Somatosensory pathways and pain

Receptors and transduction

• A receptor converts a stimulus into a local, graded depolarisation, the generator (receptor) potential. It does not propagate; if it reaches threshold at the first node it triggers action potentials, whose frequency codes intensity. More receptors are recruited as the stimulus grows; perceived intensity rises roughly with the logarithm of stimulus strength (Weber–Fechner).
• Adaptation: rapidly adapting (phasic) receptors signal change; slowly adapting (tonic) receptors signal a sustained stimulus. Nociceptors barely adapt and may sensitise.

• Thermal receptors: cold receptors (TRPM8, Aδ fibres) and warm receptors (C fibres). Above about 45 °C, tissue starts to be damaged and nociceptors with TRPV1 channels (the capsaicin receptor) fire: a hot pan is felt as burning pain, not warmth. Cold air triggers cough through airway irritant receptors.
• Two-point discrimination is about 2–3 mm on the fingertip but about 40 mm on the back, because fingertip receptors are dense with small receptive fields and large cortical representation. Lost two-point discrimination with preserved touch suggests a dorsal column or parietal lesion.

Nerve fibre types

Local anaesthetics block small fibres first (autonomic and pain before touch and motor). Pressure blocks large myelinated fibres first. Hypoxia affects B fibres first.

Ascending pathways

The homunculus places the leg medially (anterior cerebral artery) and the hand and face laterally (middle cerebral artery). After an amputation, the cortical map reorganises: the face area lies next to the hand area, so stroking the cheek is felt on the missing fingers, and phantom pain may follow; mirror therapy can help.

Lesion patterns

A stab wound with right leg weakness and loss of position sense, and loss of pain and temperature in the left leg and trunk from just below the umbilicus (T10), is a right hemisection near T10, a segment or two above the sensory level.

Pain mediators and modulation

• Tissue injury releases K⁺ and H⁺ from damaged cells, bradykinin (the most potent pain-producing substance), serotonin, histamine and ATP; prostaglandins (PGE₂) do not cause pain alone but sensitise nociceptors, which is why NSAIDs help. Ischaemic muscle pain during gripping with a cuff inflated comes from accumulated metabolites (K⁺, H⁺, bradykinin), not lactate alone.
• Fast pain (Aδ) uses glutamate; slow pain (C) uses glutamate and substance P.
• Gate control: large-fibre (Aβ) input excites inhibitory interneurones in the substantia gelatinosa (lamina II), damping pain transmission: rubbing a knock and TENS work this way. Similarly, scratching activates pain pathways whose interneurones inhibit itch neurones in the cord.
• Descending inhibition: periaqueductal grey to nucleus raphe magnus to the dorsal horn, using endorphins, enkephalins, serotonin and noradrenaline. Placebo analgesia is partly endogenous opioid release, reversed by naloxone.
• Opioids in the dorsal horn (intrathecal morphine): presynaptic mu receptors close Ca²⁺ channels on C-fibre terminals, reducing release of glutamate and substance P; postsynaptic receptors open K⁺ channels and hyperpolarise. Hydrophilic morphine spreads rostrally and can cause late respiratory depression.
• Hyperalgesia and allodynia follow peripheral and central sensitisation (NMDA receptors).

Visceral pain and pain-insensitive tissues

• Viscera are insensitive to cutting and burning; visceral pain comes from distension or stretch, ischaemia, chemical irritation and inflammation. It is dull and poorly localised.
• Brain tissue has no nociceptors: cutting the cortex is painless, but the dura, vessels and venous sinuses are pain-sensitive. Tumour headache comes from stretching these.

Referred pain

Visceral and somatic afferents converge on the same dorsal horn neurones, and the brain attributes pain to the familiar skin of that dermatome.

Neuropathic and abnormal pain

• Neuropathic pain (diabetic neuropathy, postherpetic neuralgia): amitriptyline, duloxetine, gabapentin, pregabalin. A capsaicin 8% patch overstimulates TRPV1 endings, then defunctionalises them for weeks.
• Trigeminal neuralgia: an arterial loop (superior cerebellar artery) compresses the root, causing focal demyelination, so impulses jump between bare axons (ephaptic transmission): electric-shock pains triggered by touch, with normal examination. Carbamazepine is first-line. In young adults or with sensory loss, think of MS or tumour.
• Complex regional pain syndrome after fracture and immobilisation: burning pain out of proportion, swelling, shiny skin, colour and temperature changes, stiffness. Early movement reduces risk.
• Traumatic neuroma: a painful nodule of regenerating axons in a scar after nerve section or amputation.
• Congenital insensitivity to pain: loss-of-function mutation of the Nav1.7 sodium channel on nociceptors; normal touch and temperature discrimination but no pain, with anosmia; injuries go unnoticed.
• Leprosy: Mycobacterium leprae grows best in cooler tissues, so it damages superficial nerves (ulnar at the elbow, common peroneal at the fibular neck) and cool skin (earlobes, forearms), sparing warm axillae, groins and scalp.

Remember Dorsal columns cross in the medulla, spinothalamic fibres in the cord; C fibres burn, Aδ fibres stab.

Exam trap Pacinian corpuscles sense vibration; Meissner corpuscles sense light touch; TRPV1 nociceptors sense heat above about 45 °C.

Exam trap Pain and temperature loss in a hemisection starts 1–2 segments below the lesion on the opposite side.

How FCPS asks about this

• Local graded depolarisation at a receptor: generator potential.
• Crossing of the dorsal column pathway: lower medulla; spinothalamic crosses in the cord.
• Why cardiac pain is felt in the left arm: convergence on T1–T4 dorsal horn neurones.
• Stimulus causing visceral pain: distension or stretch, not cutting or burning.
• Intrathecal morphine: less transmitter released from C-fibre terminals.
• Phantom fingers felt when the cheek is stroked: cortical map reorganisation.
• Most potent pain mediator: bradykinin; prostaglandins sensitise nociceptors.