Pain management should ideally measure symptoms and treat pain mechanisms. But the identification of the underlying mechanisms is difficult as symptoms are not always equivalent to the mechanism.1
Usually, pain patients are analyzed on the basis of common causes of disease. This approach groups patients into categories, e.g. (low) back pain or osteoarthritic pain. Although such an approach is helpful, it ignores the possibility that diverse mechanisms may underlie the pain.Mechanism-based pain diagnosis can be difficult, but physicians should attempt to define the types of pain that the patient is experiencing:
Pain is not a homogeneous sensory entity, it is individual.
Primary types of pain include:
Pain can be caused by multiple, different mechanisms, and pain is processed and modulated by multiple excitatory and inhibitory systems.
Better understanding of pain mechanisms is important:
Analgesia may be obtained by drugs that either:
The analgesic potency of classical opioids in pain with a neuropathic component might be limited due to pathophysiological mechanisms.1
Sustained or repeated activation of the opioidergic system may lead to reduced opioid responsiveness and relative opioid analgesic tolerance.1
Therefore larger doses may are required to treat neuropathic pain than are needed to treat nociceptive pain. Higher doses, however, carry the risk of starting the Vicious Circle.2,3
The combination of classical opioids with co-analgesics is common for the pharmacological treatment of severe chronic pain conditions composed of both a nociceptive and a neuropathic component. However, there is still limited evidence for evaluation of benefits, and the risk of interaction and substance-specific side effects might be a limiting factor for combining two different substances:
Combination of different pharmacological agents are common and can either serve the purpose of addressing different underlying mechanisms or prevent / reduce side effects.Examples of fixed drug combinations include:
Two pain modulation systems are relevant in chronic pain.
Simultaneous activation of both systems may result in analgesic synergy.1
Based on the relevance of these two pain modulating systems, there is a clear rational for the development of analgesic combining the two mechanisms of action, μ-opioid receptor agonism (MOR) and noradrenaline reuptake inhibition (NRI), which enhance the concentration of noradrenalin (NA) in synaptic cleft, thereby enhancing NA-mediated effects.
A new pharmacological drug class – MOR-NRI – reflects the unique pharmacological profile differentiating this compound from all other centrally acting analgesics: