JD

Sensory Systems: Pain & Chemosensation

Sensory Receptors

  • Sensory systems encompass pain and chemosensation.
  • The pathway involves sensory neurons, interneurons, motor neurons, and the spinal cord.

Adaptation

  • Adaptation is the process where sensory receptors reduce responsiveness to constant stimulation.
  • DRG (Dorsal Root Ganglion) cells respond to both spatial and temporal properties of stimuli.
  • Slowly adapting receptors continue responding to a stimulus.
  • Rapidly adapting receptors respond only at the onset (and sometimes offset) of stimulation, signaling static and dynamic qualities.

Temperature & Pain

  • Thermoreception involves sensing cool and warm stimuli.
  • There are two categories of free nerve-ending thermal receptors: those responding to warmth and those to coolness.
  • Warmth and coolness are relative.
  • TRP receptors, such as TRPM8, respond to menthol.
  • Nociception (pain) involves three types of pain receptors.
  • High-threshold mechanoreceptors respond to intense pressure (striking, pinching).
  • Receptors also respond to extremes of heat, acids, and capsaicin (binds to TRPV1 receptor).
  • Pungent irritants (horseradish, garlic, tear gas) bind to TRPA1.

Somatosensory Pathways

  • Fine touch, proprioception, and vibration ascend through the dorsal column pathway.
  • Nociception, temperature, and coarse touch ascend through the spinothalamic pathway.
  • Pain, temperature, and coarse touch cross the midline in the spinal cord.
  • The pathway includes primary, secondary, and tertiary sensory neurons.

Somatosensory Pathways Details

  • The dorsal column pathway includes the dorsal column nuclei in the medulla oblongata and decussates at the medial lemniscus.
  • The spinothalamic pathway includes the Lissauer's tract and the anterolateral quadrant.
  • Both pathways project to the thalamus and then to the primary somatosensory cortex.

Primary Sensory Cortices

  • The primary sensory cortices include the insular cortex, primary auditory cortex, and primary visual cortex.
  • The primary somatosensory cortex is located in the parietal lobe, posterior to the central sulcus.
  • Feet, trunk, hands, fingers, face, and lips are represented along the somatosensory cortex.

Functional Organization

  • The somatosensory cortex is organized topographically.
  • Cortical columns are present, with neurons responding to a particular type of stimulus applied to a specific body part.

Cortical Reorganization

  • Cortical reorganization or functional remapping occurs in the somatosensory cortex following amputation.
  • For example, after digit 3 amputation, the area that formerly responded to digit 3 now responds to stimulation of digits 2 and 4.
  • Example given: (M. M. Merzenich et al., 1984. J Comp Neurol 224: 591–605.)

Tactile Agnosias

  • Damage to the somatosensory association cortex results in tactile agnosias: an inability to recognize or identify tactile stimuli.
  • Patients may be unable to recognize objects by touch or draw them based on touch alone.

Pain

  • Pain is primarily a warning sign, signaling tissue damage or potential damage at the nociceptor level.
  • It elicits a withdrawal reflex or verbal report.
  • Inflammation or increased sensitivity discourages further activity.
  • Perception of pain is tactile, emotional, and modifiable.

Three Components of Pain

  • Pain has three perceptual and behavioral components:
    • Sensory component (somatosensory pathway).
    • Immediate emotional component (anterior cingulate cortex (ACC) and insular cortex).
    • Long-term emotional component (prefrontal cortex).

Methods of Pain Modification

  • Pain can be modified by:
    • Opioids.
    • Administration of placebos.
    • Hypnosis.
    • Other forms of stimulation, such as acupuncture.

Midbrain Role in Pain Relief

  • Endogenous opioids are neuropeptides with widespread effects.
  • Exogenous opioids/opiates can bind to the same receptors.
  • Opioids can bind to the periaqueductal gray (PAG) and initiate pain modulation/analgesia.

Opioid-Induced Analgesic

  • Without opioids, PAG neurons are inhibited, interneurons are not activated, and there is no inhibition of pain signals.
  • With opioids, inhibition of PAG is blocked (disinhibition), interneurons are activated, and pain signals are inhibited.
  • In the spinal cord, pain signals to the brain can be modified by inhibitory interneurons.

Brain Regions Involved in Response to Pain-Relieving Placebo

  • PET imaging demonstrates endogenous opioids binding to μ-opioid receptors following placebo administration in several brain regions.
  • Source: Based on: Zubieta et al., 2005

Phantom Limb Pain

  • After limb amputation, individuals often feel pain in their missing limb.
  • Three hypotheses:
    • Peripheral Nerve Activity: Sensory axon still active despite being cut (forming a neuroma).
    • However, cutting above the neuroma doesn’t always relieve pain.
    • Cortical Reorganization: Sensation in missing limb is produced by reorganization of the missing limb’s area of somatosensory cortex.
    • Internal Representation: Conflict between visual feedback and proprioceptive feedback.
    • Distress occurs when no visual movement corresponds with internal representation/intention of movement.

Mirror Box Therapy

  • Mirror box therapy is designed to relieve phantom pain, particularly with upper limb loss, by providing visual feedback that corresponds to intended movements.

Olfaction (Smell)

  • Similar molecules can generate distinct olfactory sensations.
  • Odors (odorants) are volatile substances.
  • Olfaction helps identify food and avoid spoiled food.
  • The olfactory system is second only to the visual system in the number of sensory receptor cells.
  • Humans can recognize up to 10,000 odorants.

Olfaction Process

  1. Odorants bind to receptors.
  2. Olfactory receptor cells are activated and send electrical signals.
  3. Signals are relayed via converged axons.
  4. Signals are transmitted to higher brain regions.

Olfactory Receptor Cells and Glomeruli

  • Olfactory receptor cells of different types contain different receptor molecules.
  • Receptors are metabotropic (GPCRs).
  • Each glomerulus of the olfactory bulb receives information from only one type of receptor cell.
  • Olfactory receptor cells release glutamate onto mitral cells.

Olfactory Information Encoding

  • Humans have 339 different olfactory receptor genes (mice have 913) and 2,000 glomeruli.
  • Odorants bind to many receptors (not 1:1).
  • The location of glomeruli appears the same across individual rodents.
  • Smell is encoded in the pattern of glomerulus activity.

Olfactory Pathway

  • The olfactory pathway includes the olfactory bulb, pyriform cortex (primary olfactory cortex), amygdala, thalamus (medial dorsal nucleus), and orbitofrontal cortex (secondary olfactory cortex).
  • Olfactory information is conveyed to emotional centers (limbic system).

Olfactory Nerves and Emotional Areas

  • Olfactory nerves also send information to emotional areas, including the hypothalamus, amygdala, and hippocampus.

Gustation (Taste)

  • Five qualities of taste: bitterness, sourness, sweetness, saltiness, and umami.

The Tongue

  • Papillae (single: papilla) are small protuberances of the tongue.
  • Taste buds: groups of 20-50 taste cells.
  • Microvilli of each taste cell project through a taste pore.

Taste Buds

  • Taste pore allows saliva to contact taste cells.
  • Taste cells have a lifespan of 10-14 days and are supported by basal cells.
  • Gustatory afferent nerves transmit taste information to sensory ganglia.

Taste Maps

  • Taste maps are a myth; instead, the density of taste buds differs between locations of the tongue.
  • Each taste bud has receptors for all tastes.

Taste Cell Modalities

  • Different taste cells are dedicated to different taste modalities.
  • Taste ligands create Ca^{2+} signals that release serotonin or ATP.
  • Receptor cells exist for sweet, umami, bitter, salty/sour, and CO_2.

Taste Receptors

  • Different types of tastants are detected by different taste cells that express distinct metabotropic or ionotropic receptors.
    • Sour: H^+ sensitive channel
    • Sweet: T1R2 + T1R3
    • Umami: T1R1 + T1R3
    • Bitter: T2Rs
    • Salty: Na channel

Gustatory Chemotransduction

  • Carbonic anhydrase-4 (Car4) involved in CO_2 detection

Gustatory Pathway

  • The gustatory pathway includes:
    • Nucleus of the solitary tract (medulla)
    • Thalamus
    • Primary gustatory cortex (insular cortex)
    • Secondary gustatory cortex (orbitofrontal cortex).
  • Taste is ipsilaterally represented in the brain.
  • fMRI evidence suggests that different tastes activate different parts of the insular cortex, but locations differ between people.
  • Taste information is also conveyed to emotional centers.

Flavor

  • Flavor derives from a combination of sensory inputs: taste, olfactory, and somatosensory.