient receptor potential cation channel subfamily V member 1 (TrpV1), also known as the capsaicin receptor or the vanilloid receptor 1 (VR1)
function of TRPV1 is detection and regulation of body temperature. In addition, TRPV1 provides a sensation of scalding heat and pain (nociception).
43ºC threshold (110ºF)
*There is recent evidence for endovanilloids that are released by other cells that can stimulate TRPV1 and contribute to nociception*
receptors for transduction of mechanical and chemical forms of nociceptive stimulation are not well understood, candidate include
- TRP family (TRPV2 and TRPA1)
- ASIC acid sensing family (ASIC3 cardiac pain)
- TRPV3 TRPV4 warm temperatures
- TRPM8 cold temperatures
*repeated applications of capsaicin desensitize pain fibers, preventing neuromodulatiors like sub P, VIP, and somatostatin from being released by PNS and CNS nerve terminals*
NAV 1.7 and NAV 1.8 are sodium channels especially important for transmission of nociceptive information
<!-- ## Nociceptors
This figure compares the activation of VR1 channels by pure capsaicin and extracts of various peppers.
<div><img src="figs/Peppers_e2e06db.png" height="100px"><figcaption>Nature 1997 Oct 23;389(6653):816-24</figcaption></div> -->
<figure><figcaption class="big">selective block of either Aδ or C fibers</figcaption><img src="figs/Neuroscience5e-Fig-10.02-0_725663b.jpg" height="300px"><figcaption>Neuroscience 5e Fig. 10.2</figcaption></figure>
Note:
---
## Hyperalgesia
* Enhanced sensitivity and response to stimulation of the area around the damaged tissue. Stimuli that would not ordinarily be perceived as pain now is. For example after a sunburn a normal shower now feels painful
* Due to the release of stuff from the damaged cells, such as prostaglandins, bradykinin, histamine, serotonin, ATP, can increase the sensitivity of nociceptors by interacting with the channel (directly or indirectly) and making it open easier, or by interacting with other receptors on nociceptive fibers to potentiate activity of TRP channels
* Aspirin and ibuprofen inhibit cyclooxygenases (COX-2 inhibitors), necessary for prostaglandin synthesis
* Shows that pain and injury are inter-related
Note:
- allodynia (hyper sensitization), clinically relevant pain from normally unpainful stimuli. Contrast with nociceptive pain (actual response to real tissue injury associated with inflammation like aches, sprains, arthritis, cancer pain, headache). Clinical issue is shifting noxious stimuli in pain sensation-stimulus intensity activation curve to the left into innocuous stimuli
- injury to a nerve is called neuropathic pain (phantom limb pain falls into this category), nerves in limbs, spinal cord, or brain can all call neuropathic pain. Also shingles, MS, spinal cord injury, cancer pain. Often severe burning sensation pain and chronic.
- phantom limb pain, often severe grip sensation (nails digging into hand)
Nice talk on pain from [Allan Basbaum UCSF](https://www.youtube.com/watch?v=gQS0tdIbJ0w). Argues against the existence of a 'pain' pathway. Can't just cut nerve to abolish pain-- maybe for acute pain but not chronic pain. peripheral sensitization.
central sensitization (pain memories)-- is a CNS disease, not a symptom of other diseases it is argued (A. Basbaum)
Sensory discriminative (SI and SII) and affective motivational (limbic system activated, including cortical areas anterior cingulate gyrus, insular cortex (between parietal and temporal lobes ventral to S1)) dimensions of the pain experience. (MC Bushnell, Basbaum lecture). **Anterior cingulate gyrus positively correlates with unpleasant experience**
More fMRI brain activation (amplitude and size of actiation) in parts of brain with same painful stimulus for females vs males. Pain threshold almost the same (45degs hot) between the sexes but is a little bit lower for women. But pain tolerance is much higher in women. (Casey et al, Basbaum lecture). Who can tolerate delivering a baby.
Expectancy can alter pain (sawamoto 2000 interesting fMRI study, after Basbaum lecture 51:07). Imaging the brain of an empathetic spouse (female) reveals activity patterns characteristic of a spouse that is in pain (no citation someone from germany, Basbaum lecture 52:27)
---
## Inflammatory response to tissue damage
<figure><img src="figs/Neuroscience5e-Fig-10.07-0_acb1914.jpg" height="500px"><figcaption>Neuroscience 5e Fig. 10.7</figcaption></figure>
Note:
Another type of peripheral sensitization can occur due to substances released within damaged tissues can modulate the response of nociceptive fibers. A host of molecules that can augment the activity of free nerve endings like…
Most interact directly with the receptors or ion channels of the nociceptive fibers. e.g. TRPV1 capacin receptor can be potentiated form the channels direct interactions with extracellular protons that are released by immune cells or through indirect interaction with other enzyme receptors like TrkA for NGF or bradykinin receptors.
**Prostaglandins reduce the threshold depolarization needed for AP generation by phosphorylation of special TTX resistant Na+ channels expressed in nociceptor afferents and also incr levels of cAMP.**
Cells that contribute to this inflammatory soup include mast cells, patelets, basophils, macrophages, neutrophils, endothelial cells, keratinocytes, and fibroblasts. Cells are responsible for releasing protons (lowering the pH), arachidonic acid, bradykinini, histamine, serotonini, prostaglandins, neucleotides, NGF, cytkines (interleukin 1beta, and TNF-alpha). COX2 inhibitors, NSAIDs -- or nonsteroidal anti-inflammatory drugs block Cox-1 and Cox-2 enzymes so that prostaglandins can't be made.
>a peptide that causes blood vessels to dilate (enlarge), and therefore causes blood pressure to fall
nociceptive
: of or related to pain arising from stimulation of nerve fibers
---
## Pain pathways
* Spinothalamic tract
* Cell bodies found in the most lateral parts of the dorsal root ganglia, but not discretely localized.
* Innervate neurons in the dorsal horn of the spinal cord. Some of these neurons project within the spinal cord. These are important for reflex behaviors.
* Others project axons cross the midline in the same segment and then go up to the brain.
Note:
---
## Major pathways for pain (and temperature) sensation of the body
nociceptive projections into dorsal horn branch into ascending and descending collaterals forming the dorsolateral tract of Lissauer (named after 19th c. German neurologist).
C fibers (slow pain) terminate in layer 1 (Rexed’s laminae, named after anatomist who first described spinal gray matter layers in 1950s) of dorsal horn.
Adelta (fast pain) terminate in layer 5 of dorsal horn where Abeta mechanosensory terminals innervate.
---
## Pathways for pain (and temperature) sensation of the face
<figure><img src="figs/Neuroscience5e-Fig-10.06-2R_b1ab19b.jpg" height="500px"><figcaption>Neuroscience 5e Fig. 10.6</figcaption></figure>
* Pain and temp go to VPM and VPL nuclei just like the mechanosensory axons
* VPM from the face, VPL from the body
* Presumably responsible for our ability to locate a pain with respect to body position
<figure><figcaption class="big">upper body medial, lower body lateral</figcaption><img src="figs/Physiology-6e-nociception-thalamus_copy_496c648.jpg" height="200px"><figcaption>Berne and Levy, Physiology 6e Elsevier</figcaption></figure>
* VPM and VPL neurons project to primary somatosensory cortex. These thalamic neurons have small receptive fields and are likely used to locate where the pain is, but are not responsible for dull aches that are associated with chronic pain as ablation does not reduce pain
* There are also direct projections to the reticular formation (in medulla), and the midline thalamic nuclei. These neurons project to areas of the limbic system and are responsible for the emotional aspects of pain
Note:
---
## Anterolateral system sends information to different parts of the brainstem/forebrain
<figure><img src="figs/Neuroscience5e-Fig-10.05-0_15cc148.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 10.5</figcaption></figure>
Note:
sensory discrimative: location, intensity, and quality of noxious stimulation
affective-motivational: unpleasant feeling, fear, anxiety, autonomic activation for fight-flight
---
## Spinothalamic tract
<div style="font-size:0.8em;width:500px">
<div></div>
* Also called anterolateral column part of the ventral column
* Note where axons cross over the midline
* Touch and pain are on opposite sides below medulla
* Touch and pain are on the same side above medulla
</div>
<div><img src="figs/Neuroscience3e-spinothalamic_copy_90b491e.jpg" height="400px"><figcaption>Neuroscience 2e 2001</figcaption></div>
Note:
---
## The anterolateral and dorsal column-medial leminiscal systems cross the midline at different sites
<figure><img src="figs/Neuroscience5e-Fig-10.04-0_1f88ca5.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 10.4</figcaption></figure>
Note:
nociceptive and mechanosensory pathways
--
## Pain vs touch
* 2nd order mechanosensory axons cross at the level of the medulla but 2nd order pain axons cross at about the segment their cell bodies are in
* If there is a damage on one side of the spinal cord, below the injury site, there would be no sense of touch on the same side and no sense of pain on the contralateral side
---
## Referred pain
<div style="font-size:0.8em;width:500px">
<div></div>
* Few if any neurons in dorsal horn are specialized solely for the transmission of visceral pain
* It is conveyed to brain via dorsal horn neurons that also get inputs from skin
* Therefore a person may feel pain at a site completely different than its source
anginal pain which is pain arising from heart muscle that is not being adequately perfused with blood. Referred to the upper chest wall, with radiation into the left arm and hand.
Innervation of same neuron in the dorsal horn of the spinal cord.
* There is a descending pain pathway that can impinge on the dorsal horn to quiet neurons
Note:
---
## Brain modulation of ascending pain signals
* Stimulation of periaqueductal grey (in midbrain) or rostral medulla reduces pain, producing analgesia
* Stimulation only reduces pain sensation, animal/person still responds to touch, temp etc, just feels less pain
* Cerebral cortex and hypothalamus project to periaqueductal gray which then projects to nuclei in the medulla (Raphe nuclei, reticular formation), which project to the dorsal horn and inhibit ascending pain fibers, forming a descending pathway that modulates pain
Note:
--
## Modulation of ascending pain signal transmission
<div><img src="figs/Neuroscience5e-Fig-10.08-1R_09cfa4c.jpg" height="300px"><figcaption>Neuroscience 5e Fig. 10.8</figcaption></div>
Note:
enkephalins, endorphins, dynorphins— present in the periacq. gray matter, ventral medulla, and in spinal cord regions in dorsal horn.
Also CB1 and endocannabinoids work similiarly here in the dorsal horn. CB1 on presynaptic terminals of dorsal horn nociceptive terminals can be activated by endocannabinoid release in a retrograde fashion and decrease the release of neurotransmitters such as GABA and glutamate. *Interestingly, the analgesic effecs of PAG stimulation is blocked if CB1 antagonists are administered* highlighting the importance of endocannabinoids in descending control of pain transmission.
## Modulation of ascending pain signal transmission
* Axons from neurons with mechanoreceptors can synapse onto inhibitory interneurons in spine to dampen pain response
* Descending pathways from the brainstem can dampen pain response
<div><img src="figs/Neuroscience5e-Fig-10.08-2R_copy_a581560.jpg" height="300px"><figcaption>Neuroscience 5e Fig. 10.8</figcaption></div>
<div><img src="figs/Neuroscience5e-Fig-10.08-3R_9baa76a.jpg" height="300px"><figcaption>Neuroscience 5e Fig. 10.8</figcaption></div>
Note:
enkephalins, endorphins, dynorphins— present in the periacquaductal gray matter, ventral medulla, and in spinal cord regions in dorsal horn.
Also CB1 and endocannabinoids work similiarly here in the dorsal horn.
--
## Descending systems modulate the transmission of ascending pain signals
<figure><figcaption class="big">Descending pathways from cortex and hypothalamus</figcaption><img src="figs/Neuroscience-3e-descendingpainmodulation1_copy_99372b9.jpg" height="400px"><figcaption>Neuroscience 2e 2001</figcaption></figure>
Note:
--
## Descending systems modulate the transmission of ascending pain signals
<figure><figcaption class="big">Descending output from periaqueductal gray–rostral medulla reduces activity in spinothalamic tract</figcaption><img src="figs/Neuroscience-3e-descendingpainmodulation2_copy_beb8ab0.jpg" height="400px"><figcaption>Neuroscience 2e 2001</figcaption></figure>
Note:
--
## Endogenous opioids dampen pain signal transmission
* Opioid receptors (metabotropic) are expressed in the areas of descending pain pathway (also expressed in other areas, such as muscles of the bowel and anal sphincter)
* Ligands– enkephalins, endorphins, and dynorphin. Found in all descending pain areas
* Opioids decrease the chance that a nociceptor afferent will fire by causing inhibition
* Opiate antagonist naloxone (competitive opioid receptor antagonist) blocks stimulation produced analgesia as well as morphine-induced analgesia. Suggests that they are the same thing
Note:
endogenous opioids
: all are 5–30 a.a. long peptides
: enkephalins, endorphins, dynorphins
* leucine-enkephalin
* methionine-enkephalin
* alpha-endorphin
* alpha-neoendorphin
* beta-endorphin
* gamma-endorphin
* dynorphin A
* dynorphin B
- oxycontin, percoset
---
## Placebo effect
* Sugar pills can reduce perception of pain
* Effect can be blocked by naloxone, a competitive antagonist of opioid receptors
* Therefore placebo effect is based on a biochemical change in the brain, as are all perceptions
Note:
- mind separate from body. No– this highlights something that neuroscientists already widely accept, that you cannot separate the mind from the body, the mind is body and vice versa
- what is or is not reality philosophers
- highlights descending control and higher order processing of pain
- children are not placebo reactors less than 10 yr old. acupuncture works likely as a placebo (needle can be stuck anywhere). Hypnosis can alter perception (reduce activity in anterior cingulate) without sensory discrimination (Rainville Science 1997). But not sensitive to naloxone, so not through opiate system.
Phantom limbs can be another fascinating clue to higher order processing of somatic sensation. This stems from the fact that for amputees, almost all have an illusion that the missing limb is present.
It’s been proposed that there is an internal mismatch between the brain’s representation of the body and the pattern of peripheral tactile input that results in the illusory sensation.
