The Physiology of Pain Flashcards
Nociceptive afferents synapse with interneurons, nociceptive projection cells and wide dynamic range cells in which laminae of the spinal cord?
Laminae I, II and V of the dorsal horn
(Dorsal horn = I-VI)
The axons of nociceptive projection cells, second order neurons, cross the midline and ascend via which two main pathways?
- Lateral pathways - which includes the neospinothalamic tract
- Medial pathways - includes the paleospinothalamic, spinoreticular, spinomesenphalic and other pathways
Explain what is meant by hyperalgesia and allodynia.
- Hyperalgesia - damage to nociceptive pathways results in increased sensitivity to pain
- Allodynia - central sensitisation leading to a painful response to non-noxious stimuli such as touch
What is neurogenic pain?
- Pathological pain caused by abnormal function of the pain pathways.
- Pain may arise from within the nervous system itself and may occur in the absence of any noxious stimuli.
- Pain can become entirely independent of nociceptor activity and may persist long after tissue healing.
Which neurotransmitters are used by Aδ and C fibres?
- Aδ fibres - glutamate
- C fibres - glutamate, substance P, others
Explain the differences in rate of impulse conduction between Aδ and C fibres.
- Aδ fibres - small diameter, thinly myelinated
- C fibres - smaller, unmyelinated
- Thus C fibres have a slower conduction rate
Describe the course of the first, second and third order neurons in the lateral pain pathways.
- Nociceptor - cell body in dorsal root ganglion
- 1st synapse - laminae I, II, V of dorsal horn
- Nociceptive projection cell - axon crosses midline and ascends in neospinothalamic tract
- 2nd synapse in ventral posterolateral nucleus (VPL nucleus) of thalamus
- Third order neurons project to mainly primary somatosensory cortex (S1) via posterior limb of internal capsule
Describe how the course of the medial pain pathways differ from that of the lateral pain pathway.
- Second order neurons project to non-specific thalamic nuclei and the reticular formation, among other regions
- Third order neurons have diffuse cortical targets, but notably project to the anterior cingulate cortex and insula; these structures along with limbic areas such as hypothalamus and amygdala mediate the emotional and motivational responses to pain
Describe 2 descending pathways important in modulation of pain.
- Periaqueductal grey matter (PAG) projects to rostral ventrolateral medulla (RVLM) - the sympathetic control centre - which projects serotonergic and adrenergic axons to the dorsal horn.
- Pontine reticular formation projects serotonergic and adrenergic axons to the dorsal horn.
- In both of these pathways, the descending axons travel in the dorsolateral funiculus of the spinal cord.
- The serotonergic and adrenergic axons activate inhibitory GABAergic interneurons in the substantia gelatinosa - lamina II.
Most afferent fibres terminating in the substantia gelatinosa are of what type? What is the significance of this in the control of pain?
- C fibres - they mostly terminate in the substantia gelatinosa, which corresponds to lamina II.
- Inhibitory GABAergic interneurons of this region inhibit the ascending pain pathways via presynaptic and postsynaptic mechanisms.
- These interneurons are activated by descending 5-HTergic and NAergic fibres from the dorsolateral pontine tegmentum and RVLM
- Thus, these descending modulatory pathways mainly inhibit pain mediated by C-fibres.
Aside from releasing GABA, what is the other mechanism by which inhibitory interneurons in the substantia gelatinosa inhibit the ascending pain pathways?
- They also release various peptides that act on opioid receptors
- These opioid receptors are found on the presynaptic terminals of nociceptor afferents and on nociceptive projection cells
Explain why pain originating from the viscera presents as referred pain, using the heart as an example.
- Somatic nociceptor input is somatotopically organised; visceral nociceptor input is not
- Visceral nociceptors converge on nociceptive projection cells in the dorsal horn
- E.g. afferents from the heart enter at T1-T5 and excite projection cells that relay information from the overlying chest and left arm
- Activity from these visceral afferents is perceived as arising from the body surface
Why are antidepressants and anxiolytics sometimes used to treat chronic pain?
- Chronic pain may be associated with reduced inhibition in the dorsal horn
- Antidepressants enhance release of 5-HT from descending axons, contributing to increased inhibition by interneurons in the dorsal horn
- Anxiolytics such as benzodiazepines also enhance inhibition in the dorsal horn
Why is chronic pain often treated with anticonvulsants?
- Chronic pain is associated with long-term potentiation of ascending pain pathways
- Anticonvulsants block enhanced activity due to abnormal VgNa+ channels
- They also reduce transmitter release, particularly at potentiated synapses - thus they act preferentially on hypersensitive pain pathways
Describe the differences between nociceptive specific cells and wide dynamic range cells.
Nociceptive specific (or projection) cells:
- Respond to Aδ and C fibres
- Arise from laminae I and II
- Locally inhibited by GABA, glycine and opioid receptor mechanisms
- Descending inhibitory control by NA and 5-HT
Wide dynamic range cells:
- Respond to noxious and non-noxious stimuli via a frequency code
- Thus known as “touch afferents”
- Arise from lamina V
