sensory processing

Sensory processing: touch and pain


Outline: touch and pain

   Recap

  • Receptors + fibers

  • Primary afferents

  • Touch

    • Skin receptors

    • Sensory pathways

    • Organization

  • Pain

    • Dimensions

    • Pathways 

    • Control


Coding sensory input

  • Sensory neurons code information by

    • Location of stimulus

    • Modality (perceived type of stimulus)

    • Intensity (frequency coding, population coding)

    • Duration (number, frequency


Skin - variety of receptors for touch

  • Superficial layers

    • Merkel disks: fine texture, pressure

      • Fine texture, pressure, position, slowly adapting,respond to isolated points and edges

      • Fire only when in contact with stimulus, adapt slowly, so they fire continually - represent form

    • Meissner's corpuscle - fine mechanical sensitivity, stroke

      • Fine mechanical sensitivity, stroke, shape and textural changes - rapidly adapting/phasic

      • Larger receptive fields - do not distinguish between letters - adapt quickly, aka with sustained stimulation, the response decreases rapidly before ceasing

    • Deformation allows for Na+ ions to enter = action potential

  • Deep subcutaneous tissue: 

    • Pacinian copuscle: vibrations; sensitive to textures, rapidly adapting

      • Respond to vibration - provide info about texture

    • Ruffini’s ending: detect stretching of skin when we move fingers or limbs, slowly adapting

      • Fire while skin is stretched over stimulus, but don’t completely represent form - adapt slowly


 Tonic receptors respond for the duration of a stimulus

Phasic receptors adapt to a constant stimulus


Thermal receptors: free nerve endings

  • Cool receptors: cool

  • Warm receptors: warm

  • Heat nociceptors: painful hot

  • Cold nociceptors painful cold

  • Free nerve endings

  • ThermoTRP

    • Temperature sensitive ion channels in the transient receptor potential 

    • Capsaicin, menthol

    • Identify stimuli and regulate temperature

    • Receptive fields: more cold than warm spots


Primary afferent fibers

  • Receptor structure/nerve ending

  • Fiber - myelinated or unmyelinated

  • Myelinated

    • AB fibers - mechanical, temperature (non-pain)

    • Ad fibers - nociceptor, temperature - sharp pain

  • unmyelinated(slow)

    • C fibers - nociceptor, temperature - dull pain, burning pain or itch


Touch and pain sensory pathways

  • Two pathways carry sensory info from skin to brain:

    • Touch pathway: dorsal column/medial lemniscus

    • Pain pathway: spinothalamic tract

  1. Ab primary afferent: myelinated mechanoreceptor

    1. First order neuron

  2. Dorsal root ganglia

  3. Synapses on second order neuron in brainstem

  4. Decussates

  5. Goes to thalamus

  6. Synapses on third order neuron

  7. Goes to primary somatosensory cortex


Dermatome

  • Strip of skin innervated by a particular spinal root

    • Cervical

      • Head, neck, arms

    • Thoracic

      • trunk

    • Lumbar

      • Front of legs

    • Sacral

      • Back of legs


Somatotopic cortical organization

  • Brain cells are arranged according to body map


Pain and nociception

  • Pain: an unpleasant sensory and emotional experience associated with, or, resembling that associated with, actual or potential tissue damage

    • Adaptive purpose - helps us to: 

      • Withdraw from its source

      • Engage in recuperative actions

      • Signal others

  • Nociception: neural mechanism involved in detecting tissue damage

    • Peripheral receptors on free nerve endings that respond to painful stimuli

    • When tissue is injured, affected cells release chemicals that can activate nociceptors

      • Serotonin, histamine, various enzymes and peptides

  • Pain and nociception are different phenomena. Pain cannot be inferred solely from activity in sensory neurons


Touch and pain sensory pathway

  • Two pathways carry sensory info from skin to brain


Pain pathways

  • Injured cells release substances that:

    • Cause local inflammation

    • Stimulate primary afferent nerve endings

    • Ad and C fibers carry information to the dorsal horn of the spinal cord

  • Synapse on spinal neurons that project across midline, before ascending to the thalamus

  • Pain information is integrated in the cingulate cortex

    • Extent of activation in cingulate correlates with how much discomfort different people report in response to same mildly painful stimulus

      • Empathy


Neuropathic pain

  • Neuropathic pain

    • Due to inappropriate signaling of pain by neurons

      • Nerve damage rather than “tissue damage”

    • Phantom limb pain

      • Continued perception of chronic pain despite missing limb

      • Some improvements using a mirror to trick the brain into believing it is controlling the missing limb

        • Visual feedback


Pain control: sensitization

  • Hyperalgesia - increased pain to stimuli that normally do not evoke pain

  • Sensitization: enhanced pain responsiveness to nociceptive stimulus

    • Primary afferent sensitization 

      • Explains primary hyperalgesia

    • Central sensitization

      • Explain secondary hyperalgesia

        • Undamaged skin nearby is hypersensitive

      • Dorsal horn or thalamus/cortex


Pain is a biopsychosocial phenomenon


Endogenous pain control

  Endogenous pain modulatory systems can either inhibit or enhance the pain based upon context or expectation

  • Placebo analgesia: with expectation of morphine analgesia

    • Tourniquet on arm for 5 days while squeezing exercise ball (unbearable after about 13 min)

  • Nocebo 



Endocrinology

Outline:

  1. Defining hormones: secretion

  2. Transport and target reach

  3. Potency

  4. Specificity of action


Types of chemical communication

  • Endocrine: enter the blood stream

    • Secretion into the bloodstream to affect distant target tissue physiology and function

  • Neural: synaptic transmission

    • Neurons release NT into synaptic cleft to influence target neuron

  • Pheromone

    • Chemical signal to conspecifics

  • Allomone

    • Chemical signal to other species

  • Exocrine

    • Gland (e.g. sweat) releases enzymes, fluids via ducts to outside of body

  • Paracrine

    • Cells release factors that diffuse over short distances to affect other cells

  • Autocrine

    • Cells release factors that bind to receptors on same cell to elicit effect

  • Endocrine

    • Endocrine cells send signals across distance


Endocrine vs signaling

  • Similarities

    • Both produce and store signaling factors (hormones or NTs) for later release

    • Both stimulate or inhibit targets with chemicals/signaling factors

    • Large repertoire of signaling factors (i.e. many hormones, many NTs)

    • Can activate 2nd messenger pathways in target cells

  • Differences: 

Endocrine

Neural (synaptic)

Local or widespread, but diffuse

Release NTs to precise destination

Relatively slow (typically minutes)

Very fast (milliseconds - seconds)

Always graded

All or none APs +graded synaptic potentials

Feedback homeostatic control

Often feedback, but not necessarily homeostatic in nature


Endocrinology

  Hormones

  • Hormones are secreted by a cell or group of cells

  • Hormones are secreted into the blood and circulate 

    • Except pheromones

  • Hormones are transported to distant targets

    • Except one region's hormones can be another’s signaling molecule

    • E.g. oxytocin is a neurotransmitter in the brain, but when released into the blood, it acts as a hormone

  • Act at very low concentration - 1 x 10^-12

  • Specificity comes from where the receptors are located!

    • Pathological when receptors are expressed in inappropriate places - like tumors


Terminology

  • Hormones

  • Chemicals released by an endocrine gland into the bloodstream that regulate specific target organs/tissues/cells

  • Target produce physiological response

  • Endocrine glands

    • Release hormones into bloodstream to act on distant target tissue physiology and function

  • Homeostasis

    • Maintenance of a constant interval state or environment


Berthold’s key experiment

  • Removal of testes from young roosters

    • Transplanted back into abdomen immediately

    • No neural innervation

    • Huge effects on body and behavior

    • Testes must release chemical into blood that acts broadly


Endocrine organs in males and females

  • Gonads: body development; maintenance of reproductive organs in adults

  • Hypothalamus: control of hormone secretion

  • Pineal gland: reproductive maturation; body rhythms

  • Pituitary gland

    • Anterior pituitary: hormone secretion by thyroid; adrenal cortex; gonad, growth

    • Posterior pituitary: water balance, salt balance

  • Thyroid: growth and development; metabolic rate

  • Adrenal glands

    • Adrenal cortex: salt and carbohydrate metabolism; inflammatory reactions

    • Adrenal medulla: emotional arousal

  • Pancreas: sugar metabolism

  • Gut: digestion and appetite


Structural classes of hormones

  • Peptide hormones: made in advance in the cell, where it is stored in a vesicle

    • Strings of amino acids

    • E.g. ACTH

    • Released into the plasma, dissolve

    • Most bind receptors on target cell’s membrane (usually a GPCR)

    • When the extracellular site is bound, shape of the receptor changes, initiating 2nd messenger

    • Specificity is determined by presence and availability of the receptor on the cell

    • Relatively rapid (seconds to minutes) effects

    • The precursor, the pre-hormones, gets cleaved

    • But when it gets cleaved, it does not make multiple copies of the same hormone; it actually makes three different hormones

    • ACTH - triggers the release of cortisol, a stress hormone

    • Lioptropin tells adipose cells to metabolize fat

    • Beta endorphin binds to Mu opioid receptors and other opioid receptors to inhibit pain

  • Amine hormones: most bind receptors on target cell’s membrane

    • Modified single amino acids

    • E.g. melatonin, thyroxine, epinephrine

    • Long acting and short acting types (some act like peptides and some act like steroids)

    • Catecholamines - from tyrosine -act like peptides - short acting

      • norepinephrine , epinephrine

    • Thyroid hormones - act like steroids, intracellular receptors, long acting

    • Specificity is determined by presence and availability of the receptor on the cell

  • Steroid hormones: made on demand, cant be stored because they are lipophilic

    • Derived from cholesterol - 4 rings of carbon atoms

    • Lipophilic and membrane permeable

    • E.g. estradiol, cortisol

    • Diffuse out of the cell and bind to carrier proteins in the plasma

    • They pass through the membrane of cells

    • Bind receptors inside the cell (cytosol) and transported to nucleus

    • Bind specific DNA sequences to modulate gene expression

    • Alters protein production for fast (hours to days), but long-lasting effects


Hormone interaction: 

  • Synergistic: combine for stronger effect

  • Permissive: allowing for another effect

  • Antagonistic: hormone can block effect of another


Main sources of hormones in the brain

  • Pituitary

    • Pea-sized gland at base of skull in midline

    • 2 anatomically and functionally discrete divisions: anterior and posterior

  • Hypothalamus

    • Sits above the pituitary and under the thalamus

    • Connects to anterior pituitary via stalk (infundibular or pituitary stalk)


Posterior pituitary system

  • Posterior pituitary develops as an extension of hypothalamus

  • Releases hormones, but hormones not made in posterior pituitary

  • Neuroendocrine cells in two hypothalamic regions (PVN, SON) project axons down the infundibulum

  • Axon terminals in posteriori pituitary release 2 hormones into capillary bed

    • Oxytocin

      • Peptide hormone (9 amino acids)

      • Stimulates uterine contractions

      • Triggers milk letdown reflex

      • Mediates sexual arousal and affectionate responses

    • Vasopressin(antidiuretic hormone)

      • Peptide hormone (9 amino acids)

      • Structurally similar to oxytocin

      • Increases blood pressure

      • Conserves water (antidiuretic)

      • “Monogamy” hormone in prairie voles


Anterior pituitary system: releasing hormones

  • Hypothalamic neuroendocrine cells produce releasing hormones

  • Releasing hormones secreted into “hypothalamus - pituitary portal system” or capillaries

  • Hormones travel to anterior pituitary and locally affect hormone-producing cells in the anterior-pituitary

  • Anterior pituitary cells then release many tropic hormones into the bloodstream

    • Directed “toward”

    • Tropic hormones stimulate endocrine glands (e.g. thyroid and ovaries)

Tropic hormones

  • ACTH - adrenocorticotropic hormone

    • Peptide

    • Effector organ: adrenal cortex

    • Stimulates secretion of glucocorticoids like cortisol

  • TSH - thyroid stimulating hormones

    • Glycoprotein (2 subunits)

    • Effector organ: thyroid

    • Stimulates secretion of thyroxine and triiodothyronine

  • FSH - follicle stimulating hormone

    • Glycoprotein

    • Effector organ: ovaries or testes

    • Stimulates growth of gonads, oestrogen secretion and spermatogenesis

  • LH - luteinizing hormones

    • Glycoprotein

    • Effector organ: ovaries, testes

    • Stimulates sex hormone production

  • GH - growth hormone

    • Peptide

    • Effector organ: All tissues

    • Stimulates growth and metabolism


Negative feedback regulation

  • An essential homeostatic mechanism controlling hormone release

  • Posterior pituitary system: biological response is detected by the brain, which halts further hormone release

  • Anterior pituitary system: hormones from the endocrine gland have a negative feedback on both the hypothalamus and pituitary


Endocrine organ affected by anterior pituitary hormones

  • Adrenal gland

    • Adrenocorticotropic Hormone (ACTH) - controls production and release of adrenal cortex hormones (which control release of steroid hormones)

  • Thyroid

    • Thyroid stimulating Hormone (TSH) - controls release of thyroid hormones

  • Gonads

    • FSH - follicle stimulating hormone - stimulates growth of gonads, oestrogen secretion and spermatogenesis

    • LH - stimulates sex hormone production


HPA - adrenal gland

  Hypothalamic pituitary adrenal 

  Two parts:

  1. Adrenal cortex : outer bark of the adrenal gland; releases adrenocorticoids

    1. 3 classes, glucocorticoids (e.g. cortisol), mineralocorticoids (e.g. aldosterone), sex steroids (e.g. androstenedione)

  2. Adrenal medulla : inner part

    1. Releases epinephrine and norepinephrine in response to sympathetic nervous system activation


Anterior pituitary Hormone Pathway: cortisol

  • HPA Axis

  • Cortisol

    • Glucocorticoid

    • Stress hormone induced by psychological stress, hypoglycemia, infection

    • Increases glucose production

    • Suppresses immune system

  • Hypothalamus → corticotropin releasing hormone (CRH) → anterior pituitary → adrenocorticotropic hormone (ACTH) → adrenal cortex → cortisol → stress response

  • Too low cortisol

    • Low ACTH

    • Addison’s disease, autoimmunity, hypotension

    • Take synthetic steroids

  • Too much cortisol

    • High ACTH

    • Cushing’s syndrome, chronic stress, hypertension, impaired memory formation

    • Drugs, surgery


Loss of homeostasis leads to disease

  1. Over or under production of H1, H2, or H3 can be pathological

  2. Dysregulation of receptor signaling

  3. Down-regulation of the receptor

  4. hypo/hyper secretion (too little or too much)

  • Primary pathology: failure of “final” hormone

  • Secondary pathology: failure of “tropin” hormone


Cushing's syndrome

  • Primary pathology

    • Pathology in the adrenal cortex - they make too much cortisol

    • High cort, suppressing ACTH and CRH = low ACTH and CRH

  • Secondary pathology

    • Tumor in the anterior pituitary → too much ACTH

    • ACTH increases CORT production

    • Low CRH

  • Look where in the pathways are high and low to determine whether it is a secondary or primary pathology


Addison's disease

  • Primary pathology

    • Pathology in the adrenal cortex - not enough CORT

    • Low CORT, does not suppress ACTH and CRH = high ACTH and CRH

    • Failure in feedback loop