LO: Discuss the pathophysiology of pain

Transduction - conversion of noxious stimuli into a neural signal
Transmission - ascending relay of signal from periphery to CNS
Perception - conscious sensory experience
Modulation - alteration of the ascending signal

Transduction

• Polymodal receptors - chemical, thermal, mechanical
• Free nerve endings in dermis of skin
• Transmembrane protein that transduces stimulus to signal
• Receptors/molecular sensor

Transmission

• Fibre types: A$\delta$ (sharp, localised) and C (dull)
• Spinothalamic tract - sensation
• Spinoreticular tract - slower 'limbic system'
• Synapse at point of entry, immediate decussation (nerve crossover)

Perception

• Pain connectome - interlinking concurrent processing
• Somatosensory cortex - where
• Homunculus
• Limbic system - emotion/fear/stress
• Reticular formation - awake
• Response - behaviour and motor response

Modulation

Peripheral

• Nociceptor activation threshold is dynamic (go up or down)
• Driven by sensitising soup and key sub-mediators
  Sensitising soup: Bradykinin, Prostagalndin E2 (PGE2), Nerve growth factor

Central

• Descending synaptic modulation
• Ascending nociceptive signal is in balance of excitatory and inhibitory control by interneurons
• Descending periaqueductal gray (PAG) are inhibitory, but are inhibited via GABA
• GABA inhibition is released when PAG is activated by ascending pain signals - takes off brakes

LO: Describe the anatomical pathways along which pain is transmitted and the physiological mechanism

Central modulation

• Target - ascending dorsal horn 1^st and 2^nd order synapse in spine
• Activated receptors in PAG activate descending serotonergic and noradrenergic neurons
• Hyperpolarisation of pre and post synaptic terminals dampen transmission (refractory period)

LO: Discuss the fundamentals of the endogenous pain relieving mechanisms

Exogenous hacking

• Endogenous pathways can be hacked
• PAG rich in opioid receptors
• Exogenous opiates mimic endogenous opioids
• Opiates acts on the PAG to trick brain into sending serotonergic and noradrenergic signals
• Paracetamol - tricks brain to sending serotonin down spinal cord to block afferetn pain signals