08. Pain - Part 2 (Neurogenic Pain) Flashcards
What is neurogenic pain?
Pain occuring from damage to neurons
What is nocigenic pain?
Pain occuring from painful stimuli acting on nociceptors
Neurogenic pain: causes
- spontaneously discharging nociceptors
- or lack of inhibitory mechanisms
Neurogenic pain: examples
- shingles (caused by herpes zoster virus)
- phantom limb pain or amputated stump pain
- fibromyalgia
- trigeminal neuralgia
What is chronic pain?
Pain that lasts longer than 12 weeks, or beyond the natural healing time.
What peripheral mechanisms contribute to chronic pain?
- peripheral neuron sensitisation
- increased activity of damaged axons & sprouting
What central mechanisms contribute to chronic pain?
- hyperexcitability of central neurons
- reorganisation of synaptic connectivity in spinal cord
- disinhibition - removal of tonic descending inhibitory control
Mechanisms leading to chronic pain
- Nerve damage causes resprouting and new synapse formation in dorsal horn
- Ab fibers synapse onto nociceptive neurons
- Excess glutamate release during painful stimulus results in excitotoxicity, loss of inhibitory interneurons, no brake on excitation
How do we manage chronic pain?
- It’s very complex - there are often other problems to be solved (primary disease, depression, sleep disturbance, fatigue)
- 80% of depressed people have physical symptoms
- Drugs: tricyclic antidepressants, anticonvulsants, NMDA antagonists, cannabinoids
Perception of Pain
Everyone perceives pain differently
(therefore same injury may cause chronic pain in one patient but not another)
What can explain differences in pain sensitivity?
- Biological factors
- Gender
- Psychopathology
- Social factors
- Personality
- Cultural factors
- Situation and circumstance
- Beliefs about pain
What biological factors affect pain sensitivity?
- Genetics
- Disorders with genetic component (congenital pain disorders, migraine, temporomandibular joint disorder)
-Genetic variability in components of system (to increase levels of analgesic peptides (NPY), marked decline in GABAergic function, accentuated sympathetic responses) - Interactions with other systems (Irritable bowel syndrome - brain-gut dysfunction)
How does sex affect pain sensitivity?
- Some disorders associated with a particular sex (cluster headaches are male; migraine, TMJ, Rheumatoid Arthritis, Fibromyalgia are female)
- Pain perception (thresholds) differ with sex
What do female humans report about their pain?
- more intensive acute pain
- more chronic pain
- greater intensity
- pain in more bodily areas
- longer duration
Why are there sex differences in pain perception?
- Biological factors
- Genetic differences
- Sex hormones
- Brain imaging
- Psychosocial factors
- Negative emotion
- Coping strategies
- Social influences
Sex differences in opioidergic mechanisms
Females more sensitive to morphine (need less)
Sex differences: What does mu opioid receptor show?
- females may show less endogenous analgesic effects
- differential distribution and activation of receptors in male/females
Sex differences: what does the kappa opioid receptor show?
Kappa opioid receptor agonists have stronger analgesic effects in females
- mediated by melanocortin-1 receptor (Mc1r) (also involved in regulating skin and hair colour)
- women with the Mc1r-2 allele (associated with red hair and fair skin) display greater analgesic response than men with same allele or females with other variants
