Neuropathic pain (NP) is an enormous burden for patients, caregivers and society. NP is a pain state that may develop after injury of the peripheral or central nervous system because of a wide range of diseases and traumas. A NP symptom component can be found also in several types of chronic pain. Many NP patients are substantially disabled for years. Due to its chronicity, severity and unpredictability, NP is difficult to treat. Tapentadol is a central-acting oral analgesic with combined opioid and noradrenergic properties, which make it potentially suitable for a wide range of pain conditions, particularly whenever a NP component is present or cannot be excluded. In randomized controlled trials, tapentadol has proved to be effective in relieving NP in diabetic peripheral neuropathy and in chronic low back pain. In observational studies, tapentadol reduced NP in chemotherapy-induced peripheral neuropathies, blood and solid cancers, and the NP component in neck pain and Parkinson’s disease. This narrative review aims to provide clinicians with a broad overview of tapentadol effects on NP.

Thanks to the progress in early diagnosis and treatment of cancer, the life expectancy of cancer patients has now increased. Patients are, therefore, more likely to experience their individual cancer pain as a chronic pain. As a consequence, long-term treatment of cancer-related pain and oncological therapy-related pain are a major need for all patients and a challenge to all healthcare professionals. Tapentadol is a centrally acting analgesic drug characterized by two synergistic mechanisms of action, since it acts at the µ-opioid receptor (MOR) and inhibits noradrenalin re-uptake (NRI). Therefore, tapentadol has been considered the first of a new class of drugs, MOR-NRI. Tapentadol has been tested in different populations of cancer patients (opioid-naive and -pretreated), such as those with pain of mixed etiology, patients with pain from hematological malignancies and patients experiencing pain conditions due to anticancer treatment. According to available evidence, tapentadol prolonged release was well tolerated and effective in cancer pain patients. In randomized, double-blind and active-controlled trials it proved non-inferior to standard opioids like morphine or oxycodone in the management of moderate-to-severe cancer pain, both in opioid-naive and in opioid-pretreated patients. The good analgesic efficacy may be partly due to the action of tapentadol on neuropathic pain components. Together with the low rate of gastrointestinal adverse effects and the overall favorable safety profile, tapentadol can be considered a good option in cancer pain patients, who can suffer frequently from nausea, vomiting, constipation or other events that further reduce their quality of life.

Immunomodulatory effects of endogenous and exogenous cannabinoids have been investigated in numerous studies, mostly performed with isolated cells or transformed cell lines, but only sparse data exist on human polymorphonuclear neutrophils (PMNs). We therefore investigated the respiratory burst reaction of human whole-blood PMNs under the influence of cannabinoids using flow cytometry. In their natural whole-blood milieu, a CB₂ receptor-dependent stimulation of the PMN respiratory burst was found at nanomolar concentrations of CP55 940 [(-)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-trans-4-(3-hydroxypropyl)cyclohexanol] and methanandamide after a 3-h incubation period, whereas the short-living and rapidly hydrolyzed endogenous ligand anandamide did not alter the burst reaction of whole-blood PMNs under the same experimental conditions. The stimulatory cannabinoid effect was totally absent in isolated PMNs but could be transferred onto isolated PMNs by adding the cell-free low-molecular mass plasma fraction (<5000 Da) of cannabinoid-incubated blood, indicating an indirect mechanism depending on humoral products or mediators. Results of our further experiments suggest that products of the arachidonic acid metabolism are mediators of the cannabinoid-induced enhancement of the respiratory burst reaction of whole-blood PMNs.