pain pathways

define pain

unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage

what is nociception

mechanism by which noxious peripheral stimuli are transmitted to CNS

how does nociception differ from pain

nociception is signal whilst pain is perception and emotional interpretation

what is a noxious receptor (aka nociceptor)

nerve ending that detects damaging stimuli

name the different types of pain

• nociceptive/acute pain

• chronic 

• neuropathic

  • central neuropathic pain

  • peripheral neuropathic pain

what is nociceptive/acute pain

pain from soft tissue damage, infection or inflammation with identifiable cause and location

what is chronic pain

pain lasting more than 6 months

what is neuropathic pain

pain caused by lesion or disease affecting somatosensory system

what are the 2 types of neuropathic pain

• Central neuropathic pain (CNS lesions/disease)

• Peripheral neuropathic pain (PNS lesions/disease)

why does nociceptive pain usually have identifiable location

because nociceptors are activated at specific tissue sites producing localised signalling

what abnormal sensations can occur in neuropathic pain

• dysesthesia (abnormal sensation)

• allodynia (pain from non-painful stimuli)

• hyperalgesia (increased response to painful stimuli)

what are the typical neuropathic pain symptoms

• shooting

• stabbing

• burning or coldness

• pins and needles

• itching 

• chronic anxiety or depression

what are common causes of neuropathic pain

• Trigeminal neuralgia

• Pain following shingles (postherpetic neuralgia)

• Diabetic neuropathy

• Phantom limb pain following an amputation.

• Multiple sclerosis.

• Pain following chemotherapy.

• HIV infection.

• Alcoholism.

• Cancer.

• Atypical facial pain.

• Pain following a stroke or spinal cord injury

• Trauma Post-surgical pain

why can chemotherapy cause neuropathic pain

neurotoxic agents damage peripheral nerves

how can trauma or surgery lead to neuropathic pain

nerve damage → abnormal regeneration and sensitisation

what do nociceptors detect

• heat (via TRPVI channels)

• cold temps

• pressure

• chemical signals released during tissue damage (H_, ATP, bradykinin, prostaglandins etc)

• tissue damage

how are heat stimuli detected

through TRP channel activation (TRPV1/VR1 and VRL-1)

why does capsaicin (chemical found in peppers that make them spicy) feel hot

it activates TRPV1 receptors, the same channels triggered by heat

what are the 3 sensory fibre types and what do they detect

• Aβ – touch/pressure (large, fast)

• Aδ – sharp fast pain (medium)

• C fibres – slow, dull, burning pain (small, slow)

why is C-fibre pain slow and dull

because C fibres are unmyelinated with very slow conduction speeds (0.5-2m/s)

what do nociceptors do

create electrical signals and send them along nerves to spinal cord

peripheral sensitisation

next few flashcards

what substances are released during tissue injury

• bradykinin

• histamine

• ATP

• H+

• prostaglandins

• 5-HT

how do these chemicals cause sensitisation

they lower threshold of nociceptors, making them more responsive

why does NGF contribute to pain

it increases expression of pain receptors (e.g., TRPV1) and sodium channels

what are the 3 main ascending pathways

• Spinothalamic tract – fast pain → thalamus

• Spinoreticular tract – slow pain → reticular formation

• Spinotectal tract – reflex & emotional responses → PAG, limbic system

why is spinothalamic tract important

it conveys location and intensity of pain to cortex

how does spinoreticular pathway affect the pain experience

it contributes to suffering, arousal, and emotional response

where do nociceptive fibres first synapse

in dorsal horn of spinal cord

how does dorsal horn modulate pain

through excitatory projection neurons and inhibitory interneurons

why is the dorsal horn a key site for pain modulation

it is where peripheral signals can be amplified or suppressed before reaching brain

what is the Gate Control Theory

pain transmission is modulated by the balance of large-fibre (Aβ) and small-fibre (Aδ/C) inputs

how do large fibres (Aβ) affect the gate

their activation closes the gate → inhibits pain

how do small fibres (Aδ/C) affect the gate

their activation opens the gate → pain transmitted

why does rubbing injury reduce pain

rubbing activates Aβ fibres → closes the gate at the dorsal horn

how does TENS (transcutaneous electrical nerve stimulation) work

by stimulating large fibres to close the gate and inhibit pain signalling

what brain regions control descending pain inhibition

PAG → nucleus raphe magnus → spinal cord

which neurotransmitter mediates descending pain control

serotonin (5-HT) and endogenous opioids

how do descending opioids reduce pain

• Inhibit neurotransmitter release from C and Aδ fibres

• Activate inhibitory interneurons

• Reduce projection neuron firing

why is descending system important

explains how mood, stress, and expectation strongly modify pain perception

how does peripheral sensitisation contribute to neuropathic pain

• Cytokines increase nociceptor sensitivity

• TRPV1 phosphorylation makes heat receptors hyperactive

• Sympathetic sprouting causes abnormal firing

• More sodium channels increase spontaneous firing

what is ‘wind-up’ and why does it happen

repetitive C-fibre activation → cumulative depolarisation → progressively increasing pain

how does glutamate contribute to neuropathic pain

• Overactivation of NMDA receptors

• Reduced glutamate uptake → chronic excitability

how do supraspinal changes worsen neuropathic pain

• Cortical remapping enhances pain circuits

• 5-HT becomes excitatory instead of inhibitory

• GABAergic inhibition is reduced

• Fewer opioid receptors → opioids become less effective

what pharmacological options treat acute pain

• NSAIDs

• Opiates

• Local anaesthetics

how do NSAIDs reduce pain

by blocking prostaglandin synthesis (less peripheral sensitisation)

how do local anaesthetics block pain

they inhibit voltage-gated sodium channels → block action potentials

why do opioids often fail for neuropathic pain

due to reduced opioid receptor expression and central sensitisation

what types of drugs typically inhibit neuropathic pain

• anticonvulsants

• antidepressants

• topic agents