Compared to acute pain with its distinct warning and protective function, chronic pain has lost its direct relationship to the triggering event and has become a disease in its own right.
Pain can however persist long after its usefulness as an alarm system and after tissue damage has healed.
Such chronic pain is probably not directly related to initial injury or disease but is secondary to physiological changes in pain signalling and detection.1,2
Poorly managed acute pain can lead to chronic pain states.
If pain is not treated adequately at an early stage, it often becomes more difficult to treat.
Pain lasting longer than 6 months is a burden for the patient and is not to be underestimated; it represents a special therapeutic challenge for the physician.
Chronic pain, a history of pain-associated surgeries and low social support are negative predictors for treatment outcome1.
Over time, chronic pain leads to morphological changes in the central nervous system2,3.
A number of mechanisms are involved in the sensitisation of pain:
During peripheral sensitisation1-4:
Sensitisation, activation of silent neurons and neurogenic inflammation amplify the effects of nociceptive stimuli.
A tangible results is, for example, hyperalgesia, i.e. painful stimuli are perceived more intensely. Allodynia, i.e. normally non-painful stimuli, such as pressure stimuli, are experienced as pain.
Persistently, painful stimuli cause excessive excitation of spinal and supraspinal neurons (central sensitisation).1-3
These sensitisation processes increase the spontaneous activity and stimulus responses of the central neurons.
The μ-opioid receptor system and the monoaminergic system are highly relevant in the modulation of pain. Both play a key role in ascending and descending pain pathways.
μ-opioid receptor system
μ-opioid receptor agonists influence and directly inhibit the transmission of pain signals via the ascending pathway. In addition, μ-opioid receptor agonists are also involved in the modulation of pain signals on a supraspinal level with modulating impact on the descending pathways.
Key players of the monoaminergic systems are noradrenaline (NA) and serotonin (5-HT):
In acute nociceptive pain, pain modulation is to a large extend regulated by the opioidergic system (A).
In chronic pain (often associated with neuropathic components) modulations to the opiodergic system can lead to a reduction of opioid responsiveness (e.g. analgesic tolerance and/or opioid-induced hyperalgesia).1,2
A reduced activity of the opioidergic system means that the relative contribution of the two pain inhibiting systems changes towards the monoaminergic system (B), with noradrenaline mediated pain inhibition being of particular relevance.3