A view on multimodal pain management

Chronic pain is complex physiologically and there are many influences on the pain experience. The approach to treatment therefore needs to be multimodal, often with a number of different interventions.

As yet, no “gold standard” has emerged for multimodal pain management for neuropathic pain. The various multimodal pain protocols that have been developed, however, share similar objectives, to reduce side effects, to reduce dose and to avoid and even to eliminate narcotics leading to troublesome side-effects while reducing the quality of life. Because pain involves multiple mechanisms that rely  on different receptor systems, it is beneficial to utilize  a multimodal approach to achieve pain relief in complex pain states such as neuropathic pain. 

The concept of multimodal  analgesic therapy was introduced to provide effective  pain relief, reduce opioid-related and other adverse effects, and improve clinical pain reduction by combining different classes of drugs with varying mechanisms of action to achieve additive or synergistic effects. Multimodal analgesic regimens in general have demonstrated improved efficacy with improved tolerability. The addition of the endogenous painkiller palmitoylethanolamide to classical analgesics such as tramadol and pregabalin has proven to reduce pain further, while decreasing side effects.

Palmitoylethanolamide has a very benign side effect profile, seems to have no renal clearance and drug-drug interactions have never been found so far. It is metabolized directly in the intracellular compartments of nerve cells and immune competent cells, as well as in glia. These cells all play a crucial role in chronic neuropathic pain.

Our advice is to combine classical analgesic regimes with this supplement, and start dosing 400 mg trice daily. As a rule of thumb the maximal dose is 30 mg/kg bodyweight. For central neuropathic painstates we advice to at least surpass the 1200 mg/day dose.


Multimodal pain treatment regimens are supported by numerous professional and regulatory organizations that have published guidelines for clinicians and institutions on the management of pain.

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