LO: Define the types and properties of sensory receptors and key neurotransmitters involved in sensory and motor pathways

Temperature sensing

• Thermoreceptors
• TRP channels: temperature change, channel opens, sodium/calcium influx leads to action potential

Receptors in CNS

• Predominantly warm sensitive
• TPRM2 in preoptic anterior hypothalamus
• Guard closely against overheating

Receptors in periphery

• Predominantly cold sensitive
• TPRM8 in skin
• Phasic - respond to changing temperature
• Sensitive to change: 0.003$\mathrm{°}$C detection
• Variability in distribution

Temperature pathway

• Spinothalamic tract (three neuron chain)
• Cold signal - A$\delta$ fibers (fast)
• Warm signal - C fibers (slow)
• Synapse at point of entry, immediate decussation
• Conscious information heads to the somatosensory cortex
• Subconscious to hypothal

LO: Define homeostasis and describe the homeostatic control of temperature

Thermoeffector

• Hypothal coordinates appropriate effector responses
• Two neuron chain
• Preventative effectors: behaviour, vasomotor
• Corrective effectors: thermogenesis, sweating

Altered regulation

• Non-thermal factors in temperature control-modulation
• Altered onset thresholds or magnitude of response

Pyrexia/anapyrexia

• Actively defended (regulated) hypothalamic mediated shifts in body temperature
• Evolutionary protective underpinnings
• Pyrexia - fever (regulated hyperthermia - increased temperature)
  • Adaptive defence to enhance immune system ability to fight infection
  • Create hostile environment for pathogens
• Anapyrexia - regulated hypothermia (decreased temperature)
  • Survival mechanism - links to hibernation
  • Reducing metabolism and O₂ consumption
  • Provides neuroprotection

Anapyrexia

• Inverse of pyrexia
• Links between O₂ availability, temperature and metabolic rate
• Several signalling molecules and NTs involved
• Nitric oxide - thought to be key

LO: Describe the pathophysiology of fever

Pyrexia

Initiation

• IL-6-COX2-PGE2 axis
• Exogenous pyrogens enter body
• Exogenous pyro - bacteria, virus, toxin
• Endogenous pyro - pyrogenic cytokines resulting from immune response to exogenous pyro
• Pyro - act on hypothalamic endothelium leading to cyclooxygenase-2 (COX2) expression

Mechanism

• COX2 converts arachidonic acid into prostaglandin
• PGE2 alters hypothal set points
• PGE2 inhibits warm sensitive neurons which would inhibit cold responses via GABA

Net response

• Altered set points creates error signal between sensed and target temperature
• Error signal - resolved by activation of heat preservation and heat production thermoeffectors
• Vasoconstriction, BAT activation, shivering
• Cross inhibition of sweating
• Afferent modulation - PGE2 inhibits warm and stimulates cold sensitive neuro-afferent signals
• PGE2 action in lateral parabrachial nucleus (LPB) in brainstem and central amygdala (CeA)
• Results in cold 'thermal sensation' warm seeking behaviour
• Fever 'breaks': PGE2 reduces, system resets
• Initiate strong sweat response to rapidly cool body