There is clear evidence from both preclinical and clinical studies that both peripheral and central hyperexcitability play important roles in determining the level of pain perceived. Rightly, much emphasis has been put on spinal cord mechanisms in central excitability but it now becoming clear that spinal excitability can be regulated by descending pathways from the brain. These originate from predominantly monoamine systems (noradrenaline and 5HT) which are additionally implicated in control of emotions, fear, anxiety, thermoregulation and the sleep cycle and so may mediate these pain induced co-morbidities. Much of the early work in this area concentrated on descending inhibitions, now known to be predominantly noradrenergic, and failure of descending inhibitions has been reported in patients as has their recruitment in placebo analgesia as well as the actions of anti-depressant drugs in pain. However, pain could equally be increased by enhanced descending facilitations and data is accumulating on exactly this. These excitatory influences are likely to contribute to the development and maintenance of central sensitisation in the spinal cord. Recent work shows altered descending excitatory controls in patients with severe pain from osteoarthritis.
These pathways form a link between emotional states and levels of pain, and may be one route by which coping and catastrophizing can alter the sensory components of pain at the level of the first relays. The levels of midbrain generated modulation, both positive and negative, may be a key factor in individual variations in pain and contribute to some “dysfunctional” pain states such as fibromyalgia.
Preclinical and early clinical investigations related to monoaminergic pain modulation.
Bannister K, Bee LA, Dickenson AH.
Neurotherapeutics. 2009 Oct;6(4):703-12.
Disclosure of Interest None Declared
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