Pain Flashcards
What are the types of pain?
• Somatic - cutaneous, i.e. body surface (sharp and burning sensation), deep tissues, i.e. musculoskeletal tissues (dull or aching but localized sensation)
• Visceral - originates from organ tissues of the thorax, abdomen or pelvis (deep, dull and vague sensation)
^^ the above two are nociceptive pain (detecting DAMAGE to TISSUE)
• Neuropathic - caused by lesions of the nervous system, resulting in structural damage to the nervous units, rather than by receptor stimulation (burning/stabbing sensation). Here, there may be no damage to the tissue.
○ Can be caused by anti-cancer drugs, e.g. those that inhibit microtubule formation. These would also stop axons from.
• Migraine- a severe headache usually affecting only one side of the head
• Phantom - sensations of burning, tingling felt in absent limb
Referred pain is pain experienced from a site distant from injury. These can be split into 2 main types, nociceptive pain and neuropathic pain:
• If neurone is damaged, it is neuropathic pain* (Neuropathic pain can also be caused by drugs e.g. taxol; infection e.g. HIV; diabetes)
• If it is in tact and detects pain, it is nociceptive pain
What stimuli can cause pain?
- Temperature - heat, cold
- Mechanical - pressure, friction oedema
- Chemical - gastric enzymes, histamines, caustic substances
What is acute v.s. chronic pain?
- Acute Pain: Sudden, self-limiting, <6 months, precipitous event, responds well to treatment, obvious symptoms (restless, anxious, crying).
- Chronic Pain: Sudden or gradual, with periods of remission and exacerbation, >6 months, may be no stimuli/ not associated with injury.
Describe the anatomical pathways of pain perception
Here the first order neurones are called the dorsal root ganglia (DRG) neurones because their cell bodies lie in the DRG. The nociceptors are the peripheral nerve endings of these axons, which synapse in the substantia gelatinosa of the dorsal horn of the spinal cord. Second order neurones from the nucleus proprius (principal sensory nucleus) called principle sensory neurones, decussate in the anterior white commissure, to then form the (neo)spinothalamic tract. The tracts (anterior and lateral spinothalamic) ascend through the brainstem and ends in the thalamus (ventral posterolateral nucleus and posterior nuclei of the thalamus). Axons of the thalamus then project to the primary somatosensory cortex.
Dorsal root ganglia control sensation to all the body except the head, which is controlled by trigeminal ganglion.
What chemical signals do nociceptive neurones respond to?
Nociceptive neurons respond to the chemical signals of: -Substance P -Histamine -Serotonin -Bradykinin Prostaglandins -NGF
Describe the speed, diameter, myelination and function of the three types of neurones in the DRG
There are 3 types of neurones in dorsal root ganglion, separated by diameter and myelination:
• Small Diameter, unmyelinated C-Fibres (Chronic Pain) 0.5-2 m/s (2 mph)
• Medium Diameter, thinly myelinated A-delta Fibres (Acute Pain) 5-35 m/s (40 mph)
• Large Diameter, myelinated, A-beta Fibres (Touch) 35-75 m/s (240 mph)
Describe the gate-theory of pain
Activation of A-beta fibres can block the signals transmitted by A-delta and C fibres. A-beta fibres send information about pressure and touch that reach the spinal cord and brain to override pain messages carried by A-delta and C-fibres.
A-beta fibres are very fast, C-fibres are much slower (due to myelination and axon diameter. This difference in speed is key. This is why when you get an injury/bump, you rub it to make it feel less worse – this is gate control theory in practice in daily life.
Describe the organisation of the spinal chord layers
The grey matter of the spinal cord are arranged in layers or laminae,
• Six in the dorsal horn (I-VI),
• Three in the ventral horn (VII-IX)
• A column of cells clustered around the central canal as Lamina X
Where do DRG neurones terminate in the dorsal horn?
- C-fibres nociceptive afferents terminate mainly in Laminae I and II
- A-delta afferents terminate mainly in Laminae I, II and V
- A-beta afferents terminate mainly in Laminae V, VI
What are the major brain areas involved in the pain pathways?
- S I: the primary sensory cortex
- S II: the secondary sensory cortex
- The anterior part of the insula
- The cingulate gyrus
What are the kinds of molecular pain inducers?
- Bradykinin
- Protanoids
- Nerve Growth Factor (NGF)
Describe how bradykinin causes it’s effects.
Bradykinin binds to B1&B2 Receptors, which are 7-TM G-protein coupled receptors linked to Gq and Gi. This then activates phospholipase Cβ (PLCβ) and phospholipase A2 (PLA2).
• Activation of PLCβ leads to protein kinase C (PKC) activation
• Activation of PLA2 causes production of arachidonic acid (AA) from the cellular phospholipid bilayer. AA is converted into prostanoids
Bradykinin itself can also cause pain through binding of B1 and B2 receptors.
When is bradykinin released?
Bradykinin is a polypeptide (Arg-Pro-Gly-Phe-Ser-Pro-Phe-Arg) made from Kininogen by proteolysis in blood, usually in response to tissue damage/blood coagulation.
When/how are prostoglanding released?
Prostaglandin (PGE2) are synthesised/released from granulocyte, Macrophage, and Nociceptive Neurons in response to tissue damage.
Describe how prostoglanding causes it’s effects.
Prostaglandin Receptors are (DP1, DP2/EP1, EP2, EP3, EP4/FP/IP) 7-TM G-protein coupled receptors. PGE2 binds to EP2 receptor expressed at free nerve endings. This activates adenyl cyclase via Gs –> increased cAMP –> PKA activation. PKA phosphorylates channels and lowers the threshold of nociceptive neurones.
