• R Pellicano and L Guerra.
• Department of Gastroenterology and Hepatology, Molinette Hospital, Turin, Italy. rinaldo_pellican@hotmail.com
• Minerva Med. 2012 Dec 1;103(6):525-31.

AbstractChronic or acute pain related to skin ulcers or their management (medication, debridement) is a typical case of mixed pain, both neuropathic and nociceptive. It represents a disabling clinical condition that deteriorates the patient's quality of life. The pharmaceutical therapy must be based on both, intensity and the type of pain. Although NSAIDs, Non Steroidal Anti-Inflammatory Drugs are notoriously effective on nociceptive pain, do not give great results on neuropathic and mixed pain. Also the consumption of NSAIDs is affected by a series of side effects that may involve several organs. In case of neuropathic pain, the benefit deriving from the use of a single active principle is relative. This sets the rational grounds for the use of combined drugs. The paracetamol/tramadol combination represents an innovative solution in the treatment of both the neuropathic and nociceptive components of the pain, since both active principles have a different action mechanism, multiple targets and different pharmacokinetics. It is very interesting, from the clinical point of view, that tramadol is a pure antagonist, not selective, of µ, δ, and κ receptors and carries out and important inhibition action of serotonin and norepinephrine reuptake. This double mechanism, opioid and non-opioid, explains its analgesic efficacy also on neuropathic pain. Besides, since its opioid action is rather weak, it does not induce the severe side effects typical of traditional opioids. The benefit of such combination comes from their complementary pharmacokinetic profile, since the first has a quick action insurgence, while tramadol has a more prolonged effect. Therefore, this combination allows to obtain a quick and long lasting effect with a high tolerability profile also when treating skin ulcer pain.

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