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• W2054883586 startingPage "131" @default.
• W2054883586 abstract "Multiple pathological mechanisms at multiple sensory sites may underlie the pain that follows nerve injury. This provides a basis for recommending more than one agent, either sequentially or in combination, for its treatment. According to this premise, new drugs that combine different mechanisms of analgesic action in a single molecule are gaining momentum, such as tapentadol which stimulates mu-opioid receptors (MOR) and acts as a noradrenaline reuptake inhibitor (NRI) in the CNS. Tapentadol is currently indicated for treating moderate to severe acute and severe chronic pain, and here we demonstrate its efficacy in an animal model of ongoing neuropathic pain. In particular, we performed a series of in vivo electrophysiological tests in spinal nerve ligated and sham-operated rats to show that systemic tapentadol (1 and 5 mg/kg) dose-dependently reduced evoked responses of spinal dorsal horn neurones to a range of peripheral stimuli, including brush, punctate mechanical and thermal stimuli. Furthermore, we showed that spinal application of the selective α2-adrenoceptor antagonist atipamezole, or alternatively the mu-opioid receptor antagonist naloxone, produced near complete reversal of tapentadol's inhibitory effects, which suggests not only that the spinal cord is the key site of tapentadol's actions, but also that no pharmacology other than MOR-NRI is involved in its analgesia. Moreover, according to the extent that the antagonists reversed tapentadol's inhibitions in sham and SNL rats, we suggest that there may be a shift from predominant opioid inhibitory mechanisms in control animals, to predominant noradrenergic inhibition in neuropathic animals." @default.
• W2054883586 created "2016-06-24" @default.
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• W2054883586 date "2011-01-01" @default.
• W2054883586 modified "2023-09-24" @default.
• W2054883586 title "Mu-opioid and noradrenergic α2-adrenoceptor contributions to the effects of tapentadol on spinal electrophysiological measures of nociception in nerve-injured rats" @default.
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• W2054883586 doi "https://doi.org/10.1016/j.pain.2010.10.004" @default.
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